repro phys final

• ABO incompatibility

- A fetus can also suffer from ABO incompatibility with the mother • When the mother has blood type O and the fetus is type A or B • If the fetus's red blood cells cross the placenta during pregnancy or at delivery, the mother's immune system will make antibodies that can destroy the fetus's or newborn's red blood cells • Although most ABO incompatibility infants have mild or no symptoms, some newborns may suffer serious jaundice or swelling, and a blood transfusion may be necessary to save the infant's life

Use of the Combination • Major side effects

- Because breast cancer is the most common cancer in women, and because many breast cancers are estrogen responsive, several large studies have asked whether combined oral contraceptives increase the risk of breast cancer • Some of the studies found no association between COC use and breast cancer; others found a slight increased risk that disappears 5-10 years after • A worldwide analysis of 54 studies involving 150,000 women found a slightly elevated risk of breast cancer in oral contraceptive users; this risk disappeared 10 years after pill use was discontinued • A meta-analysis published in 2006 found a small increased risk only in women who had given birth • The large, long- running Nurse's Health Study in the US found no increased breast cancer risk among current or former oral contraceptive users • The Women's Contraceptive and Reproductive Experiences (Women's CARE) study similarly found no overall increased risk • Long-term use (five years or more) of the combination pill increases the risk of cervical cancer • This risk decreases when women discontinue use of the pill • Finally, there is evidence that combination pill use may slightly increase the risk of both benign and cancerous liver tumors • Despite these increased risks, the overall death rate from cancer does not differ between oral contraceptive users and nonusers, as COC use protects against ovarian and endometrial cancers • Studies of the cardiovascular effects of the birth control pill have also yielded mixed results • Use of the combination birth control pill can pose a risk to women who are predisposed to cardiovascular disease - This is the most serious potential complication of pill use - Cardiovascular disease can lead to deaths from heart attacks, blood clots in the lungs (pulmonary embolism), or bursting of a blood vessel in the brain (cerebral hemorrhage) - Two of the rare but serious side effects of the combination pill are hypertension (a rise in blood pressure) and increased risk of blood clots in the legs, heart, lungs, and brain • Women who have a history of blood clots or vein inflammation, a history of heart disease or stroke, or those who have uncontrolled high blood pressure should not be on the pill • Some evidence suggests that the combination pill can raise the levels of triglycerides and cholesterol in the blood • Side effects of the pill related to cardiovascular disease were more pronounced in the early birth control pill formulations; they are now less of a concern with the newer, lower-dosage pills • However, smoking cigarettes, especially in women over 35, greatly increases adverse cardiovascular effects in users of birth control pills - Despite warnings on pill containers about smoking and pill use, approximately 30-40% of women in the US who take the combination pill also smoke - The steroid hormones in the pill enter breast milk, but there is no evidence that consumption of these steroids by the infant harms its development • A lactating woman should not take the combination pill because it suppresses milk production • Although there is no evidence that taking the combination pill before or during the first few days of an unknown pregnancy harms the fetus, pregnant women should avoid use of the combination pill - Because of the potential minor and serious adverse side effects of the combination pill, women should consider some other contraceptive measure if they smoke or have a history of blood clotting, liver disease, high blood pressure, epilepsy, diabetes, heart attack, or stroke

• High Altitude

- Carrying a pregnancy at an altitude greater than 8000 feet can increase risks to both the mother and the fetus - Babies born at high altitude weigh about two-thirds of a pound less on average than babies born at sea level - Furthermore, there is an increased incidence of severe jaundice and neonatal fatality - High blood pressure (hypertension) is also more common in pregnant women at high altitude - If the mother smokes, all of these risks are increased two to three times

Bacterial STDs • Gonorrhea

- Gonorrhea is an STD that has been afflicting humans for centuries • The frequency of gonorrhea in the US exhibited an epidemic increase that peaked in the late 1970s and then decreased until 1997 • Since then, the incidence has remained fairly stable • Currently, more than 300,000 new gonorrhea cases are reported each year in the US • This is an underestimate of the actual extent of the disease in the United States because fewer than half of all cases are reported; the CDC estimates that about 820,000 new cases actually occur each year (Fig.17.1) • The incidence of gonorrhea is especially high in three groups: sexually active individuals younger than 24 years of age, blacks, and MSM, especially those who live in high-density urban areas and who have unprotected sex with multiple partners • About 70% of new cases occur in the 15-to 24-year-old group - Causes of Gonorrhea • Gonorrhea is caused by the bacterium Neisseria gonorrhoeae, named after the scientist Albert Neisser, who identified it in 1879 • N. gonorrhoeae is a gram-negative, diplococcus bacterium • Diplococcus means that these bacteria occur in pairs, with their adjacent sides flattened - A common name for the bacterium N. gonorrhoeae is gonococcus, and gonorrhea is often referred to as a gonococcal infection • In 1883, Christian Gram of Denmark invented a stain that differentiated gram-positive from gram-negative bacteria - Gram-positive bacteria stain more darkly because of differences in their cell wall structure - For decades, gonorrhea was detected by staining a urine sample or vaginal secretion, then examining it under the microscope - Sometimes the sample would have to be cultured for several days to grow sufficient amounts of bacteria before staining • Newer PCR based DNA methods are replacing culture and staining techniques - Transmission- The gonorrhea bacteria thrive in the moist membranes of the urogenital tract, as well as in the mouth and oral cavity, anus, and eyes • The main way this bacterium is transmitted is during vaginal, oral or anal sexual contact • Consistent use of a condom during vaginal or anal coitus greatly reduces the risk of transmission of the disease • A pregnant woman can also transmit gonorrhea to her infant as it passes through the birth canal • There are several different strains of N.gonorrhoeae, some more damaging than others • Once bacteria infect a person, the incubation period (the time it takes before symptoms appear) is usually 2- 5 days, but it can be as little as 1 day or as long as 8 days - Symptoms for Females • Most females who acquire gonorrhea are asymptomatic • When present, symptoms are often mild or nonspecific and can easily be mistaken for another type of vaginal infection or a bladder infection • This presents a problem because undiagnosed women are carriers of the disease without knowing it, and the disease can reach an advanced stage before a female knows that she has been infected • In women who exhibit symptoms, the first sign usually is the appearance of a clear or whitish fluid discharge from the vagina (infection or inflammation of the vagina, called vaginitis) • This discharge soon changes to a yellowish or greenish color— that is, it becomes a purulent discharge (a pus-filled discharge) • The vaginal wall can become quite irritated at this time and bleeding may occur, especially during vaginal intercourse - Symptoms in Females • Eventually, the infection can reach the cervix; infection and inflammation of this organ (cervicitis) contribute to the purulent discharge • A discharge can also come from the urethra (urethritis) • Urination can become difficult and painful with urethritis • Also, the bacteria can reach the urinary bladder, causing infection • Because symptoms such as vaginitis and urinary tract infection can have other causes, women with a gonorrheal infection can be misdiagnosed • Screening is an important method for early detection of gonorrhea • CDC recommends yearly gonorrhea testing for all at- risk sexually active women (those who have new or multiple sex partners, or who live in areas with high rates of infection), and at least yearly screening for at -risk men (gay and bisexual men) - Complications in Females • If left untreated, the bacteria can infect the uterus (endometritis) and can reach the oviducts 2-10 weeks after the initial infection • Inflammation and infection of the oviducts can lead to infertility • The bacteria can spread to other pelvic and abdominal organs, resulting in a dangerous condition called pelvic inflammatory disease • The bacteria can also enter the bloodstream and cause inflammation of the heart, brain, spinal cord membranes, eyes, skin, and joints • Oral coitus with a person carrying the bacteria in his or her genital region can lead to infection of the oral cavity • Anal coitus can transmit the disease into the anus and cause inflammation of the rectum (proctitis) • Both women and men infected with gonorrhea are more likely to acquire HIV infection and to transmit HIV to their sexual partners - Symptoms in Males • Most men (about 90%) develop recognizable symptoms of gonorrhea, although in some the symptoms are mild • Usually symptoms appear within two weeks of infection, but may take as long as 30 days to appear • The first signs usually are a purulent discharge from the urethra and redness of the glans of the penis • Urination can become painful and difficult, and scar tissue can form in the urethra • Men can also have painful erections, pain in the groin region, and a low fever • If not treated, the infection can spread in about three weeks to the urinary bladder and prostate gland and can infect these organs • The epididymes also can become infected, and in some cases, the testes themselves become infected and inflamed (orchitis), sometimes leading to infertility - Symptoms in Males • The symptoms of gonorrhea are not especially useful in diagnosing the disease - Symptoms are similar to thoise of some other kinds of STDs - Four out of five females and one in 10 males are asymptomatic • No reliable blood test for gonorrhea • A sample of the discharge from the penis or cervix can be stained for microscopic observation • This reveals the organisms only in about half of infected women, although the test is more accurate for men • Alternatively, swabs of the urethra, cervix, and/or rectum can be made and cultured in a special (Thayer-Martin) medium • The colonies of bacteria growing in this medium are then examined with a microscope for the presence of N. gonorrhoeae, and several biochemical tests are used to confirm the presence of this organism • This culture test takes about 24-48h - Symptoms in Males • Unfortunately, in about 15-20% of people who have the disease, gonorrhea bacteria are not visible in a culture • Therefore, it is a good idea to have repeat cultures done • Newer tests can detect the genetic material of gonococcus bacteria - Treatment • Treatment with an injection of penicillin has been the standard medication for gonorrhea since the 1940s • However, strains of N. gonorrhoeae have appeared that produce an enzyme (penicillinase) that destroys penicillin. These penicillin- resistant strains, called ―super gonorrhea,‖ are becoming more common in the US and produce fewer and milder early symptoms • With the alarming increase in penicillin - resistant strains, the CDC stopped recommending penicillin as the treatment of choice for this disease • Instead, since 1993, it has recommended the use of fluoroquinolones (i.e. ciprofloxacin, ofloxacin, or levofloxacin) for treatment of the disease • However, fluoroquinolone - resistant N. gonorrhoeae have been found recently in people who had been infected in Asia, the Pacific Islands, and California - Treatment • In 2004, the CDC recommended that fluoroquinolones no longer be used to treat these gonorrhea cases • The list of alternative antibiotics for these patients is limited, and treatment often is in the form of an injection rather than oral medication

Hormones and Birth • Prostaglandins and Oxytocin

- In response to the changing E/P ratio in the maternal blood, other hormonal factors participate in initiating or maintaining human labor • Prostaglandins are a group of fatty acids widely distributed in various tissues • Some prostaglandins stimulate the contraction of uterine muscles and now are used by physicians to induce labor at term • A high E/P ratio in the mother's blood appears to enhance the production of prostaglandins by the uterus, as does uterine contraction itself (positive feedback) • We know that prostaglandin levels increase in the mother's blood a month before delivery and are very high during labor, with bursts in secretion 15- 45s after each uterine contraction • Levels of prostaglandin in the amniotic fluid increase during labor • Certain drugs (such as aspirin) inhibit the synthesis of prostaglandins, and these drugs may delay labor by a few days if given routinely near term - It has long been known that a hormone secreted by the posterior lobe of the pituitary gland stimulates the contraction of uterine muscle • This hormone, oxytocin (in Greek, meaning "quick birth"), also appears to be involved in human birth • A synthetic oxytocin (e.g.pitocin) is often used by physicians to induce labor contractions • Mechanical stimulation of the vagina, cervix, or uterus causes release of oxytocin; this reaction is called the fetal ejection reflex • Once oxytocin is secreted, it increases the intensity of uterine contractions, which in turn causes more oxytocin release, yet another example of positive feedback during human birth • Recent research suggests that the placenta itself secretes oxytocin and that it is placental oxytocin, rather than pituitary oxytocin, that initiates labor • In women, oxytocin levels in the blood are moderately low in the first stage of labor • Although oxytocin is low at the time of labor initiation, the number of oxytocin receptors in the uterus increases due to the increase in the E/P ratio in the woman's blood • The levels of circulating oxytocin are higher and more variable in the second stage • This hormone may simply increase the intensity of uterine contractions during later stages of labor • Oxytocin-induced contractions of the uterus cause the release of prostaglandins from the uterus, further escalating the contractions • Thus, oxytocin may promote labor both directly and indirectly • We still have much to learn about the hormonal initiation of labor in humans • Three hormonal positive feedback loops have been identified that, once set in motion, disrupt the quiescence of the uterus that was necessary to support pregnancy for the previous nine months • The onset of labor appears to be driven by an increase in stress hormones from the mother and/or fetus • Rising CRH from the placenta upregulates fetal production of cortisol, which itself increases placental CRH; this is the first positive feedback loop • The other two feedback loops involve prostaglandins and oxytocin, hormones that cause uterine contractions, and those contractions in turn upregulate release of the hormones • These feedback loops intersect with one another, amplifying the hormonal induction of • Recent studies have focused on the role of inflammation in human parturition • Just before or during labor, white blood cells invade the uterus, cervix, and fetal membranes, and there is an increase in production of proinflammatory molecules called cytokines

Female Infertility • Absence of Implantation

- In some women, the preembryo may reach the uterus but implantation does not occur • Priming of the uterus by estrogen and progesterone is needed for implantation to occur, and this priming may be inadequate in some women • Some of these cases can be treated by the administration of steroid hormones (estrogens or progestins) to render the uterine endometrium more receptive to the blastocyst - Other cases of infertility may be due to damage to the endometrium • Perhaps fibroids or scars from pelvic infection are present or a previous unsafe abortion may have damaged the uterine lining

Environmental Pollutants

- Many environmental pollutants can be teratogenic or mutagenic - Most of these agents have the most damaging effects during the 4th to the 7th weeks of pregnancy (Fig.10.13) • Before this time, they can kill the embryo; after this time, they have less chance of harming the fetus • Examples of mutagens are mercury, lead, cadmium, arsenic, PCBs, DDT, benzene, and carbon tetrachloride • In Japan, between 1932 to 1968 mercury from fertilizers in factory effluent got into the fish population and caused Minimata disease, first identified in 1956, which is characterized by damage to the fetal brain, resulting in abnormal muscle movement • Cerebral palsy (spastic muscle paralysis due to brain damage) is another name for this type of damage, which can be caused by fetal exposure to bacterial infection, oxygen deficiency, anemia, jaundice, and low blood

Bacterial STDs • Syphilis

- Syphilis is a serious STD caused by a bacterium, Treponema pallidum • About 5.5 million people in the world are diagnosed with syphilis each year (Fig. 17.2). • In the US, its incidence has been decreasing since reporting began in 1941, with the exception of a sharp, transient rise around 1990 • The number of new cases in the US reached an all-time low in 2000 • Control of the disease has been especially successful among African Americans and people living in the South, where syphilis has been historically prevalent • Opportunity now exists to eliminate the disease in the US • Currently, about 46,000 new cases are reported each year • As with gonorrhea, the actual incidence is higher because many cases are not reported (Fig. 17.1) - Transmission • Treponema pallidum is a corkscrew -shaped (spirochete) bacterium • It thrives in moist regions of the body and will survive and reproduce only where there is little oxygen present • It is killed by heat, drying, and sunlight • Therefore, one cannot catch syphilis from contact with toilet seats, bath towels, or bedding • It can, however, live in collected blood for up to 24 h at 4°C and thus, in rare cases, is transmitted during blood transfusion • Nine out of 10 cases of syphilis transmission occur during sexual intercourse, although it can also be introduced into an open wound in the skin • Fortunately, only about one in 10 people exposed to the bacterium develops syphilis • People infected with syphilis can acquire the HIV virus more easily and transmit it to others - Stages of the disease - Primary Stage • The symptoms of untreated syphilis occur in four stages - The primary stage of syphilis usually appears as a single sore called a chancre (pronounced shang'ker) at the place where the bacteria first entered the body - This is a round, ulcer- like sore with a hard raised edge and a soft center - It looks like a crater, approximately 0.5- 1 in in diameter - This chancre, which for all its awful appearance is painless, appears 10-90 days after entry of the bacteria - Because the chancre is painless and may be in a location not readily noticed, a person may not realize that he or she is infected - In males, the chancre usually occurs on the glans or corona of the penis, but it can occur anywhere on the penis or on the scrotum - In females, it usually appears on the vulva, but sometimes can occur on the cervix or vaginal wall - After oral coitus with an infected person, it can appear on the lips, tongue, or tonsils, and it can appear in the anus after anal - Lymph nodes enlarge a few days after the sore appears-the chancre heals in 1-5 weeks, and the primary stage is then over - Bacteria travel in the blood or lymphatic system to other parts of the body and, in one -third of cases, they will eventually cause the secondary stage - Secondary Stage • The secondary stage of syphilis occurs 2 weeks to 6 months after the primary stage - Characterized by a rash that appears on the upper body, arms, hands, and feet and can spread to other skin regions. In light-skinned people, the rash appears as cherry - colored blemishes or bumps that change to a coppery-brown color - In dark-skinned people, the blemishes are grayish blue - Larger bumps can develop and burst - The rash does not itch and is painless, but the syphilis bacteria are present in great numbers in these sores, and contact with the sores is very infectious to other people - Other symptoms of the secondary stage can include hair loss, sore throat, head-ache, loss of appetite, nausea, constipation, pain in the joints and abdominal muscles, a low fever, and swollen lymph glands - The symptoms are minor and cause little inconvenience in about 60% of untreated individuals in the secondary stage; thus, they may be completely overlooked - The secondary stage goes away in 2-6 weeks but can recur over the next 1-2 years, after which the untreated individual then enters the latent stage of syphilis - Latent Stage • During the latent stage of syphilis, which can last for years, a person exhibits few or no symptoms • An individual in the latent stage can no longer transmit the bacteria (except to a fetus) • About half of the people who enter the latent stage never leave it, even if not treated • The other half eventually enter the tertiary stage of syphilis if not previously treated with antibiotics - Tertiary Stage • Entrance into the tertiary stage of syphilis occurs because the bacteria have invaded tissues throughout the body, although people in the tertiary stage are not infectious • The tertiary stage is characterized by large, tumor-like sores (gummas) that form on tissues of skin, muscle, the digestive tract, liver, lungs, eyes, nervous system, heart, or endocrine glands • Infection of the heart (cardiovascular syphilis) can cause severe damage to the heart and its valves • Invasion of the bacteria into the central nervous system causes neurosyphilis, and the brain and spinal cord can be severely damaged • People with neurosyphilis can develop partial or total paralysis, blindness, or psychotic and unpredictable behavior • Damage from tertiary syphilis can cause death - Congenital Syphilis • A person is not infectious in the latent or tertiary stages of syphilis - This is true except in the case of an infected pregnant woman, who can pass the bacteria to her fetus at any stage of syphilis - The placenta protects the fetus against invasion of syphilis bacteria up to about the sixth month of pregnancy, after which time the T. pallidum bacteria can pass through the placental membranes into the fetal bloodstream - Then the fetus can contract the disease from the mother - If this happens, about 30% of the fetuses miscarry and 70% are born with congenital syphilis - The latter children are contagious in their first and second year and go through all the stages of syphilis if left untreated - About 23 in 100 such cases develop tertiary syphilis in 10-20 years - Symptoms of tertiary congenital syphilis include damage to the eyes, deafness, flattening of the bridge of the nose (―saddle nose‖), and central incisor teeth that are spread apart and notched (―Hutchinson's teeth ‖) - Many of these individuals die from this affliction - Because of the serious consequences to the fetus and newborn, every pregnant woman should be tested for syphilis - Diagnosis • Several of the symptoms of syphilis can be confused with those of other STDs • Also, it has proven difficult to grow cultures of T. pallidum in the laboratory • Therefore, other tests are necessary to see if a person has contracted the disease • Diagnosis of syphilis can be accomplished by combining the results from two blood tests - A nontreponemal blood test looks for signs of infection but does not pinpoint the cause - A positive result is followed by a treponemal blood test, which detects antibodies that are specific to T. pallidum - False-positive results occur in one out of 3000 of these blood tests and, more importantly, false negatives occur - Because of this error factor, an individual's tissues should also be checked for the presence of live T. pallidum, based on their characteristic shape and movement, using a dark-field microscope to confirm the diagnosis - Treatment • Once it has been determined that a person has syphilis, treatment with one of several antibiotics is effective • Most commonly, benzathine penicillin G is given as a single injection each day for 8 days if the person is in the primary stage and for 3-4 weeks at higher dosage if the person is in a more advanced stage of the disease • Tetracycline or erythromycin can be used if a person is hypersensitive to penicillin • It must be emphasized that syphilis, like gonorrhea, is a curable disease • Individuals with tertiary syphilis, even if treated, still may suffer permanent tissue damage

STD introduction

- The incidence rate (number of new infections per year) of these approximately 25 diseases is very high • Nearly 20 million Americans will contract an STD each year- considerably higher than in most other industrialized nations • Young people are disproportionately affected: Half of STDs occur in young people aged 15-24 years, despite this age group accounting for only 25% of the sexually active population • For some STDs there is no cure, so individuals can remain infected for the rest of their lives • The prevalence rate (new and existing cases) of STDs is greater than the number of new cases of these infections; STD prevalence is estimated to be more than 110 million infections among men and women in the US • Organisms causing STDs usually do not live and reproduce on dry skin surfaces - They require the moist environments of membranes in the so-called transitional zones of the body —those that occur at openings between the external and the internal body surfaces • These transitional zones include the vulva, vagina, and urethra of the female; the penis and urethra of the male; and the mouth, oral cavity, eyes, and anus of both sexes • These zones usually are where the STDs first gain a foothold; from there, they can invade other body tissues - Sexual reproduction requires direct genital contact • This provides an ideal transmission route for bacteria, viruses, and other infectious agents • Some STDs can also be passed from an infected pregnant woman to her fetus or between individuals through contact with body fluids, such as infected blood - Although the body forms antibodies to some of the STD microorganisms, for may infections immunities are slow to develop or may never occur • a person frequently has more than one STD at the same time • in fact, the sores or lesions produced by one STD can increase the risk of infection by another STD • the present yearly occurence of several STDs in the US and worldwide are summarized in 17.1 and 17.2 • the CDC requires health workers to report conifrmed cases of six sexually transmitted infections: chlamydia, gonorrhea, syphilis, chancroid, hepatitis B, and HIV • for most of these diseases, many more cases occur than are reported - There are many reasons that an STD may not be diagnosed • First, many people with these infections are asymptomatic or have only mild symptoms, so they may have a disease and spread it to others without knowing that they have an STD • Secondly, the symptoms of many STDs are similar to each other and to infections of the vagina and urethra that are not sexually transmitted • Many STD infections occur among young people, who may not have ready access to health care or who may not recognize the symptoms • Finally, a general societal reluctance to openly discuss sexuality and sexual health issues may limit people from seeking medical diagnosis and treatment of STDs

assisted Reproductive Techniques (ARTs) • Gamete Storage and Artificial Insemination

- When sperm are introduced into a woman's reproductive tract by means other than coitus, it is called artificial insemination (AI) • The sperm can come from a "donor" man who is not the woman's husband or partner (artificial insemination donor, AID) or from the husband (artificial insemination husband, AIH) • In both cases, the man deposits semen into a vial by masturbating or into a specially designed condom during intercourse • Several ejaculations, which are collected and frozen, are usually required to pool enough sperm to be effective • If a man's sperm count is very low, sperm can be retrieved directly from the testes by testicular biopsy • A sperm sample can also be taken from the epididymis using a tiny syringe or by aspirating epididymal fluid using microsurgery - If the quantity of motile sperm is sufficient, the pooled sperm sample is "washed" (processed to concentrate motile sperm in a small amount of fluid) and then loaded into a thin, flexible catheter and delivered into the woman's uterus - This usually involves only slight discomfort - The timing is critical; sperm should be introduced into the uterus within a few hours of ovulation (intrauterine insemination, IUI) - Fertility drugs can be used to induce ovulation of several oocytes, thus improving the chances for fertilization - If the male partner cannot produce sperm of sufficient quantity or quality or if a single woman wishes to become pregnant without a partner, donor sperm from a "sperm bank" can be used • Donors are classified, anonymously, by their physical and even personality characteristics, and some sperm banks screen semen for hereditary diseases and chromosomal abnormalities • Transmission of the human immunodeficiency virus (HIV) from the use of donor artificial insemination is possible, and for this reason sperm banks are required to test semen samples for the presence of HIV antibodies • Sperm can be frozen at −196°C (−321°F) for up to 10 years • Artificial insemination can be useful for couples with certain causes of infertility, such as when the male partner has a low sperm count or if the female has cervical irregularities that prevent movement of the sperm into the uterus - Sperm storage can also be useful for a man who is going to have a vasectomy, just in case he may later want to father a child • Artificial insemination is a less costly fertility treatment than methods that rely on egg retrieval • However, the success rate of AI averages only 10-20% per cycle, and some couples must repeat the procedure multiple times to achieve pregnancy • It is less successful in couples with a lengthy period of infertility, when the female partner is older or has a history of pelvic inflammatory disease or endometriosis, or when the male partner has very low sperm count or a high percentage of abnormal sperm

identify the most false statement

estrogens control the development of the reproductive organs in the female fetus

Pregnancy Loss (Miscarriage)

• About 10% of known pregnancies end in miscarriage - However, these losses represent only a small portion of pregnancy losses • It is estimated that 50 -70% of all fertilized eggs do not complete development • Several studies of healthy young married women from a variety of study populations followed their attempts to conceive • Researchers were able to detect early pregnancy losses using sensitive assays of hCG • The studies found that 20-30% of pregnancies are lost after implantation but before the expected time of the next menstrual flow (around days 8-14 postfertilization) • Prior to implantation (about days 1-7 after fertilization), loss of the conceptus is difficult to detect • However, it is certain that some preembryos do not successfully implant, and estimates of preimplantation loss are as high as 30% - Very early pregnancy losses are sometimes called "occult" because they occur before a woman realizes that she is pregnant • Miscarriage is the most common disorder of pregnancy • Unfortunately, some women are infertile because they experience recurrent miscarriages (usually defined as three or more miscarriages) • Most early miscarriages occur because of chromosomal abnormalities of the fetus, usually because of errors introduced during meiotic disjunction in the oocyte or sperm • A woman who has had repeated miscarriages may simply have the misfortune to have carried fetuses with unrelated chromosomal anomalies • Women over age 35 have an increased risk of miscarriage, probably because mutations accumulate as the egg ages or the oocyte's meiotic apparatus becomes less accurate • Some miscarriages do not have an apparent genetic cause • Possible immunological causes of miscarriage - It was suspected that couples who shared certain major histocompatibility complex (MHC) antigens were at higher risk for miscarriage, but there is no clear evidence to support this idea - Current research is focused on one MHC gene (human leukocyte antigen [HLA]- G) that is expressed mostly in fetal tissues of the placenta, the cytotrophoblast - Because it is found where maternal and fetal cells interact, this antigen may play a role in the support of pregnancy - The presence of certain HLA-G variants in the man and/or woman can increase a couple's risk of having a miscarriage

Bacterial STDs

• Bacterial genetic material is a single, circular molecule of DNA not arranged into a chromosome - Many bacteria cause disease by producing toxins - Bacterial infections that cause STDs can be cured by antibiotics - Concern is rising that some strains of bacteria that cause STDs, especially gonorrhea, are developing resistance to commonly used antibiotic drugs - It is recommended that all sex partners of an infected person also be treated with antibiotics - Individuals should abstain from sexual contact until all medicine has been taken and the symptoms disappear - Treatment cures the present infection, but it is certainly possible to become reinfected with a bacterial STD after recovery from a previous infection

ssisted Reproductive Techniques (ARTs) • In Vitro Fertilization (IVF) - Fertilization and Embryo Transfer

• Before the ova are retrieved fresh sperm from the male partner/donor are placed in a petri dish • The dish contains a fluid that nourishes and capacitates the sperm • The ova are then added to the dish with the sperm, and fertilization, as evidenced by the presence of two pronuclei, usually occurs within 12-14h • Here it is possible to use a donor ovum instead of the ART patient's own ovum, donor sperm, or even a donor ovum and donor sperm • After fertilization, the embryos are transferred to a new culture dish for incubation, and their development is monitored closely • It takes 2 days for an embryo to reach the two-to four-cell stage; in 3 days, the embryo has about 32 cells • By the fifth day, the embryo has become a blastocyst • Embryos that exhibit normal development are transferred into the uterus usually between 3 and 5 days after fertilization • The preembryos are placed into a tiny tube, which is inserted into the woman's uterus through her cervix • Finally, the embryos are released into the uterus, and implantation can now occur • It takes about 2 weeks to know if one or more embryos have implanted • Most ART clinics transfer only two or three embryos in one in vitro fertilization cycle • The remaining eggs or embryos can be frozen for possible use in future IVF cycles • In intracytoplasmic sperm injection (ICSI) technique, a single sperm is injected directly through the zona pellucida and into the ovum - Currently, 75% of the ART cycles in the United States use ICSI • Another method is assisted hatching or zona drilling, in which part of the zona pellucida is removed from the preembryo's surface - This may facilitate hatching of the preembryo prior to implantation • In an effort to rejuvenate aging eggs, cytoplasm from a young donor egg is injected into the egg of an older ART patient, a process called cytoplasmic transfer - This highly experimental treatment has had some limited success, which may be explained by the introduction of healthy mitochondria into the oxidatively weakened eggs - Embryos resulting from this treatment, however, would have mitochondria from two different females instead of inheriting mitochondria from the mother only, as in normal development - The long-term consequences of this are unknown

Infertility introduction

• CDC: ~ Six million (one in 10) women in the US are infertile- other estimates put the number at 15% - A couple is considered infertile if they have participated in unprotected coitus for a year without becoming pregnant • Infertility in men and women- approximately 35% each • Infertility in both partners- approximately 20% • In 10% of cases, the cause is unknown - A couple can also be infertile because of pregnancy wastage, or the inability to maintain a pregnancy once established - Cause of infertility can be diagnosed in 85- 95% cases • Can be successfully treated in 50-60% cases

Assisted Reproductive Techniques (ARTs) • In Vitro Fertilization (IVF) - Ovarian Stimulation and Egg Retrieval

• Fertility drugs (usually FSH analogs) are administered to cause several large follicles to mature in a woman's ovary • GnRH agonists or antagonists may be used additionally to prevent premature ovulation • Growth of the follicles over the next 8- 14 days is monitored using ultrasound • Circulating hormone levels are also checked - During follicular growth, estrogen levels should rise but progesterone levels should remain low - When several large follicles have grown, an injection of hCG is usually given - This mimics LH and causes the eggs to mature and also triggers ovulation • Before ovulation occurs, oocytes (ova) are removed from the large follicles in the ovary • In most cases, several (up to 12) ova are removed to ensure a sufficient number of embryos to transplant • The operation involves inserting a long needle through the vaginal wall toward the surface of the ovary • Guided by ultrasound, the needle contacts each enlarged follicle and the ovum is removed by suction • It is also possible to monitor and retrieve oocytes that develop naturally without the use of fertility drugs, but this method is infrequently used

ssisted Reproductive Techniques (ARTs) • In Vitro Fertilization (IVF) - Gamete or Zygote Intra - fallopian Transfer (GIFT or ZIFT)

• Gamete intrafallopian transfer (GIFT) is used for infertile women who are ovulating but have blocked oviducts (fallopian tubes) or for infertile couples who, for religious reasons, wish to avoid fertilization outside the human body - Mature ova are removed from large follicles in the infertile woman's ovary, as in the IVF method - Then the ova are inserted by laparoscopy into one of the woman's oviducts below the point of blockage, and the sperm sample is also placed into the oviduct with the ova - Fertilization and implantation then can occur; steroid hormones (estradiol, progesterone) may be administered to assist implantation and prevent miscarriage • In a variation of this method, ova are removed and fertilized with the male partner's sperm in vitro • Then, zygotes (single diploid cells) are inserted into the oviduct and allowed to travel down the oviduct before implantation • This is called zygote intra- fallopian transfer (ZIFT) - Success rates for ZIFT and GIFT are about the same as for IVF

Female Infertility • Some infertile women have high prolactin levels in their blood - The drug bromocriptine, which inhibits prolactin secretion, restores fertility in many of these women

• In some infertile women there may be no problem in the hypothalamus and pituitary, but ovaries may be unresponsive to the gonadotropins - Due to the presence of endometriosis, ovarian cysts, tumors, or scars caused by ovarian infection • In these cases, ovarian surgery may be needed to restore fertility • Some women have permanently malfunctioning ovaries - The ovaries of women with Turner syndrome (XO), for example, lack follicles • Between 5% and 10% of adult women have symptoms of polycystic ovarian syndrome (PCOS); these symptoms include excess androgen secretion, menstrual disorders, a tendency toward obesity and insulin resistance, and anovulation • Although not all women with PCOS have difficulty in becoming pregnant, this syndrome is a leading cause of subfertility or infertility in women - For some overweight women with PCOS, weight loss alone can restore fertility • Clomiphene or other fertility treatments are also commonly prescribed - Ovulation may be suppressed in women who have extremely low body weight, who are obese, or who exercise excessively - Fertility can also be impaired in women who take excessive amounts of alcohol, nicotine, or illicit drugs • In some cases, lifestyle changes to address these issues can restore fertility

• The Fetal Period - Circulatory System

• In the adult, deoxygenated blood (poor in oxygen and rich in carbon dioxide) enters the right side of the heart and then is pumped to the lungs via the pulmonary trunk and arteries • In the lungs, carbon dioxide is removed and oxygen is picked up • The oxygenated blood then returns to the left side of the heart via the pulmonary veins and is pumped to the dorsal aorta, which carries arterial blood to all other tissues • The placenta, not the lungs, is the respiratory organ of the fetus, so the fetal circulatory system is different from that of the adult (Fig.10.12) • After the oxygenated blood enters the right side of the fetal heart and is pumped into the pulmonary trunk, it is prevented from going to the collapsed lungs by a blood vessel shunt that goes from the pulmonary trunk to the dorsal aorta, the ductus arteriosus • The deoxygenated blood then reaches the placenta via the umbilical arteries, where it loses carbon dioxide and picks up oxygen • The oxygenated blood then travels via the umbilical vein back to the fetus, eventually reaching the right side of the fetal heart • Another shunt, the ductus venosus, shunts blood around the fetal liver (Fig.10.12) • The ductus arteriosus and ductus venosus close after birth • The volume of blood flowing through the left and right side of the heart should be equal or the pumping action would become inefficient • In the fetus, no blood flows from the lungs into the left side of the heart as in the adult • A hole (covered by a flap) in the wall separating the left and right atria of the fetal heart, allows blood to mix between the sides and to balance the heart • This hole, the foramen ovale (Fig.10.12), closes after birth

Injectable Hormones

• Injectable progestin (Depo-Provera, or "the shot") is another method that delivers progestin directly into the body tissues - The progestin medroxyprogesterone acetate is injected into the muscle of the leg, arm or buttock once every 90 days and works by decreasing GnRH pulsatility, which inhibits the LH surge, thus preventing ovulation • It also causes thickening of the cervical mucus, inhibiting the movement of sperm through the cervix • A subcutaneous shot containing a slightly lower dose of the progestin has also been developed • Injectable progestin is a very effective contraceptive method • Failure of these injections is only about 0.3% when repeat injections are received regularly every three months, and women need not remember to take a daily pill - Women who cannot take estrogen or who are breast-feeding can use progestin-only injectable birth control • The disadvantages and side effects of Depo- Provera are similar to those of the subdermal progestin implant • Injectable progestin also has been shown to cause bone loss; this should be taken into consideration especially for use among adolescent girls, who are building up bone density, and for women at risk for osteoporosis • If a woman stops this method, she will usually be fertile 3- 18 months after the last injection • This delay in return to fertility compared with other hormonal contraceptive methods may be related to the relatively high levels of hormone that are released slowly and that may take several months to clear from the body

Fetal Disorders

• It is estimated that about 30% of preembryos die prior to implantation - Another 30% are lost after implantation but before the next menstrual period is expected - An additional 10% of embryos die after the missed menstrual period - Altogether, only about one- third of human fertilized eggs complete development and result in live births - Usually the conceptus is lost before a woman recognizes that she is pregnant - Of confirmed pregnancies, 15-20% end in spontaneous abortion (miscarriage) - Most of these embryos or fetuses have chromosomal abnormalities - Fortunately, the vast majority of fetuses that survive through pregnancy are born as healthy infants • About 2% of newborns have serious birth defects (major congenital disorders) • These may be caused by genetic mistakes or prenatal exposure to harmful substances - Genetic and Chromosomal Disorders • The fetus can inherit genetic disorders • About 4000 human diseases are of genetic origin • Some of these disorders are mild, such as colorblindness • Others can cause major handicaps such as harelip, cleft palate, and club foot • Many others can kill the embryo or fetus • Chromosomal abnormalities account for about 50% of spontaneously aborted fetuses and are present in one out of 200 newborns

Induced Labor

• Labor can be induced before term, near term, or after the due date by administering synthetic oxytocin and/or prostaglandins - First, the physician often will break the amniotic membrane because this alone may begin labor and hormones may not need to be administered - Oxytocin is given intravenously - Prostaglandins also can be given intravenously or be injected into the amniotic sac, given orally, or administered as a vaginal suppository - Oxytocin can be released naturally from a woman's pituitary by stimulating the nipples manually or with a breast-feeding pump • This method may be used alone or to augment other methods • One reason for inducing labor is if the birth is two weeks overdue - Many "late" pregnancies are in fact miscalculations of the due date, and there may therefore be a danger of delivering a premature baby if labor is induced in such cases - The physician usually can determine fetal maturity by physical and physiological characteristics - About 8-12% of babies are born postmaturely in the US - Early labor can be induced artificially before 36 weeks of pregnancy - This can be done, for example, if the amniotic sac has burst 12-24 h beforehand and labor has not yet begun • A broken amniotic sac increases the danger of neonatal and maternal infection

Hormonal Contraception

• Ovulation does not normally occur during the luteal phase of the female cycle nor when a woman is pregnant - During these times, high levels of progesterone (as well as moderate levels of estrogens) exert negative feedback on the hypothalamus and pituitary • The hypothalamus responds by producing less GnRH , and this causes the pituitary to release lower amounts of gonadotropins • Follicular growth slows down because of a reduction in FSH, and suppression of LH inhibits ovulation • Exogenous administration of progesterone or other progestins can mimic this effect, overriding the body's natural hormonal cycle and preventing ovulation of a mature ovum • Thus , maintaining a luteal phase - like progestin level is an effective method of contraception 9 Hormonal Contraception - Progestins can be injected, taken in the form of a daily pill, or applied as a patch, ring, or other device from which they are absorbed across the surface of the skin or the reproductive tract • These hormones are typically given for three weeks, followed by a week's break from the hormones during which time the endometrium sloughs off and a "withdrawal bleeding" occurs - A woman experiences this as a menstrual flow • Although for some women the flow induced by withdrawal of hormones is lighter than a true menstrual flow because the endometrial build - up is less extensive - Estrogens may be given along with progestins, as estrogens also feed back on the hypothalamus and pituitary to inhibit gonadotropin release • The addition of estrogens to a progestin contraceptive also helps to reduce breakthrough bleeding (spotting or bleeding at times other than the scheduled withdrawal bleeding) by maintaining the endometrial layer of the uterus

Maternal Complications of Pregnancy

• Preeclampsia - Also called toxemia is a condition that develops in the last one or two months of pregnancy in 6- 7% of all pregnancies in the US - It is the leading cause of maternal and fetal death - More common in primiparous women and in multiparous women over 35 years of age than in other females - Other risk factors are preexisting obesity or high blood pressure, a pregnancy with twins or more, and having a close relative who has experienced toxemia - The symptoms of preeclampsia are high blood pressure (hypertension), fluid accumulation in tissues (edema), and an increased excretion of proteins in the urine (proteinuria) - If this condition is not controlled by diet, a more severe form (eclampsia) can develop, characterized by convulsions, coma, and death in about 15% of cases - No animal models, no cure for severe cases • Gestational Diabetes - About one out of 350 pregnant women in the US develops gestational diabetes mellitus due insulin resistance - Insulin is a hormone that promotes the entry of glucose into cells where it is used as energy - Mild insulin resistance is normal in pregnancy, as human placental lactogen and other pregnancy hormones decrease maternal sensitivity to insulin, thus increasing blood glucose available for fetal growth - The pregnant woman compensates by increasing her pancreatic insulin production - If blood glucose levels are not held in check, however, gestational diabetes occurs - As a result, copious amounts of urine, containing glucose, are produced • This is not only damaging to the mother if not controlled, but also puts the fetus at risk • The fetus tends to grow abnormally large (macrosomia) in response to the increased availability of nutrients • Synthesis of fetal insulin rises in response to high glucose levels • At birth, the fetus is suddenly deprived of its former high glucose nutrient source, and the elevated insulin in its body causes it to become hypoglycemic, sometimes causing seizures, coma, and brain damage • Gestational diabetes can often be controlled by diet and moderate exercise, but medication to control blood sugar may be necessary, and pregnant women with this condition should be monitored carefully

Physiological Changes during Pregnancy

• Pregnancy makes great demands on the body - maternal adaptations to pregnancy are found in all organ systems - Increased cardiovascular function is needed to supply blood to the highly vascular placenta - Blood volume increases 45-50% - Because the increase in number of red blood cells (20-30%) is not as great as the increase in blood volume, a pregnant woman's hematocrit falls - This means that her blood is thinner, perhaps facilitating perfusion of the placenta - A woman's heart rate also increases during pregnancy causing an increase in cardiac output (volume of blood per unit of time), which is needed to push blood into the placenta - The respiratory rate also increases by about 40% - This hyperventilation increases the ratio of O2 to CO2 in the pregnant woman's blood, facilitating the transfer of O2 to the fetus and the removal of CO2 from fetal to maternal blood - To filter this extra volume of blood, the kidneys enlarge and increase their filtration rate by 50%

Time of Birth

• The average length of pregnancy in humans is about 9 calendar months - The due date (or term) can be calculated by counting 280 days (40 weeks) from the first day of the last menstruation - The due date can also be determined by counting 266 days (38 weeks) from conception - Usually, ovulation and fertilization occur 13-15 days after the first day of the last menstruation, but conception can also take place at other times after day 1 of the cycle • The duration of pregnancy is affected by many factors - Multiparous women (those who have previously given birth) usually have shorter pregnancies than those giving birth to their first infant (primiparous) - Women carrying multiple pregnancies (twins or more) generally have shorter gestations than those with singleton pregnancies - Gestation length can also be affected by socioeconomic factors, psychological stress, maternal age, and health issues such as weight, previous history of preterm delivery, and preexisting conditions such as diabetes - Birth within 2 weeks before or after the due date is considered normal - Seasonal birth cycles occur in virtually all human populations, regardless of race, but interestingly the patterns of seasonality differ in various regions • In North America, the lowest number of births is in the spring, and there is a seasonal peak in the fall (Fig. 11.1) • The magnitude of the seasonal change is greater in the southern (lower latitude) regions and lower at more northern latitudes • This North American pattern is also true for the Mideast, Asia, and Africa • Europe differs in that a seasonal birth peak occurs in the spring and a low in the winter (Fig. 11.2) • The magnitude of the seasonal change in Europe is greater the higher the latitude - In the North American pattern, the seasonal high in fall births corresponds to higher conception rates in winter, whereas the spring low in births corresponds to lower conception rates in the hottest months of the year • Because there is a lowering of sperm count and blood testosterone levels in American men around this same time, the decrease in spring and early summer conceptions could be caused by an adverse effect of high temperature on sperm count or coital frequency • In Europe it is thought that day length plays a greater role in causing the spring pattern of births - Whatever the causes, the seasonality in human births and conceptions may be evolutionary remnants of more pronounced seasonal cycles such as those that occur in wild primates as adaptations to seasonal food supplies • There is also a daily cycle in the frequency of human birth • More babies are born at night than during the day, with a small birth peak between 4:00 and 9:00 am • May be an evolutionary vestige - perhaps as a protection against predators active during the day

The Birth Process

• The birth process can be divided into three stages • Cervical effacement and dilation • Expulsion of the fetus • Expulsion of the placenta - The length of each stage varies among individuals and in the same individual between first and subsequent births - The entire process of labor and birth typically lasts from 8 to 14 h in women giving birth for the first time (primiparous women) but is shorter (4-9h) in women who have previously had a child (multiparous women) - Any length of labor up to 24 h, however, is considered normal • Eventually, true labor commences; the uterine contractions become more intense and they occur at regular intervals - These effacement contractions usually are felt in the back and then in the abdominal wall (or vice versa); they reach a peak and then relax • Early effacement contractions are usually mild but become progressively stronger, more long lasting, and more frequent • The contractions can be felt and timed by placing a hand on the upper abdomen • Each contraction lasts about 30-60s, with intervals between contractions of about 5 -20min (Fig.11.5) • The result of effacement contractions is cervical effacement, which means a thinning of the normally thick walls of the cervix and retraction of the cervical tissue upward into the uterus, making it easier for the fetus to pass into the birth canal - During pregnancy the cervix is blocked by a mucous plug • At, or immediately before the beginning of effacement contractions, mucus is dislodged along with a small amount of blood, and this bloody show (pinkish in color) exits through the vagina • At this time, or in the first stage, an enzyme weakens the amnion • A small tear then appears in the amniotic sac (made up of chorion on the outside and amnion on the inside), and clear amniotic fluid trickles or gushes from the sac and is expelled through the vagina • This bursting of the amniotic sac (breaking of the bag of waters) and the bloody show are sure signs that true labor is commencing • In about 12% of pregnancies, the amniotic sac breaks before labor begins • These "dry labors" proceed normally but often are shorter than usual • It is also common for the sac to remain intact after labor has advanced considerably - Physician or midwife will puncture the amnion with an instrument (this does not hurt the mother, as there are no pain receptors in the amnion)

How the Combination Pill Works

• The combination pill prevents conception by inhibiting ovulation - Hormones in the pill mimic the negative feedback effects of estrogens and progesterone present during the luteal phase of the menstrual cycle and in pregnancy • They limit GnRH secretion and the release of pituitary FSH and LH • By reducing the levels of FSH in the blood, the combination of estrogen and progestin in the pill inhibits tertiary ovarian follicle growth • Because large preovulatory follicles fail to grow, no estrogen surge occurs at mid cycle • This prevents the surge of LH secretion from the pituitary that normally causes ovulation during the middle of the menstrual cycle • The combination pill also renders the cervical mucus hostile to sperm transport, so even if the pill fails to prevent ovulation, conception does not occur - Hormones in the pill also cause the uterine endometrium to be unreceptive to the embryo because the E:P ratio, although effective in blocking ovulation, is not quite sufficient to support implantation

• The Fetal Period - Endocrine System

• The endocrine system of the fetus is functional during most of pregnancy • The fetal anterior pituitary gland secretes the gonadotropins FSH and LH, and these hormones may influence the development of the fetal gonads • Some hCG also reaches the fetus and may be involved in fetal gonadal function • The fetal pancreas secretes insulin, which allows fetal cells to use glucose supplied by the mother • The fetal adrenal glands contain a special region that secretes steroid hormones that may play a role in the initiation of labor (Chapter 11) • The fetus is surrounded by amniotic fluid, and there is a constant turnover of this fluid throughout pregnancy • Two hormones are involved in the regulation of amniotic fluid secretion and absorption 1) Prolactin secreted by the placenta, which is found in high levels in amniotic fluid and is known to play a role in pumping sodium and therefore water across membranes 2) Arginine vasotocin (AVT) secreted by the fetal neurohypophysis • The adult neurohypophysis secretes oxytocin and vasopressin, not AVT • In some aquatic animals, AVT is an adult hormone that is involved in water transport across membranes • Because AVT secreted by the fetus is involved in the regulation of its amniotic "pond," fetal AVT secretion may recapitulate the role of this hormone in our aquatic vertebrate ancestors

• The Fetal Period - Digestive/Urinary Systems

• The fetus derives nutrients from the mother's blood in the form of glucose, amino acids, fatty acids, vitamins, salts, and minerals • Nutrients pass to the fetus in the umbilical vein and are utilized by fetal tissues • Carbon dioxide and other wastes of fetal metabolism pass back to the placenta via the umbilical arteries- excreted by the mother • In late pregnancy, the fetus swallows about 500ml of amniotic fluid each day, and this fluid contains water, salts, glucose, urea, and cell debris from the amnion and fetal skin • These ingested materials provide some nourishment for the fetus, and the waste products from this digestion combine with bile pigments to form feces in the large intestines - This fecal material, called meconium, is the first to be defecated by the neonate • The fetal kidneys are functional throughout pregnancy and toward the end of prenatal development produce about 450 ml of urine per day, which is excreted into the amniotic fluid

Labor and birth introduction

• The internal relationship between mother and fetus terminates in childbirth, or parturition - Timing of birth and the role of hormones in the birth process - Hormonal control of birth has allowed induced labor - Stages of labor and birth and some aspects of premature, multiple, and difficult births - Use of medications during labor and birth and birthing methods

• The Fetal Period - Nervous System

• The nervous system of the fetus is formed very early in development • The CNS (brain and spinal cord) and peripheral nerves develop by the 8th week and influence development and function of skeletal muscles so neuromuscular control appears at an early stage • After the fetus begins to move on its own, some of its movements are well coordinated • The fetal sensory nervous system also is functional, and the environment in the uterus is not totally devoid of stimuli • For example, the noise level within the amniotic sac is similar to that of a quiet room (about 50dB), and the light is like a dark room • The temperature of the amniotic fluid is about 0.5°C higher than the mother's body temperature because the rapidly growing fetal tissues produce heat • It has been shown that a loud noise outside but near the woman's abdomen, a flash of light within the amniotic fluid, or pricking the fetal skin with a small instrument can evoke vigorous fetal reactions • The fetus, even in early stages, is not simply an inert, growing lump of tissue, but a moving, sensing organism that is capable of responding to changes in its environment

Sperm Passage through the Cumulus Oophorus

• The ovulated ovum is surrounded by the cumulus oophorus, which is a sphere of loosely packed follicle cells (Fig. 9.4) - Cumulus oophorus means "egg- bearing little cloud" - The enzyme hyaluronidase on the sperm head dissolves hyaluronic acid, a major component of the cementing material found between the cells of the cumulus oophorus as well as between other cells in the body - Enzymatic dissolution of hyaluronic acid allows the swimming sperm to penetrate the spaces between cells of the cumulus oophorus and to reach the zona pellucida

Use of the Combination

• The pills usually come in 21- or 28- day cycle packages • One pill each day, usually beginning on the Sunday after the last menses began • Continue for 21 days- ovulation is suppressed • Then either stop taking any pills for seven days or switch to an inert "reminder" pill for the remaining seven days of the cycle • After stopping the hormonal pill, menstruation- like withdrawal bleeding begins • A woman is unlikely to get pregnant during the seven-day period when she is not taking the hormonal pills because she is menstruating for a few days and an embryo would not likely implant during the menstrual flow • Also, seven days is not long enough for follicular growth and ovulation to occur - If she misses one day of taking a hormonal pill, she can take two the next day with no loss of protection - If, however, she misses two or more days, she should stop taking the hormonal pills for seven days and then begin a new pill cycle-other methods - Other forms of combination pills are available • The one discussed earlier is called monophasic because all of the active, hormone- containing pills have the same dose of estrogen and progestin • Biphasic and triphasic pills were designed to more accurately mimic the changing hormonal levels in a natural cycle • Each package contains two 14-day or three seven-day sequences of pills with changing amounts of estrogen and/or progestin • They are as effective as the monophasic combination pill in preventing pregnancy • A 28-day series consisting of 24 active pills and four placebo pills is also available • Some newer formulations extend the period of active pills such that withdrawal bleeding occurs less often - In 2003 the FDA approved Seasonale, a 91-day pill sequence that delivers a fixed dose of estrogen and progestin for 84 days, followed by seven days of inactive pills during which time withdrawal bleeding occurs - A women taking the 91- day pill has a menstrual flow only once every three months - Lybrel, approved in 2007, contains a year's worth of combined oral pills - The failure rate of the combination pill is 0.3% for perfect use and 8% for typical use, with the higher figure present because some women forget to take, or are unable to take, a pill every day • This failure rate is very low in relation to rates of many other contraceptive devices • Contrary to popular belief, the use of common antibiotics (with the exception of rifampin) does not decrease the effectiveness of the combination pill • Certain other medications such barbiturates, antiseizure drugs, and the herb St. John's wort may decrease the effectiveness of combined oral contraceptives - Some women experience mild adverse side effects of the combination pill, usually during the first few months • Side effects can include nausea or (rarely) vomiting, bloating, fluid retention and slight weight gain, mood changes, headaches, breast tenderness, uterine bleeding between periods (spotting), changes in sex drive, increased blood sugar, minor blood clotting, increased blood pressure, and suppression of lactation if taken while nursing • Some women develop a persistent yeast infection in the vagina due to the increase in blood sugar levels • Some birth control pills are associated with a small increase in the risk of developing gall- stones - Not all women develop these symptoms, but a woman experiencing one or more of them may want to consult with her doctor about switching to a brand with a different dosage or a different kind of estrogen or progestin - The majority of women who stop taking the combination pill are fertile in three months or less, and pregnancy rates for the year after discontinuing use of the pill are comparable to those of non-pill users trying to conceive - There is no evidence that use of the combination pill impairs fertility

Hormones and Birth

• What factors determine when birth occurs? - Much of our current understanding about this question originally came from observations of the food habits of sheep - Pregnant ewes ate the plant Veratrum californicum, which delayed birth - Chemicals in this plant reduced ACTH secretion from the pituitary • Reduced cortisol • Reduced action on placenta to convert P to E • Estrogens cause uterine muscle contractions while progesterone blocks these contractions • Reduced E/P ratio causing delayed puberty • Hormonal Initiation of Human Birth - The fetal stress hormone system plays a similar role in human birth as in sheep, but with some important differences • In humans, it may not be the fetus that "decides" the time of birth, but the placenta, and the hormonal message is not cortisol but a rise in CRH • If an increase in CRH secretion plays a role in human birth initiation, the CRH likely is secreted by the placenta and not the fetus's or the mother's brain • Placental CRH activates the fetal pituitary and adrenal gland, causing increased adrenal secretion of androgens and cortisol • These hormones, respectively, result in increased estrogen levels in the mother and prepare the fetus for birth • Elevated cortisol levels further increase CRH production by the placenta, resulting in a positive feedback loop • The increase in placental CRH levels during pregnancy could be the "clock" that starts labor at the right time (Box11.1 & Fig. 11.3)

Sex preselection

• Couples who desire to choose the sex of their baby may now do so with some degree of success - A sperm- sorting technology (the microsort method) is the most effective procedure yet devised at separating X- bearing and Y- bearing sperm - It takes advantage of the fact that the large X chromosome has considerably more DNA than the tiny Y chromosome - A sperm sample is first collected from the prospective father - Then, the sperm cells are treated with a fluorescent dye that attaches to DNA and glows under laser light - Sperm with more DNA, scientists reasoned, would glow more brightly • Although X sperm have only 2.8% more DNA than those carrying a Y chromosome, the difference in brightness is sufficient to be distinguished by a light detector - The tagged sperm are sent through a very narrow tube with a diameter wide enough to allow only one sperm cell at a time - As sperm move through the tube, they are illuminated by a laser beam - An automated mechanical sperm sorter then separates the sperm, sending X sperm down one tube and Y sperm into another - The sorted sperm can then be placed in the woman's uterus (artificial insemination) or used for in vitro fertilization - Approximately 91% of sperm cells in the X-bearing tube contain an X chromosome - This procedure is only about 74% effective in selecting Y- bearing sperm - Thus, the results are not foolproof, but this method does improve the chances of producing an embryo of the desired sex, especially if a couple wishes to have a girl • Why would parents wish to preselect the sex of their offspring? - One reason would be to avoid sex- linked genetic diseases, which are more likely to occur in males - Parents may also wish to balance their families, or they may simply prefer to have a child of a given sex - Some have expressed concerns that the ability to select a baby's sex may be the first step to "designer children" chosen for other traits such as height, IQ, athletic, or musical ability - Others fear that widespread sex selection would lead to a gender imbalance in society and cause social problems • A preference for baby boys in China has led to a significant shift in the sex ratio in some areas of the country - In such cultures where boys are valued more highly than girls, the ability to select sex before fertilization could avoid costly and ethically controversial practices such as amniocentesis (genetic screening for sex) followed by selective abortion, or even infanticide - In the US, sperm selection likely would not lead to overall gender imbalance, as family preference for a female or a male baby is split more evenly - Finally, the ability to preselect a child's sex may help families limit their size - However, the present high cost of the microsort and PGD methods likely will limit the practice of sex preselection in the foreseeable future

Gamete Transport and Fertilization

• Fertilization involves fusion of the nucleus of a male gamete (sperm) and a female gamete - Restores the normal diploid (2N) chromosomal complement - Fertilization is preceded by and requires a series of precisely timed events - Sperm deposited in the female reproductive tract travel a relatively long distance and overcome several obstacles before reaching the ovum - The ovum also travels through a portion of the female reproductive tract before it is fertilized - The gametes also undergo important processes of physical and biochemical maturation that are a prerequisite for fertilization • Semen Release - After leaving the epididymides, sperm enter the vasa deferentia, which are long paired ducts serving as sperm storage and transport organs - Secretions of the male sex accessory glands (seminal plasma) mix with the sperm during ejaculation to form semen or seminal fluid - It has been theorized that the entire reserve of sperm in the epididymides and vasa deferentia would be depleted if an adult male had 2.4 ejaculations per day for 10 consecutive days - However, this normally does not occur because new sperm are produced continuously by the testes— about 200 million per day! - Thus, frequent ejaculation is not an effective method of contraception - Semen is released in three stages • Before male orgasm, a small amount of semen comes from the bulbourethral glands • Majority of the semen is released in the second stage- most of the seminal plasma of this stage comes from the seminal vesicles and prostate gland • In the third stage, another small amount of fluid produced by the seminal vesicles is exuded • Most of the sperm are expelled in the second stage, but some sperm are present in the semen of the first and third stages • Because sperm are present in the first stage, pregnancy can occur without male orgasm

Sperm Capacitation and Hyperactivation

• Freshly ejaculated human sperm are not capable of fertilization - A period of time in the female reproductive tract is necessary before sperm can fertilize an oocyte - During their journey, sperm gain the ability to fertilize an egg (a process called sperm capacitation) - Calmodulin, a protein in seminal plasma, may play a role in sperm capacitation - This protein (or another epididymidal secretion) may give the sperm the ability to be capacitated later on when they are in the uterus - Present scientific opinion suggests that capacitation involves removal or modification of molecules (proteins and cholesterol) that stabilize the sperm plasma membrane surrounding the head of the sperm - These molecules suppress the ability of sperm to fertilize - Alteration or removal of these inhibitory molecules destabilize the cell membrane, allowing sperm to respond to signals that trigger the acrosome reaction, an important step in the fertilization process - Capacitation also increases the vigor or tail movements of the sperm (hyperactivation), propelling it toward the egg more effectively - One possibility is that molecules in follicular fluid escaping from the ovulating follicle play a role in sperm capacitation - Follicular fluid contributes only a small part of the oviductal fluid - Studies of mammals have demonstrated that two components of follicular fluid, progesterone and the protein albumin, facilitate the acrosome reaction - Calcium in follicular fluid increases the vigor of sperm tail beating, and an influx of Ca2+ is an essential step in sperm hyperactivation - If components of follicular fluid contribute to sperm capacitation in humans, these substances may have their effect when the sperm penetrates the cumulus oophorus, which surrounds the ovum and is bathed in follicular fluid - A recent discovery is that follicular fluid, or the egg itself, produces a chemical that attracts human sperm - Another study suggests that mammalian sperm move toward the egg along a thermal gradient - The site of fertilization is slightly warmer than more proximal portions of the oviduct, and mature sperm have a preference for moving toward warmer fluid (thermotaxis) - Sperm may be guided by temperature during most of their journey through the fallopian tube and then respond to chemical cues as they near the egg - In the future, we may expand our concept of sperm capacitation to include acquisition of the ability to detect chemical and/or thermal cues

Sperm guidance

• Human egg may produce a chemical that attracts sperm and influences their swimming motion - If follicular fluid from a large Graafian follicle is placed at one end of a chamber, sperm will accumulate at that end, whereas they will not respond to a control fluid - The quantities of estradiol or progesterone in the fluid do not influence this response, but only some and not all follicles have fluid that works - A good correlation also exists between the fertilizability of an egg and the ability of its surrounding fluid to attract sperm - Control fluid previously containing an egg also attracts sperm, so it appears that this signal comes from the egg, not the surrounding follicular cells • When sperm are exposed to the egg signal, they swim in a circle instead of in a straight line, which would increase their chances of contacting the egg - Interestingly, not all sperm are attracted to the egg; some could not care less, and some even swim away from the egg! - A human sperm has at least 20 chemical receptor molecules on its head, and maybe some sperm have not formed the receptor(s) used in this chemical orientation to the egg - Only sperm that have been capacitated can sense chemical cues- so capacitation may expose or activate receptors for the attractant - Recently, human sperm were shown to swim up a gradient of bourgeonal, which is a floral-smelling compound used in perfumes - Human eggs probably don't secrete bourgeonal, but its receptor on sperm cells may recognize some similar molecule released by the egg - Progesterone at low concentrations is also a chemoattractant for sperm • A chemokine called RANTES, secreted by granulosa cells, appears to be an attractant for sperm as well as certain types of blood cells - So the egg may use multiple, redundant cues to attract sperm - Whereas a chemical gradient in the immediate vicinity of the egg may guide the sperm to its final destination, another guidance system may help the sperm to swim in the right direction during its long trip up the fallopian tube - Human sperm respond to a temperature gradient, swimming toward a warmer environment - They have been shown to be sensitive to very small temperature differences - We don't know if human oviduct have a temperature gradient, but in other mammals such as rabbits and pigs, the site of fertilization near the ovarian end of the oviduct is 1- 2°C warmer than the sperm storage region in the isthmus - Perhaps oviductal sperm are guided first by thermotaxis through the long isthmus and then by chemotaxis as they approach the waiting egg

Timing of Fertilization

• Human sperm can live for about six days in the female reproductive tract • An egg's lifespan is much shorter — it is fertilizable for only 24-48h after ovulation • Fertilization can take place - When coitus occurs within a six- day period, i.e. during the five days before ovulation or on the day of ovulation - Most pregnancies occur when sperm are already in the female's oviduct at the time of ovulation

Process of fertilization

• Once a sperm and ovum are in the region of the ampullary- isthmic junction of the oviduct, fertilization can occur - A sperm first penetrates between the cells constituting the cumulus oophorus and then through the zona pellucida and into the perivitelline space - The sperm then enters the oocyte through its cell membrane (the vitelline membrane) - The entire process of fertilization takes about 24 h

Early Pregnancy

• Pregnancy can be wanted or unwanted (or sometimes both) - Whether a woman wants her pregnancy to go to term or not, she should go to a physician, midwife, or clinic two or three weeks after her missed menstrual period - Once there, she will have her medical history taken, including information on the patterns of her menstrual cycles, previous pregnancies, miscarriages, surgery (especially of the pelvic region), childhood diseases, past or present venereal disease infections or other pelvic infections, and general health - Any genetically related disorder in her or in her partner's past should be communicated - The woman should also have a complete pelvic examination for evidence of infection and structure of her pelvis - A Pap smear should be done to check for cervical precancerous or cancerous growth - Her blood and tissue should be tested for sexually transmitted disease, blood type, and diabetes - After the initial visit, most physicians advise a pregnant woman to be checked monthly for the first five or six months of pregnancy - Then, she is examined at least twice a month, until the last months, when she should be seen once a week

Pregnancy Tests

• Pregnancy tests detect a hormone that is present in the blood and urine of a pregnant woman-human chorionic gonadotropin (hCG) - Secreted by the syncytiotrophoblast of the implanting blastocyst and from the placenta soon after pregnancy is established - In the past, bioassays were used to detect the presence of hCG - The current method of detecting pregnancy utilizes a monoclonal antibody to hCG (anti-hCG) • When hCG is present in a solution, anti-hCG combines with it to produce a visible color reaction - In such an immunoassay pregnancy test, anti- hCG and urine are mixed in a test tube or on a glass slide, and the presence or absence of a certain color is noted - This kind of test takes about 2h - A deficiency of this method is that in some cases a color forms when hCG is not present • Due to the interaction of anti- hCG with other proteins in the urine and not to hCG - Also, a negative response can be obtained in a newly pregnant woman • Because the test is done before hCG is secreted in high enough levels to be detected - Most urine tests are not sensitive enough to detect hCG until about 15 days after fertilization (about one day after the missed menses) - Home pregnancy test kits are often less reliable than laboratory results from a clinic or doctor's office • One should be aware of possible inaccuracies in using the quick pregnancy test kits - RIA of hCG in a woman's blood is a very reliable test - hCG can be detected a few days after implantation - However, a limited number of clinics have the facilities to perform this procedure, and it is more costly than the urine method - All these pregnancy tests can give inaccurate results, especially if done in the first two weeks of pregnancy • Not only do the immunoassay tests sometimes give false positives and negatives, but some abnormal kinds of embryonic tissue, such as hydatidiform moles can secrete large amounts of hCG when no embryo is present • Also, a woman with an ectopic pregnancy (in which the blastocyst implants outside the uterus) may not have detectable levels of hCG in her blood • Failure to detect an ectopic pregnancy can be dangerous - a woman should consult with a physician in conjunction with any pregnancy test

Signs of Pregnancy

• Presumptive signs of pregnancy are possible indications of pregnancy - One presumptive sign is a missed menstrual period associated with coitus during the previous month - Secondary amenorrhea is associated with pregnancy - Another presumptive sign of pregnancy is nausea, often after awakening - This is called morning sickness (Box 10.1) and is probably due to a change in stomach function at this time - Morning sickness usually, but not always, goes away in a few weeks - Another possible indication of pregnancy- an increase in the size and tenderness of the breasts, and darkening of the areola surrounding the nipples •Probable signs of pregnancy-in all likelihood, a woman is pregnant - A positive pregnancy test - Uterine cervix becomes softer by the sixth week of pregnancy; this condition, called Hegar's sign, is detected by a physician during a pelvic exam - An increase in the size of the abdomen and an increased frequency of urination (because the growing uterus presses on the urinary bladder) - Positive signs of pregnancy: detection of a fetal heartbeat, feeling the fetus moving, and visualization of the fetus by ultrasound or fetoscopy • Sometimes, a woman with either a great desire for, or a fear of, pregnancy can develop some of these presumptive or even probable signs of pregnancy • This is called false pregnancy (pseudocyesis) and is a good example of how our brain can influence our physiology

Cortical Reaction

• Preventing other sperm from fertilizing the egg - If additional sperm cells were allowed to enter the egg, the extra genetic material they carry would disrupt normal development, and the resulting polyploid embryo would die - Need to prevent polyspermy (fertilization by more than one sperm) - Just underneath the plasma membrane of the egg lie small, membrane- bound vesicles called cortical granules - At fertilization, there is a sudden, dramatic burst in available free calcium in the egg cytoplasm as it is released from cytoplasmic storage - The rise in calcium causes cortical granule membranes to fuse with the adjacent cell membrane - The cortical granules open to the exterior and release their contents into the perivitelline space - Included in the cortical granule contents are enzymes that act on constituents of the zona pellucida - These enzymes alter ZP2 and ZP3, destroying their receptor sites for the sperm head - Subsequently, no additional sperm can attach to the zona pellucida to gain access to the egg

Contents of Seminal Plasma

• Seminal plasma contains several substances, but the precise function of many of these components is not known - Some of them have roles in the maintenance, maturation, and transport of sperm • Water serves as a liquid vehicle for the sperm and seminal plasma constituents • Mucus from the bulbourethral glands serves as a lubricant for the passage of semen through the male reproductive tract • The prostate gland and the bulbourethral glands both secrete buffers, which neutralize the acidity in the male urethra and in the vagina • Some nutrients for sperm are present in the seminal plasma deposited in the vagina, the major one being the sugar fructose (from the seminal vesicles) - Carnitine, concentrated from the blood by the epididymis, is also found in seminal plasma • Involved in the metabolism of fatty acids- metabolites being used as another nutrient source for the sperm - Another constituent of seminal plasma secreted by the epididymis is glycerylphosphocholine • The enzyme diesterase in the uterus hydrolyzes (breaks down) this molecule, and the products of this digestion are used by the sperm as nutrients - Other enzymes secreted by the prostate gland and seminal vesicles are involved in the clotting and subsequent liquefaction of semen in the vagina - Human seminal plasma contains extremely high amounts of zinc (which may have antibacterial activity), and men with low zinc content tend to have a higher incidence of infertility - Some kinds of prostaglandins are secreted into the seminal plasma, mostly by the seminal vesicles • Prostaglandins in seminal plasma may be involved in sperm transport - Finally, seminal plasma contains ATP- men with low semen ATP levels tend to have lower fertility

Formation and Fusion of Sperm and Egg Pronuclei

• Soon after the sperm nucleus enters the egg, its nuclear membrane breaks down - The sperm DNA decondenses as a result of exposure to factors in the egg cytoplasm - A new membrane then forms to enclose the sperm pronucleus - Sperm and egg pronuclei begin to migrate toward each other, replicating their DNA as they move - Their nuclear membranes break down and the two duplicated sets of chromosomes aggregate • Syngamy (merging of the two haploid genomes) has now occurred, and the fertilized egg (zygote) is the beginning of a new diploid individual - In mammals, it takes about 12h from the beginning of egg activation to pronuclear fusion - The centrosome contributed by the sperm organizes a mitotic spindle, and chromosomes now begin to line up at the metaphase plate - The zygote next divides mitotically, and two identical daughter cells, termed blastomeres, are formed (Fig. 9.6) • Embryonic development has commenced - The sperm contributes its haploid chromosomes and centrosome to the zygote - The sperm tail disintegrates in the egg cytoplasm - What happens to the sperm mitochondria? - It has long been known that the approximately 100 mitochondria brought by each sperm into an egg disappear soon after fertilization • During spermatogenesis, sperm mitochondria are tagged with a protein called ubiquitin, a molecule used by all cells to mark proteins slated for destruction • These tagged paternal mitochondria are then destroyed and recycled by the egg after fertilization • Thus, all of our mitochondria are inherited from our mothers • Maternal inheritance of DNA- containing mitochondria has been a useful way to trace human origins

Transport of the Sperm and Ovum in the Oviduct

• Sperm that survive the journey into the fallopian tube find a less hostile environment than in other portions of the female tract - Attack by leukocytes is much reduced - The passage of sperm slows down as the cells encounter mucus in the lumen of the oviduct and have to navigate the increasingly complex folds of the inner lining of the tube - Evidence suggests that sperm heads make contact with and briefly bind to the epithelial cells of the mucosal lining • This contact somehow preserves and extends the viability of the sperm - By slowing down the progress of the sperm, the oviducts may serve as a reservoir from which sperm may gradually proceed, thus extending the time that sperm are available to fertilize an egg - After ovulation, sperm approach the ovum, and fertilization by a single sperm usually occurs at the point where the isthmus joins the wider oviductal ampulla (ampullary- isthmic junction) - Other sperm swim up the ampulla, through the infundibulum, and are lost in the body cavity - Once ovulation has occurred, the infundibulum (funnel-shaped free end) of the oviduct moves toward the ovary and envelops the ovulated ovum along with fluid derived from the ovulated follicle - Movement of the infundibulum is accomplished by the contraction of muscles in the membrane supporting the oviduct - Cilia are present in the wall of the fimbria (the edge of the infundibulum), and these beat toward the uterus - Thus, when the infundibulum envelops the ovary, the beating of the cilia moves the ovum into the ampulla of the oviduct - Cilia in the ampulla and isthmus of the oviduct also beat in a uterine direction, which sets up a flow of fluid toward the uterus - The muscles of the oviduct also exhibit waves of muscular contraction after ovulation - These waves travel in the direction of the uterus and, along with the cilia, help the ovum move down the oviduct - Both ciliary beating and muscular contraction in the oviduct are influenced by ovarian sex hormones - Estrogens increase cilia numbers, and progesterone increases ciliary beating and egg transport - A factor involved in the opposite movement of egg and sperm may be the direction of ciliary beating in the oviduct - Oviductal cilia exist in deep recesses in which cilia beat toward the ovary and on ridges where these cilia beat toward the uterus - Sperm may travel in recesses, whereas the ovum may be propelled along the ridges - The presence of considerable amounts of mucus in the oviducts for three to four days after ovulation may serve as a medium for sperm transport - This mucus is gone when the fertilized ovum (embryo) travels down the oviduct to the uterus

Egg Activation

• The cortical reaction is the first step in a series of biochemical and physical changes in the egg known as egg activation - These rapid changes begin just after fertilization and are preparations for early embryonic development - In addition to the cortical reaction, egg activation involves completion of meiosis, increase in egg metabolism, synthesis of protein, RNA, and DNA, and preparation for the first mitotic division - All of these essential first steps in development are dependent on the initial rise in free calcium - We do not know exactly how fertilization initiates a calcium rise in the egg - One theory (the receptor hypothesis) suggests that binding of a sperm to an egg receptor induces biochemical changes in the egg cytoplasm that cause release of stored calcium - An alternative idea (the cytoplasmic factor hypothesis) is that as the sperm enters the egg cytoplasm, it carries a factor that causes free calcium to be released (Box 9.2) - Laboratory experiments lend support for each of these hypotheses, but the actual mechanism that occurs during normal fertilization remains unknown

Sperm Number and Structure

• The number of sperm in a single ejaculate ranges from 40 million to 500 million (the average is about 182 million sperm) - A male produces about 1 billion sperm for every ovum ovulated by a woman - Many ejaculated sperm (about 30%) are structurally or biochemically abnormal and are either dead or incapable of fertilizing • Reabsorbed by the male or female reproductive tract or are lost through the vagina - For a male to be minimally fertile, his sperm count should be at least 20 million sperm/ml of semen; 40% of these sperm must swim, and 60% should be of normal shape and size - Some evidence shows that human sperm count has declined over recent decades - One study suggests that the sperm count in healthy men has dropped 1% per year in the past 50 years - Other studies contradict this idea - Geographical differences in average sperm count do exist • Differences in sperm production of men living in disparate regions of the world may reflect genetic, cultural, or environmental differences - A healthy human sperm is 60-70 μm long and is composed of the head, neck, midpiece, and tail • The sperm head contains an elongated haploid nucleus surrounded by a nuclear membrane • External to the nucleus is a membrane- bound vesicle called the acrosome •It fits closely over the tip of the sperm head like a cap, and the inner acrosomal membrane lies external to the nuclear membrane while the outer acrosomal membrane is just inside the sperm cell plasma membrane • The acrosome is filled with enzymes important in the fertilization of the ovum • The short sperm neck is followed by the sperm midpiece, which contains mitochondria that generate energy for tail movement • The midpiece and sperm tail represent a flagellum, with the characteristic "9 + 2" arrangement of microtubules •This provides the propulsive force, allowing locomotion of the sperm cell as it moves toward the egg and during egg penetration

Sperm Attachment to the Egg Plasma Membrane

• The sperm approaches the egg sideways instead of head on, and the sperm head now lies parallel to the egg cell surface within the narrow perivitelline space (Fig. 9.5) - At this point, the posterior part of the sperm head attaches to the egg plasma membrane - Plasma membranes of sperm and ovum fuse, forming an opening into which the sperm nucleus, midpiece, and most of the tail sink into the egg cytoplasm - Investigations of the molecules involved in egg- sperm adhesion and subsequent fusion are ongoing • Finding the molecular basis of sperm- egg fusion may help us understand certain forms of infertility and could possibly lead to new contraceptives

Multiple embryos

• Twins occur in about one of every 80 or 90 pregnancies - When two ova are released and each is fertilized by a different sperm, fraternal twins are produced - These twins are dizygotic (the products of two different zygotes) and can be the same or different sex - Fraternal twins, which are nonidentical and are as different from each other as are nontwin brothers and sisters, account for two-thirds of all twins - The incidence of dizygotic twins is influenced by race and by inherited factors from the mother (not the father) - Fraternal twins are more common in older mothers • Identical twins, which are rarer than fraternal twins, occur when an early embryo divides into two - These twins are monozygotic (derived from one zygote) and are identical genetically - The incidence of identical twins is not related to race, inheritance, or age of the mother - Rarely, identical twins are conjoined (i.e. they fail to separate completely during embryonic development) - These are called Siamese twins, after the first publicized Siamese twins, Chang and Eng (1811- 1874), born in Siam (now Thailand) to parents of Chinese heritage • They were united at the chest by a thick mass of flesh • Some conjoined twins have been separated surgically after birth (Chang and Eng could have been easily separated using modern surgical methods)

Tamoxefin are used to treat breast cancer is

antiestrogen

LH receptors are present on

both theca and granulosa cells

what are the three regions or domains of the peptide hormone receptor

g protein coupled receptors 1. extracellular domain 2. ligand hormone binding domain transmembrane domain 3. intracellular domain

true or false: during the menstral cycle the glandular tissue of the mammary glands undergoes enlargement with high estrogen and progesteron levels

true

Maternal Nutrition

• Important for mother's health and to meet additional demands of a rapidly growing fetus and placenta - Requires careful attention to diet, weight gain, and general health - Caloric intake must increase during pregnancy as well as during lactation - Special dietary supplements usually are prescribed such as extra protein, iron, calcium, folic acid, and vitamin B6 - Folic acid, for example, has been shown to reduce neural tube defects in newborns - Under nutrition can harm the fetus, resulting in a low birth weight or even miscarriage

Fetal Evaluation

• It may be desirable to examine the condition of the fetus while it is still within the mother for various reasons - Concern about inherited developmental abnormalities - Fear that the fetus has been exposed to teratogenic or mutagenic substances - Several ways that the condition of the fetus can be scanned • Amniocentesis is usually done when pregnant women are over age 34 and/or have a family history of genetic problems - Performed most often between the 14th and the 16th week of pregnancy - A needle is inserted through the abdominal and uterine wall and into the amniotic fluid, using an ultrasound image as a guide (Fig 10.14) - A small sample of amniotic fluid is then withdrawn for analysis - Because fetal cells are present in the fluid, both these and the fluid itself can be examined - The cells can be cultured in dishes and their structure and function studied • More than 40 genetic abnormalities can be detected by amniocentesis - The sex of the fetus can also be determined by examining the sex chromosomes of the fetal cells - The presence of a neural tube defect such as spina bifida or anencephaly can be detected based on elevated levels of alpha-fetoprotein in the amniotic fluid - During the third trimester, surfactant levels can be measured to assess maturation of the fetal lungs, or the amniotic fluid can be evaluated for the presence of infection - Although this procedure is relatively safe, some studies have shown an increase in uterine hemorrhage, fetal trauma from needle injury, miscarriage, and preterm labor and delivery in babies born to women who have had amniocentesis - Another disadvantage of amniocentesis is that it may take several weeks for the results to be known, and by that time an induced abortion, if desired, is more complex and dangerous - A newer fluorescent in situ hybridization technique can give test results three days after amniocentesis - In certain high- risk pregnancies, the fetus is evaluated by percutaneous umbilical blood sampling or fetal blood sampling - A thin needle is guided through the mother's abdomen and into the umbilical cord, from which a sample of fetal blood is withdrawn - It is used to detect fetal infection, blood disorders such as hemophilia or anemia, certain metabolic disorders, or the presence of chromosomal defects - Because this procedure carries a higher risk of miscarriage than other fetal evaluation methods, its use is limited • Chorionic villus sampling (CVS) - to monitor fetal condition - Used between weeks 8 and 10 of pregnancy • A catheter is inserted through the vagina and cervical canal and into the uterine cavity, using ultrasound as a guide • Chorionic cells are then removed from the placenta and analyzed • Some advantages over amniocentesis because this test can be performed earlier in pregnancy, and one can obtain the results sooner (within 4-24h - Disadvantages of CVS • Fewer tests can be done because there is no amniotic fluid to analyze • Higher risk of miscarriage - The costs of the two procedures are similar • Fetoscopy - more involved and expensive method of fetal scanning - A small incision is made in the abdomen and uterus after injection of a local anesthetic - An optical viewer is then inserted into the uterus, and the fetus is viewed directly - Fetoscopy usually is done from the 15th to the 20th week of pregnancy - There is some risk because fetoscopy causes miscarriage about 5% of the time • Ultrasound to assess the fetal condition - A high-frequency sound source is applied to a pregnant woman's abdomen, and sound waves penetrate to the fetus - Dense fetal tissues, such as bone, reflect the waves, and these are detected by a receiver - Fine measurements of the size and dimensions of the fetus can be made - Fetal heart rate can also be detected as early as the eighth week of pregnancy using ultrasound - The presence of twins can be confirmed - There is some concern but little evidence that ultrasound may affect fetal cells • Multiple serum marker test - noninvasive method used to evaluate the risk of Down syndrome - A sample of the mother's blood is drawn and levels of human chorionic gonadotropin (hCG), maternal serum a-fetoprotein (MSAFP), and unconjugated estriol are measured - A combination of high levels of hCG and low levels of the other two markers indicate a high risk of carrying a Down syndrome fetus, but the test is not definitive - Women at high risk may then confirm the chromosomal abnormality by amniocentesis or chorionic villus sampling • An alternative, noninvasive prenatal diagnostic test takes advantage of the fact that, in most pregnancies, fetal cells and free fetal DNA (not contained within cells) are found in maternal circulation - Blood is drawn from the mother, and fetal and maternal DNA are separated - The fetal DNA can then be screened for genetic abnormalities - This procedure is typically done when a male fetus is present, as male fetal cells can be distinguished from maternal cells based on presence of the Y chromosome

Emergency Contraception

• Normally, ovulation occurs near the middle of the menstrual cycle - The ovulated oocyte must be fertilized within about 24h of ovulation, after which it begins to deteriorate • Sperm can live five to six days in the female reproductive tract • Thus, there is a limited time during which unprotected intercourse can lead to pregnancy • This is the woman's "fertile window" from about five days before ovulation until the day of ovulation • Emergency contraception (also called postcoital contraception or the "morning-after pill") involves the administration of estrogens and/or progestins soon after having unprotected sex - This method prevents ovulation or delays it long enough so the sperm are no longer viable • The popular term "morning-after pill" is misleading, because it is not necessary to wait any length of time before using emergency contraception; the hormones are most effective at preventing pregnancy when taken immediately after unprotected sex - There are more than 20 kinds of pills used for emergency contraception, but only two general types have been marketed specifically for emergency contraception in the US and approved by the FDA • The first is a progestin -only postcoital pill, branded as Plan B or Next Choice- The pill contains a high dose of levonorgestrel, the progestin found in many birth control pills - One (Plan B One- Step) or two (Plan B) pills are taken as soon as possible after having unprotected sex - It can be taken as late as 72h (three days) after unprotected sex, but the contraception is most effective when started as soon as possible within 24 h - This treatment inhibits ovulation - It suppresses the LH surge, but it is not effective after the LH surge and ovulation occur - The best available evidence shows that there is no effect postfertilization, such as transport of the preembryo down the oviduct, or interference with implantation - Thus, emergency contraceptive pills are not effective if a woman is already pregnant; i.e. they do not cause abortion • Failure rates of emergency contraception are generally higher than for contraceptive methods used before or during sex • If taken within 72 h (three days) of unprotected sex, postcoital progestin is 89% effective, but it becomes less effective if taken later, as there is more opportunity for ovulation to occur with a longer waiting time • Side effects may include nausea and vomiting, headache, dizziness, breast tenderness, and change in menstrual flow • In 2009, Plan B (or a generic form) was made available to women and men aged 17 and older without prescription from a pharmacist • In 2013, the FDA approved the marketing of Plan B One-Step, the single-pill treatment, to women age 15 or older over the counter without needing to request the medication from a pharmacist • Another postcoital method of contraception is ulipristal acetate, a selective progesterone receptor modulator that interferes with progesterone signaling in the ovary, hypothalamus, and uterus • Sold under the brand name Ella, it is available by prescription only • Like the progestin - only emergency contraceptives, it works by preventing ovulation, or delays ovulation until the sperm are no longer viable • This method should be used as soon as possible but may be taken up to 120h (five days) after unprotected sex • It is at least as effective as progestin-only emergency contraceptives 72h after unprotected intercourse, and its effectiveness does not appear to diminish up to 120 hours, possibly because it is effective even after the LH surge begins, when progestin-only contraceptives fail to work • Both types of emergency contraceptive pills are somewhat less effective in obese women • Another emergency method is the Yuzpe Method, in which combination pills (estrogen plus a progestin), are taken 12h apart • Relatively large doses of certain brands of combination birth control pills can be used as emergency contraception • Two to five pills are taken within 72h of unprotected sex, and the same dosage is taken again later - Methods using combination pills are simply a new use for some of the combination pills already on the market • One formulation specifically designed for emergency contraception (Preven) contains high levels of estrogen plus progestin in a single pill • Finally, a different type of emergency contraception is the insertion of an IUD up to five days after unprotected intercourse - It is extremely effective (preventing pregnancy 99.9% of the time), making it the most effective method of postcoital contraception - It may be left in place, providing contraceptive protection for up to 10 years

Assisted Reproductive Techniques (ARTs) • In Vitro Fertilization (IVF) - Risks of IVF

• One of the major risk factors-high rate of failure • In 2010, the success rate of cycles in which women used their own, non-frozen eggs was 30.2% - The success rate is better for women under age 35 (41%), and it decreases with every additional year (32% from age 35-37 years, 22% from age 38-40 years, 12% from age 41-42 years, 5% from age 43-44 years, and 1% for women older than 44 years) - Using a woman's own previously frozen eggs, the success rate is 33% per cycle; using donor frozen eggs or embryos, it is 35% • Consider a 36-year- old woman (the average age for an IVF patient) who undergoes an IVF cycle and freezes extra eggs or embryos from that cycle - If she does not become pregnant on the first try, she is likely to use her frozen eggs for a subsequent attempt - This is less expensive and invasive than a full IVF cycle because she does not have to undergo the ovarian stimulation and egg retrieval steps • Each succeeding IVF cycle has a lower probability of success because of the greater failure rate with frozen eggs and also because she is getting older • In 2010, 45% of women having an IVF procedure had attempted one or more previous cycles, and 25% had undergone two or more previous attempts • Despite modest gains in IVF success rates since the CDC began collecting data in 1995, failure can occur at each step of the IVF cycle (Fig.15.2) - The inability of the preembryo to successfully implant is the major reason that IVF cycles fail • In an effort to increase the chance of pregnancy, IVF clinics typically transfer multiple embryos into the uterus • This practice increases the risk of multiple births • Currently, 30% of births resulting from in vitro fertilization using a woman's own, non- frozen eggs are multiples (twins or more) • Using donor eggs, this rises to 39% - Multiple-infant birth rate of only about 3% in the general US population • Multiple births can pose greater potential problems for mother and infants alike - Women carrying multiple fetuses have a greater probability of requiring a cesarean delivery - Infants born from multiple gestations have a higher risk of prematurity, low birth rate, developmental delays, disabilities, and infant death • Although there is no clear evidence overall of an increase in congenital defects in babies conceived through IVF, some studies have reported a higher risk - For example, a recent review found a 67% increased risk of congenital anomalies in infants conceived through IVF - This study also reported a higher incidence of preterm birth, low birthweight, and perinatal mortality associated with IVF • There is a small increased rate of genetic abnormalities in infants conceived using ICSI - This technique is often used when the male partner's sperm count is very low or the sperm lack normal motility, but it is also routinely used in most IVF procedures - Defective sperm are often caused by genetic mistakes, and men using ICSI could pass these genetic errors and their fertility effects to their sons • Pregnancies using IVF have an increased rate of miscarriage

The Endocrinology of Pregnancy

• The endocrine system of a pregnant woman operates differently from that of a nonpregnant woman - Many changes in hormone secretion are adaptations to maintain the fetus and to adapt the body to new nurturing role - The corpus luteum continues to secrete high amounts of progesterone and low amounts of estradiol during the first trimester of pregnancy - This continued activity of the corpus luteum of a pregnant woman supports the decidua and placenta, thus maintaining the pregnancy - Steroids secreted by the corpus luteum of pregnancy also initiate the development of the mammary glands and inhibit ovulation by exerting negative feedback on pituitary gonadotropin secretion - Progesterone also increases fat deposition in early pregnancy by stimulating the appetite and diverting energy stores from sugar to fat • hCG prevents the corpus luteum from regressing and causes it to continue to secrete estradiol and progesterone - Secretion of hCG by cells of the cytotrophoblast begins as soon as 48h after implantation - The rescue of the corpus luteum by hCG is often referred to as the maternal recognition of pregnancy - The human placenta produces GnRH, which may regulate secretion of hCG as it regulates gonadotropin secretion from the anterior pituitary gland - Levels of hCG in the pregnant woman's blood rise steadily, reaching a peak in the second month of pregnancy (Fig. 10.15) - The first hCG peak possibly is responsible for the increase in testosterone secretion in fetal males - Then hCG secretion declines, exhibiting another, smaller rise in late pregnancy (at about 30 weeks) - Even though hCG levels peak in the second month, secretion of steroid hormones from the corpus luteum begins to decline after the second month-the reason for this decline is not known • After about five weeks of pregnancy, the placenta begins secreting three estrogens: estradiol, estrone, and (predominantly) estriol - The placenta also begins secreting progesterone - The secretion of estrogens and progesterone by the placenta is stimulated by hCG - The levels of these steroid hormones from the placenta increase throughout pregnancy, and they continue to support the placenta and mammary glands and to inhibit ovulation - This explains why removal of the ovaries before the seventh week of pregnancy causes miscarriage but not after this time? • The fetus and placenta are both involved in estrogen and progesterone secretion from the placenta - First, the placenta converts cholesterol to progesterone, a conversion that the fetus is not capable of performing - Then, progesterone passes from the placenta to the fetus and reaches the fetal adrenal glands - These fetal glands contain a region called the fetal zone, which is very large but disappears soon after birth - The fetal zone converts progesterone to large amounts of the weak androgen dehydroepiandrosterone (DHEA), which is changed by the fetal liver to 16-OH DHEA-sulfate - Then, 16-OH DHEA- sulfate is carried in the fetal blood back to the placenta to be converted to the estrogen estriol - Secretion of estrogens by the placenta requires the fetal adrenal glands - The fetal adrenals also secrete cortisol, and this hormone can go to the placenta, where it influences estrogen and progesterone secretion - Cortisol may also play a role in initiating labor • In addition to secreting hCG, estrogens, and progesterone, the placenta also secretes a protein hormone that is similar in biological effect to pituitary growth hormone and prolactin- human placental lactogen (hPL) - Rises in the female's blood in late pregnancy and causes an increase in sugar in the mother's blood - Thus, hPL provides the fetus with additional glucose for its growth - The placenta also secretes prolactin, which enters the amniotic fluid - The human placenta may also secrete chorionic corticotropin and thyrotropin, both similar to the pituitary hormones of the same name - Prolactin secretion from the mother's pituitary gland also increases during pregnancy • Relaxin, is secreted by the corpus luteum and placenta - Levels of this polypeptide rise during pregnancy, and it softens the connective tissue connecting the two pubic bones (pubic symphysis) • To facilitate easy passage of the fetus through the birth canal during labor - Relaxin also inhibits premature uterine contractions - The cervix also dilates during early labor, and relaxin helps prepare the cervix for this event - Recently discovered that the placenta produces endorphins (opiate- like natural painkillers) • A woman in late pregnancy may be less sensitive to pain

Sex Ratios

• Given an equal chance of X and Y sperm to fertilize, the sex ratio of embryos should be 100:100 (Fig. 9.7) • However, the ratio of male to female embryos at conception (the primary sex ratio) is estimated to be about 120:100 - This ratio is based on analysis of the sexes of early aborted embryos - This may indicate a greater fertilization rate by Y sperm than X sperm, perhaps because Y sperm are lighter and faster swimmers than X sperm - Alternatively, female embryos may die more frequently than male embryos at a very early stage in development, perhaps before implantation - The sex ratio of male births to female births (the secondary sex ratio) is 105:100 • Thus, for reasons not yet understood, male fetuses suffer a greater mortality than female fetuses in the uterus

Sperm Transport and Maturation in the Female Reproductive Tract

• Sperm are first deposited in the vagina - They pass through the cervix into the uterus, through the junction between the uterus and oviduct (uterotubal junction), and up the isthmus of the oviduct to the usual area of fertilization in the oviduct: the ampullary- isthmic junction - Many of the millions of deposited sperm are lost during this journey, and only about 100- 1000 reach the oviduct, with 20- 200 reaching the egg itself - The sperm must undergo maturational processes during their journey, which give them the capacity to move and to fertilize an ovum • Vaginal Sperm - About 1 min after deposition in the vagina, the semen becomes thicker and less liquid - Semen coagulation is brought about by the enzyme fibrinogenase in the seminal plasma, which converts the protein fibrinogen to fibrin, another protein • The major function of this coagulation may be to prevent sperm loss from the vagina - After about 20 min, the semen again liquefies • This is caused by a fibrinolytic enzyme in the seminal plasma and allows the sperm to swim more rapidly toward the cervix - Even before semen liquefaction, some sperm make it into the cervix and even into the uterus within a few minutes of deposition in the vagina - The environment in the vagina is usually acidic (about pH 4.2), and this level of acidity inhibits sperm motility - Presence of semen in the vagina increases the vaginal pH to a basic 7.2, which in turn increases sperm motility - During coitus, female orgasm is accompanied by muscular contractions of the vaginal walls • These contractions create a pressure in the vagina that is higher than that in the uterus • Sperm movement through the cervix may be aided by this pressure differential • Sperm can move up the female tract even without female orgasm • Cervical Sperm - The cervical canal is lined by a complicated series of narrow folds and crypts and is blocked by a sticky mass of mucus containing long proteins known as mucins (arranged into tiny fibers) • In most stages of the menstrual cycle, the mucus is thick and its fibers are densely packed • Shortly before ovulation the rise in circulating estrogen levels causes the mucus to become more liquid, and some of the mucus proteins reorganize into a more globular shape • This allows gaps though which sperm swim and pass through the cervix at a speed of about 1.2- 3.0mm per minute • Long mucin molecules may also align themselves along the long axis of the cervical canal, forming grooves through which the sperm can travel - If sperm enter the cervix at the correct time of the female cycle, normal sperm are able to move through the cervix, but sperm with abnormal tails or impaired swimming ability are detained • These latter sperm then die and are reabsorbed or lost from the body • Other sperm enter cervical crypts (deep recesses in the cervical wall), where they die or are lost, or they may remain alive as a reservoir of sperm that later may enter the uterus - Fewer than 1 million of the original approximately 200 million sperm make it through the cervix • Uterine Sperm - Upon leaving the cervix, the sperm travel up the uterus to the uterotubal junction • The uterine fluid is watery but sparse in humans, and the sperm essentially "climb" up the uterine lumen by beating their tails • The swimming rate of sperm (about 3 mm/min), however, cannot account for their traveling a distance of about 15 cm in the 30 min after ejaculation • Also, dead sperm reach the oviduct at about the same time as do live sperm • Thus, sperm tail beating probably is not important during sperm transport through the uterus, so it must be the muscle contraction and movement of cilia in the female reproductive tract that facilitate sperm transport - During the later follicular phase, a thin layer of myometrium just underneath the uterine endometrium contracts, directing fluid toward the fallopian tubes - If coitus has occurred, these contractions probably increase - Mechanical stimulation of the cervix by the penis during coitus causes release of the hormone oxytocin from a woman's posterior pituitary gland - This hormone quickly travels via the blood to the uterus and increases the force of rhythmic uterine muscle contractions - These contractions act as waves to help the sperm move to the uterotubal junction - Prostaglandins in the seminal fluid may also cause uterine muscles to contract, but this is unlikely as very little seminal fluid enters the uterus through the cervix • The main function of the prostaglandins in seminal fluid is probably to contract the muscles of the vasa deferentia, thus aiding sperm passage during ejaculation • Vagina, cervix, and uterus respond to the presence of sperm with an immunological attack, and those sperm cells that do not move rapidly through these portions of the reproductive tract are vulnerable to destruction by the female immune system • Arrival of sperm in the uterus initiates a massive invasion of white blood cells (leukocytes) into the uterine lumen • These cells then begin to engulf the dead or dying sperm that have not yet moved up to the uterotubal junction • No more than a few thousand sperm reach this junction - The uterotubal junction is a muscular, tightly constricted region separating the uterus from the oviduct - Sperm enter the narrow opening of this junction and move through it at a relatively slow rate - Thus, the uterotubal junction allows the gradual entrance of sperm into the isthmus of the oviduct - About half of the sperm enter the wrong oviduct, and only a few hundred make it to the general proximity of the waiting egg

Male Infertility • Low Sperm Count

- A low sperm count is the leading cause of infertility in men - An infertile man may have a low sperm count(oligospermia) or the absence of sperm (azoospermia) in the semen • Due to subnormal functioning of the hypothalamus and/or pituitary • Treatment with GnRH stimulatory agonists or gonadotropins may restore fertility in these men • Also, giving the anti- estrogen clomiphene to infertile men can increase their GnRH secretion (by reducing the negative feedback of estradiol on GnRH) and increase fertility - Some infertile men have high prolactin levels in their blood • Treatment with bromocriptine can make them fertile - Sometimes the testes themselves are incapable of responding to gonadotropins • For example, there can be structural abnormalities or permanent damage to the testes • When testes are damaged, the treatment may be artificial insemination of the woman with donor sperm • Some structural problems, however, can be corrected by testicular surgery • Permanent damage could occur because of exposure to radiation or chemotherapy from cancer treatment • Men at risk of infertility from these therapies might consider cryopreserving their sperm before undergoing treatment - May be possible in the future to remove spermatogonial stem cells prior to the cancer treatment - These can be kept alive in the laboratory and reimplanted into the man at a later time, restoring his fertility - A varicose vein in the scrotum(varicocele) can raise testis temperature and cause infertility - Men with retrograde ejaculation have low sperm counts because semen flows into the bladder rather than into the urethra during ejaculation • This condition can arise from previous surgery, diabetes, or certain medications • It can be treated surgically or reversed by stopping the medication - Orchitis, or inflammation of the testis, can cause temporary or permanent infertility • It can result from infection associated with a sexually transmitted disease or other bacterial or viral (usually mumps) infection - Cryptorchid (undescended) testes often are unable to produce sperm -when only one testis is impaired, the other one can usually maintain normal fertility - In about 8-13% of infertile men, the problem is caused by the production of antibodies to their own sperm • This occurs because some sperm inadvertently enter a man's body outside the reproductive tract • Treatment with adrenal hormones has been shown to alleviate this problem in some men - A small number of infertile men have a low sperm count because they are missing part of the Y chromosome

minipill, progestin-only pill

- Before the development of the combination (estrogen plus progestin) pill, the first contraceptive pills contained a progestin only • Both forms of contraceptive are effective, though their biological mechanisms of action differ somewhat • The minipill first was marketed in 1973 as another reversible oral contraceptive measure • This pill contains a low dose of progestin and no estrogen, and it is taken daily without a break • It is available in 28- day packs, and all 28 pills contain the hormone • Because of the lower hormone level, it is essential to take the pill at the same time each day • Menstrual flow may be regular, irregular, or absent when on the minipill, and spotting may occur • It is recommended that a woman use an additional form of contraception during her first one or two months of minipill use because the contraceptive action of this pill may take a while to be effective - The minipill blocks ovulation in about 50% of women- its major effect is to render the cervical mucus hostile to sperm transport • It also causes the endometrium to be thin and not conducive to implantation • One advantage of this pill over the combination pill is that there are fewer adverse side effects, although there is an increase in breakthrough bleeding, variation in cycle length, amenorrhea, and risk of ectopic pregnancy in the case of contraceptive failure • Also, the failure rate of the minipill is somewhat higher than that of the combination pill • For these reasons, use of the minipill is not widespread • Progestin- only pills are a good choice for nursing mothers who should not use estrogens

Embryonic and Fetal Development • The Embryonic Period

- By the end of the 2nd week of postfertilization development, the preembryo has undergone gastrulation and is now a flattened disc consisting of the three germ layers: ectoderm, mesoderm, and endoderm • The next six weeks constitute the embryonic period, in which all of the major internal and external structures take shape • This is an extremely important period of development • It is also very sensitive to disturbances, and any alteration in development during this period may lead to death or major congenital malformations (Fig. 10.13) - During the 3rd week of development, the flat, trilaminar embryonic disc begins to curl under to form a sausage- like shape - This movement places the ectodermal layer on the outside, the endoderm lining the inner tube (which will form the gut tube) and mesodermal tissue sandwiched between the other two layers - A neural tube develops along the embryo's back and gives rise to the brain and spinal cord (CNS) - The brain begins to enlarge in the future head end of the embryo - A series of lumps, the somites, form along either side of the neural tube • These will develop into the vertebrae, ribs, and muscles of the back - At the beginning of the 4th week, the embryo is about 2mm in length - As the head and tail ends begin to curl in, the embryo assumes a C shape - In the head, the eyes begin to form and, more posteriorly, otic pits mark the position of the future inner ears - The neck region expands and a series of lumps can be seen; these are the pharyngeal arches that will develop into jaws, parts of the ear, and other structures - Underneath the pharyngeal arches, the heart forms a prominent bulge and begins beating - Tiny arm and leg buds begin to swell. By the end of the week, the embryo has doubled in length - Rapid growth of the brain occurs in the 5th week - This brain expansion is so extensive that the embryo's head bumps into its heart! - The arm buds begin to flatten, and the hands become paddle shaped - The embryo is about 1cm in length at the end of this week - During the 6th week of development, the eyes become pigmented and more obvious - The external ears begin to form - Expansion of the brain and head continues, and the head now constitutes approximately half of the embryo - The leg bud becomes paddle shaped, and indentations in the hand bud called finger rays indicate the position of the digits - A distinct tail is still present - In the 7th week, toe rays form - Rapid development of the gut tube causes intestines to protrude into the umbilical cord, which is evident as a swelling of the umbilical cord (umbilical herniation) - By the end of the 8th and final week of embryonic development, the embryo has grown to a length of 1.25in - The eyelids have grown to meet each other and fuse; thus the eyes are now closed - Fingers and toes can be seen clearly, but a thin sheet of webbing still exists between each digit - The tail bud has disappeared, and the embryo now begins to look distinctly human

Fetal Disorders • Rhesus Disease

- Commonly called "Rh incompatibility," Rhesus disease is an inherited phenomenon that damages not the present fetus but the fetus of a future pregnancy - This disease involves a gene with a dominant allele (R) and a recessive allele (r) for the Rhesus factor - Thus, cells of an individual can be Rh+ (RR or Rr) or Rh− (rr) - The cause for concern is when the pregnant woman is Rh− and the father is Rh+, which occurs in about 10% of marriages - In this situation, the Rh− woman could be carrying an Rh+ fetus - During labor and delivery, fetal blood cells could enter the maternal tissues because of broken blood vessels as the placenta detaches (Chapter 11) - Because the mother's tissues are Rh− and the fetal blood cells are Rh+, she will form antibodies to the fetal Rh+ cells - If she then becomes pregnant again with an Rh+ baby, these antibodies will enter the second fetus and destroy its mature red blood cells - As fetal red blood cells are destroyed, the fetus will develop jaundice (yellowish skin) due to the accumulation of bilirubin (a breakdown product of red blood cells) in its tissues - Bilirubin is toxic and can cause brain damage - Also, because mature fetal red blood cells are attacked, there will be many new immature red blood cells (erythroblasts) in the fetal blood, a condition termed erythroblastosis fetalis - Because these immature red blood cells are not efficient in carrying oxygen, the fetus is anemic and its tissues are unable to grow properly - In the past, it was necessary to give a complete blood transfusion to a newborn with Rhesus disease - Current treatment, however, is much safer • An injection of Rhogam or Rho Immune (antibodies to Rh factor) is given to the mother within two or three days of delivery of the first infant or of a miscarriage or induced abortion • This drug destroys all Rh+ fetal red blood cells that may have entered her blood, and thus she does not form antibodies that could harm her future fetus

Use of the Combination • Beneficial side effects

- Despite these potentially harmful effects of the combination pill, the death rate from pill use is still less than that resulting from pregnancy and childbirth • Women using the pill have a decreased incidence of ovarian cancer, with a 20% lower risk after five years • The protective effect is increased with longer pill use and continues for years and even decades after use of the pill is discontinued • The combination pill also lowers the risk of endometrial cancer and, as with ovarian cancer, the protective effect increases with length of pill use, and protection continues after a woman stops using the pill • Studies also indicate that pill use protects against colorectal cancer • Women who take combined oral contraceptives are at decreased risk for pelvic inflammatory disease - Other beneficial side effects of the combination pill are alleviation of acne, excess body hair, breast cysts, heavy and irregular menstrual periods, menstrual pain and symptoms of endometriosis, and premenstrual syndrome • The monthly menstrual flow is more regular and averages less in volume in pill users than in nonusers- often less severe cramping and menstrual pain • The pill can also protect against anemia in women who experience heavy loss of blood in the menstrual flow • Finally, the combination pill can be used to treat endometriosis and uterine fibroids • In fact, 14% of contraceptive users in the US report that they take these hormones for noncontraceptive use alone

Drugs, Alcohol, and Tobacco

- During pregnancy, especially in the first trimester, a woman should ask her physician about any medication she is taking or considering taking, including nonpresscription drugs - For example, taking the drug pseudoephedrine, a component of decongestant medicines and nasal sprays, can cause a baby to be born with gastroschisis, a condition in which there is a hole in the abdominal wall through which the intestines protrude - Thalidomide is a mild tranquilizer that was used to treat morning sickness and to stop bleeding in pregnant women in the late 1950s and early 1960s, mostly in Europe and Canada - From 1958 through 1961, several thousand severely deformed infants were born to women who used this drug during pregnancy, especially during the 4th through the 7th weeks of pregnancy - Thalidomide causes the fetus to develop hands and feet but not arms or legs, a condition called phocomelia, or other abnormalities such as the total absence of limbs (ectromelia) - From the 1940s until the early 1970s, a synthetic estrogen, diethylstilbestrol (DES), was given to pregnant women to prevent miscarriage - About 2 million women in the United States were exposed to the drug during the first trimester of pregnancy - In the early 1970s, it was found that daughters born to these women exhibited an increased incidence of vaginal and cervical cancer, as well as an increase in miscarriage and premature births - Some of the sons born to these women also developed abnormalities in the male reproductive tract, including undescended testes and a low sperm count in their semen - DES is no longer given to pregnant women - Alcohol ingested by a pregnant woman can cross the placenta and adversely affect fetal development • Having at least two alcoholic drinks a week during early pregnancy can increase the risk of miscarriage • Chronic use of alcohol (more than 3 oz of alcohol daily) produces fetal alcohol syndrome 30 - 45% of the time • This syndrome is the leading cause of mental retardation in infants in the United States today • It is characterized by the birth of relatively small infants with small heads • These children usually have delayed mental development as well as learning disabilities and behavioral problems • Milder alcohol intake (1-2 oz daily) can constrict umbilical blood vessels and cause miscarriage or the birth of an abnormally small infant - It has been shown that about three alcoholic drinks a day late in pregnancy can cause a reduction in IQ test performance in children at four years of age • Even small amounts of alcohol during gestation could harm a fetus, and no level of alcohol use during pregnancy has been proven safe - Narcotics such as heroin and methadone, as well as cocaine, will cross the placenta and can cause addiction of the newborn • Lysergic acid diethylamide (LSD) can also cross the placenta and damage the fetal chromosomes, leading to deformities • In addition to reducing fertility, marijuana smoking (exposure to tetrahydrocannabinol) can decrease estrogen secretion from the placenta and cause miscarriage - Tobacco smoking can have adverse affects on the fetus in several ways • First, the nicotine in tobacco smoke constricts blood vessels in the placenta and fetus, resulting in poor delivery of such blood-borne substances as oxygen and glucose to the fetal tissues • The carbon monoxide in tobacco smoke can bind to the hemoglobin of fetal red blood cells, thus preventing the oxygen from binding • Tobacco smoking during pregnancy can lower vitamin C levels in the fetus, impair fetal growth, and lead to miscarriage, premature birth, or stillbirth • Smoking can also damage the part of the brain that will control respiration in the infant, and some instances of crib death may be related to the mother's smoking during pregnancy • Some children of mothers who smoked during pregnancy have hearing difficulties and lower IQ tests • It is recommended that a woman not smoke while pregnant - Some evidence in laboratory mammals suggests that ingesting high levels of caffeine also could harm the fetus - In humans, studies of the possible effects of caffeine intake during pregnancy have yielded conflicting results - Although some studies have indicated no adverse effects of caffeine on human fetal development, several others demonstrate that caffeine consumption during pregnancy is associated with a higher risk of miscarriage - It is clear that caffeine crosses the placenta, and because caffeine is metabolized more slowly during pregnancy, a pregnant woman may have higher caffeine blood levels than a nonpregnant woman with the same caffeine intake - Ingestion of aspirin, ibuprofen, or indomethacin by a pregnant woman can harm the fetal heart - The ductus arteriosus of the fetal heart is kept open by the secretion of prostaglandins, and these drugs are antiprostaglandins - Thus, exposure of the fetus can partially close the ductus arteriosus, resulting in babies born with poorly oxygenated blood and bluish skin (cyanosis) - Because the ductus arteriosus is partially closed in these fetuses, too much blood is pumped into the vessels of the still-collapsed fetal lungs - This thickens the walls of the fetal lung blood vessels and can lead to persistent pulmonary hypertension, a condition in the newborn in which the arteries in the lungs have thick walls, and blood cannot pass through the lungs as well as it should - About two tablets of aspirin, ibuprofen, or indomethacin a day for four or five days in a row is too much during pregnancy - Acetaminophen, a non-prescription aspirin substitute, has only slight antiprostaglandin activity and therefore is probably safer than aspirin during pregnancy - Studies suggest that excess vitamin A ingested by a pregnant woman, especially in the first trimester, can increase birth defects of the face, head, brain, and heart • Anything above the recommended adult daily intake of vitamin A (2700 IU/day) is too much, and some multiple vitamins contain 10,000 IU per pill! - Use of antidepressant Prozac (fluoxetine) has been shown to increase the risk of minor birth defects (such as fused toes) as well as premature delivery

Transdermal Hormone Delivery

- Estrogens and progestins can be delivered across the skin (transdermally) through the contraceptive patch, which is currently marketed in the United States as Ortho Evra • The estrogen in this patch is ethinyl estradiol; the progestin is norelgestromin • The thin plastic patch is worn on the skin, where it provides a constant flow of these hormones into the bloodstream • A woman places the patch on her torso, stomach, buttocks, or upper arm • Because it is highly adhesive, women can bathe, swim, and carry on normal activities while wearing the patch • It should be applied once a week for three weeks-important to remember to apply the patch on the same day for the three consecutive weeks • The fourth week is patch free, and menstruation occurs at this time - The patch appears to be as effective as the combination pill in preventing pregnancy • Like other combination hormonal contraceptive methods, the patch works primarily by preventing ovulation • In addition, thickening of the cervical mucus inhibits sperm movement • Advantages include convenience and ease of use; there is no daily pill to take, no injections, and a woman can apply the patch herself • Side effects are similar to those of the combination birth control pill - Some women experience skin irritation at the application site

Teratogens, mutagens, & other agents that damage fetuses

- Exposure of the embryo or fetus to certain drugs, chemicals, or radiation can be mutagenic (damaging the genes or chromosomes of fetal cells) or teratogenic (affecting fetal growth and development) - These exposures can also cause loss of a pregnancy (miscarriage, or spontaneous abortion) or birth of a dead fetus (stillbirth)

The Process of Pregnancy • Implantation

- Fertilization usually occurs in the ampullary- isthmic portion of the oviduct - Then the dividing ball of cells moves down the oviduct and into the uterus, where it implants in the uterine wall • The zygote undergoes several cleavage (mitotic) divisions to become a ball of approximately 32 cells by the third day after fertilization. This solid ball of cells is called a morula (Latin for "mulberry"), as shown in Figure 10.1 • The zona pellucida, which originally surrounded the oocyte within the follicle before ovulation, remains as a translucent membrane surrounding the morula • The morula continues dividing as it passes down the oviduct to the uterotubal junction (Fig.10.2) • It is assisted in its journey by the relative absence of oviductal mucus at this stage and by the beating of oviductal cilia in a uterine direction - At about three to four days after fertilization, the preembryo enters the uterus (Figure 10.2) • Now, it is a larger mass of cells called a blastocyst (Fig. 10.1) - From the outside, the blastocyst looks like a solid ball of cells • If it is cut in half, a fluid-filled cavity, the blastocoel, is revealed - A single layer of cells, the trophoblast, forms the outer layer of the blastocyst just inside the zona pellucida (Fig.10.1) - A clump of cells near one end of the blastocyst underneath the trophoblast layer is called the inner cell mass (Fig. 10.1) - This group of cells gives rise to the embryo - It is also the source of embryonic stem cells (Chapter 15) - The blastocyst rests freely in the uterine cavity for about two or three days, during which time it derives nutrients secreted by the uterine glands and increases slightly in size - On about the sixth day after fertilization, the uterus secretes an enzyme (protease) that dissolves the zona pellucida surrounding the blastocyst - Once the blastocyst has "hatched" out of the zona pellucida, the inner cell mass end of the blastocyst attaches to the uterine wall - The blastocyst then begins to invade the endometrium, a process called implantation - Implantation begins 7-10 days after fertilization and usually occurs on the posterior wall of the fundus or corpus of the uterus - During the early phases of implantation, the trophoblast differentiates into an outer syncytiotrophoblast and an inner cytotrophoblast (Fig.10.3) - The syncytiotrophoblast secretes proteases that break down cells of the uterine endometrium, thus allowing the blastocyst to penetrate into the uterine stroma - The syncytiotrophoblast acquires its name from the fact that it consists of a mass of cells that have lost their cell membranes and have communicating cytoplasm; such a structure is called a syncytium - Meanwhile, cells in the uterine stroma (the connective tissue framework of the uterus) multiply rapidly and form a cup that grows over the blastocyst - This growth of uterine stromal cells is called the deciduoma response - Implantation is now complete - The conceptus has invaded its mother's endometrium and will now live off nutrients in the maternal bloodstream - In turn, the maternal tissue has cooperated to allow a controlled, limited incursion - As in all delicate negotiations, this complex, coordinated interaction between the conceptus and maternal tissues is possible only through communication - Researchers are now working to decipher the chemical signals (such as growth factors and other proteins) released by the conceptus and the maternal endometrium during implantation - If implantation does not occur, the blastocyst will degenerate and pregnancy will not occur • Implantation requires a uterus that has been exposed to just the right amounts of E2 and P4 at the right time. • Corpus luteum formed after ovulation secretes moderate levels of E2 and higher amounts of P4. • This ratio of steroid hormones primes the uterus, making the endometrium vascular, secretory, and ready for implantation • P4 also causes the uterus to secrete the protease that dissolves the zona pellucida surrounding the blastocyst • Implantation also requires the active participation of the blastocyst - A blastocyst poised for implantation releases signaling molecules that participate in a reciprocal "conversation" between blastocyst and endometrium that allows the process to proceed normally - A fetus's cells are genetically different from those of the mother (Box10.2) - If doctors were to transplant a genetically different tissue or organ into a woman's body, her immune system would recognize the tissue as "foreign" and attack and reject it - When she becomes pregnant, her fetus acts as an invading foreign parasite that one would expect her body to reject just as vigorously - However, for nine months, the maternal immune system holds off the attack - One possibility is that the fetus might somehow escape detection by the mother's immune cells - Alternatively, pregnancy may suppress the maternal immune system - The answer is not clear, but it may involve aspects of both of these mechanisms - The external layer of the blastocyst is the trophoblast, which makes contact with the uterine epithelium as implantation begins - The syncytiotrophoblast, which develops as the outermost layer of the trophoblast, aggressively burrows into the uterine wall until the embryo is completely embedded in maternal tissue - This syncytiotrophoblast encloses the developing embryo and is the only embryonic tissue in direct contact with maternal tissue throughout pregnancy - It later forms the external layer of the placenta - Thus, the placenta is the front line of maternal/fetal interaction - A woman's body can detect the presence of foreign cells because cell surface histocompatibility proteins called human leukocyte antigens (HLAs) "present" foreign antigens to her immune cells • These HLAs are found on most nucleated cells • However, placental cells largely lack the most common HLAs • Instead, the surface of placental cells is studded with a unique molecule, HLA-G, not present in other cells of the mother or fetus • The mother may not recognize these particular histocompatibility molecules as "foreign," thus helping the fetus evade detection by the maternal immune system - There is little evidence that the maternal immune system is suppressed overall during pregnancy - Pregnant women can successfully fight off colds, flu, and other common infections - However, those women with autoimmune diseases can experience more severe symptoms (e.g. lupus) or their symptoms can be alleviated during pregnancy (e.g. rheumatoid arthritis) - This reflects a shift in the relative importance of cell - mediated and antibody defense systems during pregnancy - Changes in circulating levels of progesterone, prostaglandins, and other hormones likely induce alterations in the maternal immune system - Some evidence also shows local changes in the immune response within the uterus - A woman's immune system is altered but not disabled during pregnancy - Fetal cells can occasionally slip across the placental barrier and make their way into the mother's bloodstream - For some reason, some of these cells escape being killed and can multiply and persist in the maternal circulation for decades (Box10.3) - Whether the presence of these roaming fetal cells influences the mother's immune response to her fetus is not known

Male Infertility • Sperm Transport

- In some infertile men, the secondary accessory ducts or glands are not functioning properly • The vasa deferentia, for example, can be occluded by an enlarged testicular vein pressing on it (varicocele) • The vasa can also be blocked by scar tissue caused by sexually transmitted infection • Many of these cases can be corrected with surgery - A sex accessory gland may be malfunctioning or inactive • If the glands are simply underdeveloped, this condition can be treated by the administration of an androgen - Infection of the prostate can lead to sterility in some men - Erectile dysfunction can also result in infertility • Some types of erectile dysfunction can be treated

Female Infertility • Tubal Blockage

- In some infertile women, ovulation occurs but the sperm fail to reach the egg, or the fertilized egg cannot reach the uterus because of a blockage in one or both oviducts • Tubal blockage is the second leading cause of infertility in females, occurring in 30-35% of infertile women • Can be caused by a kink in the tube or by scarring as a result of past sexually transmitted disease infection (especially chlamydia) that caused pelvic inflammatory disease (Chapter17) • Also, if a woman has suffered from endometriosis, a piece of the uterine endometrium may have become displaced from the uterus and lodged in the oviduct • This can cause sterility because the uterine tissue grows and blocks the tubes • Endometriosis can also cause infertility when the tissue does not block the tubes but is present outside the tubes or in the abdominal cavity, especially around the ovaries - Tubal blockage sometimes can be repaired by introducing a fluid or gas (CO2 or air) into the tubes • The tubes can be inspected by laparotomy or laparoscopy and combined with the use of instruments to remove adhesions • Also, a small balloon can be inserted into the obstructed tube, and when it is expanded the tube is unblocked- transcervical balloon tuboplasty • If this fails to open the tubes, it may be possible to repair them surgically • Women with fallopian tube blockages can use in vitro fertilization (IVF) to bypass the oviducts in an attempt to achieve pregnancy; IVF is now more common than tubal surgery

Female Infertility • Failure to ovulate is the leading cause of infertility in females

- Irregular or absent menstrual periods can be a sign of ovulation problems • Hypothalamus or pituitary gland may not be fully functional, such as in case of a pituitary tumor • Severe stress, excessive exercise, or extremes of body fat can cause failure to ovulate • Hypothalamus may not be secreting enough GnRH to stimulate an LH and FSH surge that results in ovulation • In this case, administration of GnRH stimulatory agonists in small dosages has been effective in inducing ovulation • A small pump can be placed under the skin, which slowly releases GnRH pulses into the bloodstream - Not enough LH and FSH secretion from the pituitary even though adequate levels of GnRH are present • One common treatment in this case is the drug clomiphene (Clomid)-administered orally • Clomiphene is an anti- estrogen that inhibits the negative feedback action of estrogens on FSH and LH secretion • FSH and LH levels increase when clomiphene is given, and follicles develop sufficiently to be ovulated • Between 60% and 80% of infertile women so treated will ovulate, and about 50% will become pregnant • It is usually prescribed as a 5-day treatment during the follicular phase, starting a few days after the beginning of the menstrual flow (if present) • Because it is relatively inexpensive, effective, and can be taken orally, clomiphene is often the first- order treatment for anovulation • One effect of clomiphene is that the chance of having twins is 5% compared with 1% in untreated women • Increased gonadotropin levels can hyperstimulate the ovary, causing ovulation of two eggs - dizygotic (fraternal) twins • Other side effects can include hot flashes, mood swings, headaches, visual disturbances, and ovarian cysts • Although women with certain kinds of infertility may be at increased risk for ovarian cancer, the use of clomiphene does not appear to affect this risk - Another treatment for a woman who is secreting insufficient FSH and LH is the administration of gonadotropins • FSH injections can be used to boost the levels of this gonadotropin • More commonly, human menopausal gonadotropin (hMG; e.g. Pergonal), which contains FSH and LH, followed by human chorionic gonadotropin (hCG; Fig. 15.1), is prescribed • These gonadotropins are administered as injections • This treatment causes ovulation in 50-70% of cases- highly effective • The incidence of twins is 15%; for triplets or more, it is 5% • For these reasons, gonadotropin treatment is used only as a last resort unless, of course, twins or triplets are desired - Some women using hMG and other fertility drugs develop abdominal pain caused by enlargement of the ovaries - This ovarian hyperstimulation syndrome can cause mild symptoms, but cases with severe pain, bloating, and shortness of breath require immediate medical attention

Bacterial STDs • Chlamedia

- Most common sexually transmitted bacterial infection caused by the gram-negative bacterium Chlamydia trachomatis - A member of a group of very small bacteria that live inside cells and were once thought to be viruses • Chlamydia can be spread from the penis, vagina, anus, or mouth of an infected sexual partner • These bacteria infect mucus membranes and can cause infection of the cervix in women and infection of the urethra, anus, and mouth in both sexes • Chlamydia can also be passed to the eyes by touching infected regions • At present, there are close to 3 million new cases of chlamydia each year in the US (Fig.17.1) • Young people are disproportionately affected; it is estimated that 1 in 15 sexually active teenage females has a chlamydia infection - In females, the cervix is the main site of chlamydia infection, sometimes leading to a yellowish vaginal discharge, spotting between periods, and frequent urination • The cervix, vagina, urethra, and vulva can become reddened and irritated • Although chlamydia can be easily diagnosed and treated, most infected individuals have no symptoms; therefore, they do not seek treatment for themselves and unknowingly pass the infection to their sexual partner(s) • A persistent infection can result in serious health consequences, especially for women • Between 70% and 95% of infected women have no symptoms, making it difficult to detect and treat these infections • An untreated infection can spread from the cervix to the uterus and oviducts, causing pelvic inflammatory disease, damage to the oviducts, chronic pelvic pain, and even infertility - It is estimated that about 11,000 women in the United States become infertile annually as a result of chlamydia infection • A chlamydia infection in a pregnant woman can be passed to her child during delivery, which can result in lung (pneumonia) and eye (conjunctivitis) infections in the newborn - Male partners of chlamydia- infected women or men usually have chlamydia in their bodies • Although 90% of these men are asymptomatic, some infected men develop frequent and painful urination; more rarely, the testes become inflamed and tender or painful • For men, the incubation period is 7-28 days • In both men and women, chlamydial infection increases the risk of infection by HIV by three-to five -fold for those exposed to the virus • Correct use of latex condoms can reduce the risk of passing chlamydia to a sexual partner - CDC now recommends that all sexually active females under the age of 25, as well as those over 25 who have a new sex partner or multiple sex partners, be screened for chlamydia at least once a year • Pregnant women should be tested at least once during their pregnancies • Chlamydia is detected by tissue culture, an enzyme test, and a DNA assay • For both sexes, chlamydia can be cured by treatment with antibiotics such as azithromycin or doxycycline • Both partners should be treated, even if only one has symptoms • Women whose partners are not treated are at high risk for reinfection • All sexually active people are at risk for chlamydia infection, but being in a mutually monogamous relationship with an uninfected partner, as well as consistent use of condoms, greatly reduce the risk of infection

Maternal Estrogen and Progesterone

- Progesterone domination for most of pregnancy causes the myometrium to be noncontractile • P4 inhibits the synthesis of prostaglandins and receptors for oxytocin; both of these hormones cause myometrial contractions • Myometrial contractions require calcium, and progesterone downregulates the development of calcium channels in uterine tissue • In contrast, estrogens oppose the actions of P4 and increase the ability of the uterus to function as a coordinated contractile organ • Estrogens stimulate the synthesis of prostaglandins that cause the uterus to contract • In addition, estrogens induce the formation of oxytocin receptors in the myometrium and increase gap junctions connecting myometrial smooth muscle cells, coordinating contractions of individual cells, and allowing the uterus to contract efficiently to expel the fetus - Finally, estrogens promote the softening of collagen in the cervix, resulting in cervical "ripening' that allows expansion of the cervix as the fetus passes through the birth canal • In pregnant women, there is no sharp rise in E2 or drop in P4 prior to birth as seen in many other mammals • However, in the last 4-6 weeks of pregnancy, the E/P ratio of pregnant women rises slightly because of increased estriol production by the placenta • P4 levels remain constant, although the uterus may become less responsive to P4 near the end of pregnancy • This increase in E/P ratio may thus promote conditions leading to uterine contractions • The human placenta is not capable of converting P4 to estriol • Instead, placental P4 is first sent to the fetal adrenal gland, which uses it to synthesize dehydroepiandrosterone sulfate (DHEA-S), a weak androgen, which then returns to the placenta to be converted into estriol (Fig.10.16) • Rising CRH at the end of pregnancy stimulates the fetal adrenal to produce DHEA-S, and in response, the placenta increases its synthesis of estriol (Figure11.3)

The Combination Pill

- Research on laboratory mammals clarified that a certain ratio of the levels of estrogen and progestin in the blood during the luteal phase of the estrous cycle blocks ovulation - The three natural estrogens (estradiol- 17β, estriol, and estrone) were identified in 1929 and 1930, and the natural progestin (progesterone) was identified in 1934 - In 1937 Sir Charles Dodd synthesized an artificial estrogen (stilbestrol), which was followed by the introduction of more synthetic estrogens such as ethinyl estradiol and synthetic progestins such as ethisterone and norethynodrel • An important development in the 1940s was the finding by Russell Marker that the Mexican yam was an inexpensive source of the material needed to make synthetic steroid hormones • The idea of human steroidal contraception and an inexpensive source of synthetic steroid hormones, was available by 1950 - By the mid-1950s, Gregory Pincus, as well as John Rock and Celso-Ramon Garcia, began clinical investigations on the effectiveness of the progestin norethynodrel as a contraceptive agent - In 1956 in Puerto Rico, John Rock, Gregory Pincus, and Edris Rice-Wray, a feminist and birth control advocate, began clinical trials of norethynodrel in pill form • The original preparation of norethynodrel contained small amounts of mestranol, an estrogen, and it was discovered that the presence of this estrogen decreased the side effects of the pill • Thus, in 1960, the US Food and Drug Administration (FDA) approved the use and marketing of the combined oral contraception (COC) (or combination pill) containing progestin plus an estrogen - This first combination pill (Enovid) contained 10 mg of norethynodrel (progestin) and 150 μg of mestranol (estrogen) - By 1963 the progestin content was reduced to 2 mg or less and the estrogen to 100 μg or less, and today's combined oral contraceptives typically contain no more than 35μg estrogen • The combination pill (often referred to simply as "the Pill") became a popular contraceptive measure in the US and other parts of the world • Although not all women are good candidates for use of the pill, the combination pill is still the most commonly used reversible contraceptive method in the US and is taken by over 100 million women worldwide

Male Infertility • Environmental Factors

- Some men can be temporarily infertile because of environmental factors • Smoking, for example, can decrease sperm motility and increase the number of structurally abnormal sperm in the ejaculate • Testosterone levels in the blood are also lower in men who smoke • Accumulation of some environmental pollutants including heavy metals, industrial chemicals, and endocrine disrupters such as xenoestrogens can also reduce sperm count • Chronic use of some drugs, such as alcohol, marijuana, and anabolic steroids, can also reduce fertility • Certain medical conditions, including obesity, diabetes, and thyroid disease, can reduce a man's fertility, and a gradual decline in fertility often occurs after age 35 • Heat, such as from frequent hot baths or saunas or from wearing tight clothing, can temporarily lower sperm count

viruses and bacteria

- Some viruses can severely damage or kill the embryo or fetus • AIDS, smallpox, chickenpox, mumps, and herpes • The German measles (rubella) virus can produce heart defects, blindness (due to cataracts), deafness, microcephaly (small brain), mental deficiency, cleft palate, harelip, and spina bifida (exposed spinal cord) • Exposure of the fetus to the rubella virus is most damaging from the 3rd to the 12th week of pregnancy • Before this time, little or no damage occurs • To prevent exposure of future fetuses to rubella, females should be exposed to the virus to form antibodies while they are still children, either by naturally contracting the disease or by vaccination • Bacterial infections such as syphilis, pneumonia, tuberculosis, and typhoid can cause spontaneous abortion

The Process of Pregnancy • Early Embryonic Development

- Soon after implantation, the inner cell mass differentiates into two layers of cells, the epiblast and the hypoblast (Fig.10.3) - This two-layered structure is called the bilaminar embryonic disc, although only one of the layers (the epiblast) will give rise to cells of the embryo proper - The next essential step in development is gastrulation, in which epiblast splits into three germ layers: ectoderm, mesoderm, and endoderm, pushing aside the hypoblast - Cells arising from the ectodermal layer will form the nervous system of the embryo, as well as the epidermis (outer layer) of the skin and related structures such as hair, nails, and tooth enamel - The mesodermal layer gives rise to many internal structures, including the skeleton, muscles, the circulatory system, the deep (dermal) layer of the skin, the kidneys and gonads, and the notochord, a longitudinal rod supporting the back of the early embryos that is later replaced by the vertebral column - The endodermal layer differentiates into the lining of the digestive tube and of all of the structures that bud off of the early gut tube, including the liver, gall bladder, pancreas, and respiratory tube including the lungs • Thus, all of the cells in an individual's body originate in the epiblast layer • The hypoblast, along with cells from the epiblast and the trophoblast, contributes to the extraembryonic membranes • These tissues sustain the embryo during intrauterine development, but eventually degenerate or are shed at birth

Female Infertility • Reduced Sperm Transport or Antibodies to Sperm

- The female tract may not allow transport or survival of the male's sperm - The woman's vagina may be overly acidic, which can be treated using alkaline douches - Alternatively, her cervical mucus may be hostile to sperm movement, a condition perhaps alleviated by estrogen administration - If the cervix has been damaged, as sometimes occurs as a result of infection, this damage may be corrected surgically - In some cases, a woman produces antibodies to her husband's sperm, and in this case the couple may choose to become pregnant using donor artificial insemination

Embryonic and Fetal Development • The Fetal Period

- The fetal period begins at week nine of postfertilization development and extends until birth • The organ systems established in the embryonic period continue to develop and differentiate • A period of increasingly rapid growth - By the end of the first trimester (12 weeks of development), the fetal heartbeat can be detected with a stethoscope • The fetus can react to stimuli and fetal movements begin, although the mother cannot feel these movements until the fourth or fifth month (halfway through pregnancy) - By the end of the second trimester, the delicate fetal skin is covered with a protective layer of fatty secretions called vernix caseosa - The skin grows a layer of downy hair (lanugo), which usually is shed before birth - During the third trimester (weeks 25- 38 of development), the fetus adds layers of fat and loses its wrinkled appearance • The lungs mature toward the end of this trimester • The fetus has a possibility of surviving if born after 26 weeks • But would need advanced medical intervention

Subdermal Progestin Implants

- When swallowed, oral contraceptives move through the digestive system, are altered by gut microorganisms, and are then absorbed across the wall of the small intestine • The hormones are first passed through the liver, which further metabolizes some of the molecules before they enter the general circulation • Thus, steroid composition is altered and the concentration is reduced through oral intake • Another method of delivery of steroid hormones is to implant a device containing steroids into the body, from which hormones can be released directly into the circulation • Subdermal ("under the skin") progestin implants have been used by women in various parts of the world as a long- lasting, reversible contraceptive measure and have been available since 1991 in the US • Under the currently available brand names Nexplanon or Implanon (approved by the FDA in 2006), a thin, flexible plastic rod containing the progestin etonogestrel is surgically inserted under the surface of the skin of the inner, upper forearm • The hormone is then released over the next three years • The progestin implant delivers a moderate dose of progestin and blocks ovulation in most cycles • A secondary mechanism of action is to increase the viscosity of cervical mucus, which prevents the movement of sperm into the uterus • The single- rod implant replaces Norplant, which was used by 1 million American women until it was taken off the market in 2002 • Norplant consisted of six match-stick- sized tubes containing the progestin levonorgestrel, which was then released in small amounts for up to five years • Norplant was withdrawn from the market primarily because the subdermal implants often proved difficult to remove • In fact, removal could result in pain, scarring, and even muscle or nerve damage- lawsuits were filed in this regard • Additionally, some women experienced side effects such as menstrual irregularities, dizziness, depression, moodiness, nausea, headache, acne, and weight gain • The newer subdermal progestins are easier and quicker to implant and to remove • Most women using Implanon/Nexplanon experience irregular or prolonged uterine bleeding, especially during the first 6-12 months of use • Other side effects may include amenorrhea, headaches, nausea, mood swings, slight weight gain, and either improvement or worsening of acne • Use of the implants may not be confidential as they might be visible under the skin • Contraceptive implants, however, have some distinct advantages • They are convenient, do not require taking a daily pill, and are among the most effective types of reversible birth control, with a failure rate of about 0.05% • Like other progestin -only contraceptives, the progestin implant can be used by women who are breast-feeding • After removal of a contraceptive implant, a woman is usually fertile again in a few months

Female Infertility • Age is an important factor in female infertility

- Women are most fertile in their early 20s - In the US, approximately 4.1% of women between the ages of 20 and 24 suffer from infertility; this increases to 5.5% at ages 25-29, 9.4% at ages 30-34, and 19.7% at ages 35-39 - The older a woman, the more difficult it is for her to conceive, even though she may be more emotionally and financially prepared to care for a child as she matures beyond her mid-20s

Preparation for Labor

About 2 or 3 weeks before labor, a woman could have a sensation of decreased abdominal distention produced by movement of the fetus down into the pelvic cavity - This is known as lightening- the baby has "dropped" - Lightening occurs about 2 weeks before birth in a woman having her first baby but may not occur until labor begins in her subsequent pregnancies - A woman literally breathes easier after lightening because of less pressure on her diaphragm - She may urinate more frequently because the fetus is now pressing on her bladder - A few hours to a week before labor begins, the part of the fetus that will exit first (usually the head) moves down into the pelvic girdle - engagement of the presenting part

a zygote with the genotype XO will develop into a female and have

turner syndrome and it is viable

menorrhagia or hypermenorrhea

is a condition representing heavy menstrual bleeding

identify the falsest statement

leptin doesnt seem to play any role in the development of puberty

in males which cells are primary target for LH and what is the effect on these cells

leydig cells and produce testosterone

what is the main function of prolactin in humans

production of milk breast milk production

which of the following occurs day 6-14 of the menstral cycle

proliferative phase

heterosexual to homosexual

0-6 0 complete heterosexual

the tyrosine kinase receptor has

1 membrane receptors domain

The Process of Pregnancy • Extraembryonic Membranes

- The inner cell mass produces three of the four extraembryonic membranes - The first of these to be formed is the yolk sac, which is an endoderm- lined membrane that surrounds the blastocoel; the blastocoel now is called the yolk sac cavity (Figures 10.3 and 10.4) - The yolk sac is not functional in humans, but remains as a vestige reflecting our evolution from ancestral reptiles that relied on stored yolk for embryonic nutrition - Most mammalian eggs have little or no yolk, and nutrients are instead transferred from maternal to embryonic circulation via the placenta - The human yolk sac degenerates early in development - Before it does, it supplies the embryo with blood cells - Another extraembryonic membrane formed from the inner cell mass, the amnion, then grows over the forming embryo (Fig.10.4) - The amniotic cavity becomes filled with amniotic fluid - The amnion is an important extraembryonic membrane throughout development - The fluid in this sac supports and protects the fetus against mechanical shock and supplies water and other materials to the fetus • The amount of amniotic fluid is about 5-10ml after eight weeks of development, about 250 ml at 20 weeks, and increases to a maximum of 1000- 1500ml by the 38th week of pregnancy • The amount of amniotic fluid then declines to 500- 1000 ml near the time of birth • Amniotic fluid is secreted and absorbed rapidly, at a maximum rate of about 300-600 ml per hour - The third membrane is the allantois, which forms as a small pouch at the posterior (tail) end of the embryo • Although it has important functions in waste storage and gas exchange in birds and reptiles, the human allantois is a vestigial sac not used for these functions • Primordial germ cells originating in the proximal epiblast appear at the base of the allantois before migrating to the developing gonads • The allantois briefly extends into the umbilical cord of the early embryo • Blood vessels formed in the allantoic tissue contribute to umbilical cord development - A fourth membrane, the chorion, is derived from the cytotrophoblast and surrounds the embryo after about one month of development; the chorion eventually fuses with the amnion (Fig. 10.4)

The Process of Pregnancy •Placenta

- The placenta is an organ vital to the developing fetus • Fetus receives important substances such as oxygen and glucose • Eliminates toxic substances such as carbon dioxide and other wastes - About the 14th day after fertilization, finger-like projections of the cytotrophoblast extend through the syncytiotrophoblast and toward the vascular uterine stroma • Projections are called chorionic villi because the trophoblast grows to surround the embryo and thus forms the chorion • The syncytiotrophoblast surrounding the chorionic villi secretes enzymes that dissolve the walls of small uterine blood vessels present in the stroma so that the mother's blood forms small pools (sinusoids) that actually bathe the villi • The human placenta is termed a hemochorial placenta - The mother's blood never mixes with that of the fetus • Chorionic villi contain small blood vessels fed by blood coming from the fetus via the umbilical arteries in the umbilical cord • Materials from the mother's blood, such as oxygen and glucose, then diffuse or are transported from the uterine sinusoids through the thin walls of the chorionic villi and into the fetal vessel within each villus • These materials travel to the fetus via the umbilical vein • Fetal waste products such as CO2 leave the fetal blood and diffuse into the mother's blood to be excreted • Placenta serves as a nutrient, respiratory, and excretory organ • Also secretes hormones that are vital to pregnancy - Molecules > about 500 molecular weight will not pass from the mother's blood into the fetal circulation • Too large to diffuse through the chorionic villi and into fetal blood vessels - Most protein hormones of the mother do not reach the fetus - this is important because maternal pituitary hormones could adversely alter fetal development - Some large proteins from the mother do reach the fetus near the end of pregnancy • Maternal antibodies, which are actively pumped into the fetal circulation by placental cells • Fetus is born with its mother's immunological protection against disease - Steroid hormones in the mother's blood are small enough to cross the placenta - most do not because they are degraded by placental enzymes - Other maternal hormones, such as thyroxine, can enter the fetus • Hypersecretion or hyposecretion of a woman's thyroid hormones during pregnancy can harm fetal development - Bacteria are too large to cross the placenta, but many harmful viruses, such as HIV, as well as drugs such as cocaine and alcohol, can cross the placenta - The placenta continues to grow, like an expanding disk, throughout pregnancy • At 4th week of pregnancy- placenta covers about 20% of the inner wall of the uterus • By week 20 it covers about half the uterine wall • At this time, the placenta weighs about 200g, and the fetus weighs 500g • At term, the placenta is a disk-like structure that weighs about 700g (about 1.5 lbs) and has a diameter of 20cm (8in) • Although the size of the term placenta varies among individuals, it is usually about one -sixth the weight of the term fetus - The placenta is an extremely vascular organ • Near the end of pregnancy, about 75 gal (285 l) of blood pass through the placenta daily; this is about 10% of the total blood flow in the mother • Although supporting the fetus, the placenta has a life of its own; if the fetus dies or is removed, the placenta continues to flourish - As the fetus and placenta grow, the stratum functionalis of the endometrium is transformed into the "decidua" of the pregnant uterus (Fig.10.6) - The maternal part of the placenta is the decidua basalis - The overgrowth of the endometrium during implantation (the deciduoma response) is now the decidua capsularis - The endometrium away from the fetus is the decidua parietalis - The fetus actually resides within the uterine wall, not in the uterine cavity - The umbilical cord connects the fetus with the placenta and is the lifeline of the fetus • It is derived from a structure connecting embryo and chorion, the body stalk • At birth, this cord is 0.3-1.0 in (1-2 cm) in diameter and 20-22 in (50-55 cm) long • It is covered by the amniotic membrane and contains two umbilical arteries (which carry deoxygenated fetal blood to the placenta) and one umbilical vein (which carries oxygenated blood back to the fetus) • Normally, arteries (vessels carrying blood away from the heart) contain oxygenated blood and veins (vessels carrying blood toward the heart) carry deoxygenated blood. • Vessels within the cord are cushioned by a gelatinous substance, Wharton's jelly

in the testes the first step in the process of meiosis is division of primary spermatocytes to produce

2 secondary sperm cells spermatocyes

meiosis of the -- cell results in

4 gametes in male and one gamete in females

which of the following enzymes is responsible for the conversion of testosteron to DHT

5-alpha reductase

in ovary of a newborn human female contains

500,000 folllicles

in the luteal phase granulosa cells are converted into

luteal cells

overian cycle is initiated by which of the following hormones

FSH

which pituitary hormone controls development of corpus luteum after ovulation

luteinizing hormone (LH)

identify the falsest statement regarding individals with conginetal adrenal hyperplasia

males cannot inherit this disorder they can

which of the following is not a function of testosterone

promotion of physical function and maturation of the spermatozoa

which of the following occurs during an erection

The parasympathetic nervous system dilates the arteries going into the penis.

the rate limiting enzyme in catecholine synthesis

Tyrosine Hydroxylase

endocrine changes during menopause include the folllowing except

adrenals drastically reduce androgen producting causing a decline in circulating

mature spermatozoa mature in human males

age 14-15

binding of a ligand is followed by by observable changes in the target cells that are charactersitic of

all of the above

sex drive in men depends on circulating levels of testerone which is influenced by

all of the above

identify the falsest statement regarding individuals with androgen insensitivity system

all of the statements are correct none of the above are false

the interstial cells produce

androgens

testicular descent under the control of 2 main hormones that

anti mullerian testosterone converted to DHT testosterone directly is incorrect

Sally is an avid jogger and she trains incessantly. She has slimmed down so that she is now underweight for her height and has very little fat tissue. You would expect Sally to

be amenorrheic

the function of IP3 produced by the activation of

bind and to open calcium channels

what is the difference in FSH and LH levels in infant boys and girls

boys- high LH girls- High FSH

small pear glands at the base of the penis that produce mucus like secretions

bulbourethral glands

erectile tissue that surrounds the urethra is called

corpus spongiosum

removal of ovaries in an adult woman has little or no effect on libido

correct

If the ovaries were removed from an otherwise healthy 20-year-old female, which of the following would not happen

decrease blood levels of LH increased blood levels of FSH will happen cessation of menstration will happen

at what stage of development GnRH begins to function

develops and begins in first trimester of fetla life

the fourth prenatal month

doesnt occur after birth occurs before birth idk wtf hes talking about tbh descent

the structure of the male reproductive tract sequence

epidiymis vas deferns ejeculatory duct urethra

which of the following results in feminized behaviors in males

estrogen and antiandrogens together

Menstration is triggered by a drop in the levels of

estrogen and pogesterone

identify the falsest statement in response to rising gonadotropin levels

estrone is produced primarly by follicles undergoing astrichia

the structure that transports the ovum to the uterus

fallopian tube

activation of the g protein by activates the cyclic AMP

false

estrogen and progesterone from corpus luteum exert a positive feedback effect in the pituitary to release LH

false

even after a womans cycle has ended and she is in true menopause FSH and LH

false

majority of breast cancer in women are due to an inheritance of inheritance of a gene mutation

false

many bacteria, fungi, and protozoa present in the vaginal environment always cause harmful infections

false

menstrual cycle begins with a surge of FSH and LH and onset of menses

false

ovaries is primary source of weak androgens such as

false

there is a dramatic increase in genetic after 25

false

testes is derived from

gondal medulla

what are the symptoms of PCOS (polycistic ovarian syndrome)

high circulating androgen levels causes acne, body hair growth, lack of ovulation, irregular or missing periods

limbic system includes

hippocampus, amygdala, hypothalamus

during menopause FSH and LH levels

increase due to lack of negative feedback

some pubertal males exhibit slight growth of mammary glands due to

increase in estrogen levels during puberty

How does Viagra work?

inhibit PDE to break down cGMP more cyclic gmp to be present

The role of the pituitary hormone FSH in males is to

initaite sperm production in the testes

explain what might happen to a man taking sympathetic nervous sysytem inhibitors to treat hypertension in terms of

it affects ability to orgasm - ejeculation problems will be impaired

what is the role of quasi complex in peptide hormone synthesis

it packages hormones which is then carried by enzymes for exocytosis and released by exocytosis

the peptide --- may play a role in positive feedback of estrogen on GnRH secretion

kisspeptin

hormone replacement therapy is often used to treat symptoms of menopause typically estrogen and progesterone are used rather than GnRH, FSH, and LH

lack of mature follicles so they cannot respond to GnRH, FSH, and LH. gonadotropin has no function bc no follicles to act on

in the follicular phase of ovarian cycle the ovary is

maturing the follicle

Uterus is derived from the

müllerian ducts

----- males exhibit abnormally high levels of FSH and LH in their blood suggesting testicular substances exert a

negative feedback on gonadotropins

indifferent gonads develop into testes under the influence of

none of the options

briefly describe the consequences of increased

offspring neurological disorder most harmless but more you have greater chance of having problems more chances of neurological disorders

rhythmic contractions of the uterus during female orgasm are probably brought about by the hormones

oxcytocin

which of the follwoing hormones has or have more defined function in females

oxyctocin and prolactin

certain characteristics that change in a predictable order during male puberty have been classified in 5 tanner stages

physical pubic hair penis testes hormone levels are not apart

what is the role of sustained high levels of estrogen in women in the feedback regulation of gonadotropin levels

positive feedback

which of the following occurs days 15-28 of the menstral cycle

secretion phase

what is the role of sox 9 gene in the development of male and female

sertoli cell development

these cells support and regulate spermatogenesis

sertoli cells

in males which cells are the primary targets of FSH what effect does the hormone have on these cells

sertoli cells and makes sperm, produce new androgen binding proteins

give an example of short loop negative feedback in the neuron control of reproduction

short loop = closed loop pituitary to hypothalamus GnRH causes production and release of gonadotropins then gonadotropins can go back to if high levels of gonadotropins they go back to inhibt GnRH

a boy who has not passed through puberty sustained an injury to his interior pituitary such that FSH is no longer released but LH is normal in this case after this individual grows to maturity one would expect that he would be

sterile

fertile or sterile

sterile because few degrees lower which allows for normal development of the sperm

hysterectomy

surgical removal of the uterus

what is the half life

time it takes for removal of half of hormone thru the blood

FSH stimulates estrogen synthesis by granulosa cells of tertiary follicles by inducing the production of aromatase

true

certain sequences of amino acids can facilitate binding of hormone response elements

true

early indication the germ cells of the have entered the female pathway

true

mitotic division in female germ cells are complete before birth

true

progesterone lowers female libido in comination birth control pills

true

sexual response can be elicited by applying electric in limbic system

true

single dominant tertiary follicle produces most of the estrogens circulating in the woman bloodstream

true

the enzyme mono oxidase serotonin dopamine and epinephrine

true

there seems to be an effect of the number of lifetime ovulations and timing of menopause

true

how does delta 5 pathway differ from delta 4 pathway in terms of steriod hormone production

two pathways that make androstenedione at the end of the pathway that can be converted to testosterone and then testosterone can be converted to estrogens delta 4 makes progesterone and delta 5 does not make progesterone goes thru DHEA

embryo with urethral fold urethral groove early stage embryo would be

under 7 weeks old

identify the falsest statment about weak androgens

when these androgens arrive at atarget tissue they are converted to testosterone by 5-alpha-reductase

male reproductive structures from

wolffian ducts

the dax 1 gene is presented on the

x chromosome - short chromosome

chromosomal aberrations

• Errors of meiosis or fertilization can produce embryos with chromosomal aberrations - More than 90% of these embryos are aborted spontaneously, usually within the first trimester - In fact, more than 50% of embryos or fetuses that are aborted spontaneously have chromosomal abnormalities - A few fetuses with chromosomal defects, however, are born; about one out of every 100 newborns has such a defect - It must be emphasized that some of these disorders are not inherited in the strictest sense because the genes of the parents do not govern their occurrence - One kind of chromosomal aberration occurs when fertilization fails to activate the second meiotic division in the ovum - Thus, there is no egg pronucleus, and the embryo develops with only one set of chromosomes (haploid) and genes of the male only • This process of embryonic formation is termed androgenesis - A similar situation occurs when the ovum pronucleus develops normally but the sperm pronucleus does not form • In this case, called gynogenesis, the embryo also is haploid but has only the female's genes - Both of these conditions are lethal after only a few cell divisions in the embryo • Some embryos may develop with triploid cells (3N) that have 69 chromosomes (three complete sets) - Triploidy can occur in at least three ways 1) The sperm penetrating the ovum may be the product of a failure of reduction division during meiosis in the testis, and thus it has 46 instead of the normal 23 chromosomes - When this sperm fertilizes a haploid ovum, a triploid embryo develops 2) Even though mechanisms to prevent polyspermy are present, these mechanisms are not failsafe - Two haploid sperm can penetrate a single ovum (polyspermy) and both of their pronuclei then fuse with the haploid ovum pronucleus 3) Reduction division (meiosis) may not have occurred in the oocyte - The resultant diploid female pronucleus then fuses with a haploid sperm pronucleus to produce a triploid zygote - The excess dosage of genes in triploid embryos tends to be less destructive than when there are too few genes, as in androgenesis or gynogenesis - Most triploid embryos develop to about the third month of pregnancy before aborting spontaneously - The very few triploid fetuses that survive to term are malformed and are stillborn or die soon after birth - Less than 1% of all human embryos are triploid • Another error in fertilization results in embryos with either 47 or 45 chromosomes in their cells - These conditions are collectively called aneuploidy - This happens when there is aberrant chromosome movement during the first or second meiotic division in the testis or ovary or in the first cleavage division of the zygote • ie., a pair of chromosomes fails to separate during division, with both members going to one daughter cell (nondisjunction) • The resultant cell has 47 chromosomes, and the cell coming up short has only 45 - The aneuploid condition can be either monosomic (45 chromosomes) or trisomic (47 chromosomes) - Most monosomic embryos abort spontaneously early in their development - An exception, however, is when monosomy for a sex chromosome occurs • Each cell has only a single sex chromosome, either an X or a Y - Embryos with only a Y chromosome abort, as genes on the large X chromosome are necessary for life - A few embryos with one X (XO condition; Turner syndrome) are born as sterile females with short stature and male physical characteristics.

Twin Pregnancies

• Dizygotic (fraternal) twins develop from two separate zygotes - The two embryos usually implant separately, which results in two separate placentas and amnions (Fig.10.7) • In some cases, the embryos implant close to each other, which results in a common fused placenta and separate amnions • Monozygotic (identical) twins result from the separation of a single inner cell mass into two - The two embryos share a common placenta but each is enclosed in its own amniotic sac (Fig.10.8) - In some cases splitting of the early morula produces monozygotic twins with separate amnions and chorions and separate or fused placentas • In these cases, it is difficult to differentiate these monozygotic twins from dizygotic twins based on extraembryonic membranes alone

Vaginal Ring Hormone Delivery

• A plastic ring containing low- dose estrogen and progestin that is placed within the vagina - Marketed under the brand name NuvaRing • Hormones released steadily from the ring are transported across the vaginal epithelium and enter the bloodstream • The soft, flexible ring is about two inches in diameter. On the first day of the cycle the woman places the ring in the vagina, where it remains for three weeks • The exact placement is not critical, but generally it is placed high in the vaginal canal near the cervix • It is left in place for three weeks and then removed for a ring- free week during which withdrawal bleeding occurs • Most users can wear the ring comfortably or not feel it at all, even during intercourse • It may be removed for a maximum of three hours at a time without losing effectiveness - The vaginal ring may occasionally be disrupted during sex or a bowel movement, and can be checked to make sure that it remains in place

Miscarriage

• At least half of zygotes and preembryos undergo miscarriage (spontaneous abortion) before or right after implantation - In these cases the woman is not aware of being pregnant - This occurs because of genetic or chromosomal damage to the cells, immune responses, improper hormonal priming of the uterus, or exposure to drugs or pollutants - After pregnancy is established, chromosomal or genetic errors account for 50% of miscarriages - About 15% of established pregnancies terminate by miscarriage, usually in the first trimester - Other factors that can induce spontaneous abortion after pregnancy is established include exposure to teratogens or mutagens, maternal stress, severe undernutrition, vitamin deficiencies or excessive amounts of vitamins (especially vitamin A), thyroid and kidney disorders, diabetes, and uterine abnormalities - The rate of miscarriage is also higher in older women - When pelvic infection causes spontaneous abortion, it is called a septic abortion

contraception introduction

• An ideal contraceptive would be 100% effective with no side effects, easy to use, reversible, effective for men and women, and free! • Many options are available - Current methods of contraception, including their usage, advantages and disadvantages, mechanisms of action, effectiveness, and major and minor adverse side effects • Hormonal methods override a woman's natural endocrine cycle to inhibit ovulation • Surgical sterilization and barrier contraception block the passage of gametes through the male or female reproductive tracts • Some contraceptive methods may also prevent the transport of a developing preembryo through the oviduct or implantation of a preembryo in the uterus - In the US today, almost all women in their childbearing years (between the ages of 15 and 44) who have ever had intercourse have used some form of contraception (Table 13.1) - At a given time, only 62% of sexually experienced women of childbearing age report currently using a contraceptive method - The combination birth control pill is the most popular contraceptive method overall (used by 17.3% of women) - Sterilization by tubal ligation is used by almost as many women (16.7%) - The male condom is the third most commonly used form of contraception (10%), followed by male sterilization (6.1%) - There are differences in contraceptive use among people of different ages, educational levels, marital status, race, and ethnicity - Sterilization (female and male) is the most used method among married couples, whereas the combination birth control pill is the method of choice of never-married women - Use of the birth control pill is greater among younger women and those with a higher educational level • The birth control pill is much more commonly used among white women (21%) than among black or Hispanic women (11%) • As a woman ages, she is less likely to take the pill and more likely to use sterilization as a contraceptive • A common pattern is for a US woman to use a condom when first becoming sexually active, the pill to delay the first pregnancy, and surgical sterilization when she has completed her family • 7.3% of US women are not using contraceptives despite wishing to avoid pregnancy, and therefore are at high risk of an unwanted pregnancy - About 4 million births occur each year in the United States • One-third of these are to unmarried women • Approximately 55% of these births to unmarried women result from unplanned or unwanted pregnancies • Even in married US women, about 30% of pregnancies resulting in live births were unintended • The rates of unplanned pregnancies and abortions in the US are the highest in the industrialized world • Fully half of all women in the US will have had an unplanned pregnancy between the ages of 15 and 44, despite the fact that nine out of 10 women at risk for an unwanted pregnancy report that they use contraception • Even when contraceptives are used, they are often used inconsistently or incorrectly, and about one-half of the unintended pregnancies in the US are due to misuse of contraceptives • In contrast, women who use contraception consistently and correctly account for only 5% of unplanned pregnancies • Modern contraceptives work well when used correctly

Completion of the Second Meiotic Division

• The ovulated egg is arrested in the second meiotic division and still has a duplicated set of chromosomes - Before merging with sperm DNA, the egg must complete its second meiotic division and jettison half of its chromosomes - At fertilization, the rise in free calcium activates the egg nucleus to complete meiosis, and a second polar body is produced, removing the extra set of chromosomes from the egg - The second polar body can often be seen in the perivitelline space before it degenerates (Fig. 9.6)

Sperm Hitch Hikers

• The sperm head contains a protein, fertilin-ß, on its surface - After the sperm penetrates the zona pellucida, the tip of its head approaches the vitelline membrane - The head turns laterally so that one side of the sperm head attaches to the vitelline membrane - Fertilin-β appears to mediate this lateral attachment - If this protein is absent, fertilization does not occur because sperm- oocyte binding is inhibited - Fertilin-deficient sperm also have a reduced ability to bind to the zona - Our understanding of the normal action of fertilin is still evolving • When the sperm penetrates the egg, waves of stored calcium ions are released in the egg cytoplasm - This sudden increase in calcium triggers egg activation (cortical granule release and reinitiation of meiosis). Scientists have long speculated that the trigger for calcium release is carried by the sperm - Researchers have found that the sea urchin sperm head contains an enzyme that can synthesize nitric oxide - This gas is injected into the egg at fertilization and can set off a calcium surge - It remains to be seen if a similar mechanism operates in humans - Study of human eggs has revealed that phospholipase C is carried by sperm into the egg. It can also cause the waves of calcium release and egg activation • Ribonucleic acid (RNA) is produced when cells read the DNA sequences coded by genes and transcribe these messages - During the later stages of spermatogenesis, sperm DNA becomes tightly compressed and gene expression ceases - However, scientists have found that sperm RNA is still present in the mature sperm even at fertilization - This is especially surprising because the sperm cytoplasm is virtually gone - Sperm cells contain an amazing repertoire of RNAs - It turns out that about 3000 of the 20,000-25,000 human genes are represented by sperm RNA - Some of the mRNAs represent known genes, others are unknown, and some of the RNAs do not code for proteins - Many types of mRNAs are found in the sperm cell nucleus • Most of these 3000 transcripts are probably leftover RNA instructions for building the sperm cell during the process of spermatogenesis - However, scientists have identified six RNAs present in the spermatozoa but not in the unfertilized egg - Are these transcripts carried into the egg at fertilization? • If the sperm delivers RNAs into the egg at fertilization, one would expect to find these RNA sequences in the sperm and in the zygote, but not in the unfertilized egg • Using cDNA probes, they found two sperm RNA sequences that are delivered to the egg at fertilization - What happens to RNAs delivered by the sperm? • Possibly they are simply destroyed by the egg cytoplasm • However, it is also possible that these RNAs act as instructions for early embryonic development and that they are needed to launch the developmental program of the zygote • In fact, one of the mRNA transcripts delivered to the egg codes for clusterin, which has been implicated in cell - cell interactions, membrane recycling, and regulation of apoptosis (programmed cell death), processes central to embryonic development - Preliminary evidence shows that the sperm of some infertile men lack some of the RNAs carried by sperm of fertile men - It is thought that a treatment that lowers or eliminates the RNAs from the sperm of fertile men may render them infertile, thus providing a potential male contraceptive method - Some scientists use the absence of male RNAs as a possible explanation of why embryonic development is so poor in most cases of cloning and in all cases of human parthenogenesis; neither process involves sperm - However, others cite the occasional success of cloning to argue against an important role for sperm RNAs

Sperm Passage through the Zona Pellucida

• The zona pellucida is an extracellular matrix composed of three glycoproteins: ZP1, ZP2, and ZP3 - Receptors on the sperm plasma membrane attach to ZP3 - Binding to ZP3 allows the sperm to adhere to the zona pellucida - a critical step in fertilization - Triggers the sperm head to undergo the acrosome reaction - An influx of calcium and a rise in pH and cAMP levels within the sperm head cause exocytosis of the acrosomal vesicle - Exocytosis occurs when the plasma membrane of the sperm fuses with the outer acrosomal membrane, forming many small openings to the acrosome - Contents of the acrosome, which are hydrolytic enzymes, spill out and degrade the zona pellucida near the sperm head - This forms a tunnel in the zona, through which the sperm begins to move (Fig. 9.5) - Degradation of the sperm plasma membrane during the acrosome reaction causes the loss of ZP3 receptors - The inner acrosomal membrane is exposed, and it appears to have receptors for another zona pellucida glycoprotein called ZP2 - This ZP2 binding maintains the contact between egg and sperm - The sperm tail continues to beat vigorously, helping the sperm penetrate through the zona pellucida and make contact with the plasma membrane of the egg - Once the sperm has penetrated the zona pellucida, it moves through a narrow, oblique path into the perivitelline space (the area between the zona pellucida and the vitelline membrane, Fig. 9.4) - Penetration of the human zona pellucida by a sperm takes less than 10 min under experimental conditions

pregnancy introduction

• The zygote divides mitotically to form two blastomeres - These cells divide to produce four smaller blastomeres - It takes only about 42 such sets of mitotic cell divisions to produce a newborn baby • The number of cells in the developing human increases exponentially - Not only proliferation but also cell differentiation takes place so that cells become disparate in form and function: some become liver cells, nerve cells, or muscle cells ... - The zygote gives rise to the embryonic part of the placenta as well as to the embryo itself - We'll cover the process of pregnancy, or gestation, during which the mother supports a developing human to a stage at which it can exist in the outside world

Pregnancy

•It takes about 38 weeks for a developing human to grow from a zygote about the size of a tiny dot to a birth weight of 7.0-7.5 lbs or so - Until it has implanted in the uterus by about 10 days after fertilization, the developing organism is a preimplantation embryo, or preembryo, and this time span is often termed the embryogenic stage - The developing organism is called an embryo during weeks three through eight of development; after week eight, it is termed a fetus - The term conceptus is also used to refer to the products of conception (the embryo or fetus plus extraembryonic membranes) - In most textbooks and in legal rulings about induced abortion, pregnancy begins at fertilization -the definition used also in this book - Pregnancy on average lasts 38 weeks (8.75 months, or 266 days), with trimesters of approximately three months each - In most of the medical profession, however, due dates for birth are calculated from day one of the last menstrual period, and so are trimesters - This is because the timing of fertilization is difficult to know, whereas women can usually remember the first day of their last menstrual period - Using this calculation, pregnancy lasts 40 weeks, or about 9.2 months (280 days on average), although the first two weeks of "pregnancy" occur before fertilization even takes place - Finally, most of the general public feels that pregnancy begins "when you are pregnant," i.e. two weeks or so after conception, after your "missed menses," or when there is a positive pregnancy test or other signs of pregnancy • In this case, one would begin trimesters with a positive pregnancy test - From the mother's perspective, pregnancy is perhaps best defined as beginning at implantation