ENDO/REPRO Exam 2: Reproduction

1. What is the primary gene that determines sex? Which sex has it and which sex lacks it? 2. Understand the manifestations of 5-alpha-reductase insufficiency and Androgen receptor insensitivity. "Very important slide" Female Physiology Before Pregnancy and Female Hormones

SRY gene - Causes male differentiation - It's the sex-determining region of the Y-chromosome. SRY is the Sex-determining region of Y chromosome (Protein product is Testis determining factor, TDF) The SRY Gene becomes activated in male fetuses (encodes a transcription factor with many gene targets that direct male sex differentiation) Females- no SRY, hence, default development Fetal Sertoli cells are the first cells to differentiate under control by SRY; make AMH aka MIS or MIF to cause mullerian regression (regression of female development). Fetal Leydig cells make androgens for masculinization of male fetuses.

List the common risk factors for development of breast cancer Breast Pathology

See Image "Note that at least 4 risk factors are directly related to hormones." Radiation exposure is a big risk Genetic: BRCA1 or BRCA2 - Autosomal dominant - Can be inherited from mother or father

If an ultrasound shows plenty of antral (secondary) follicles, what does this indicate about the woman's fertility? Female Microanatomy/Reproductive Microanatomy PI

She is fertile. If there are none or not many, probably infertile. Antral/Secondary follicles develop from oocytes as the first step of follicle production.

36 yo G1 P0 presents for her first prenatal visit at 8 weeks since last menstrual period. She asks about prenatal testing options for Down syndrome and other chromosomal abnormalities. This patient has a 1 in 87 risk for aneuploidy (at this point in pregnancy). Concerning prenatal tests for chromosomal abnormalities, what would be the best test for each scenario?: 1. She says "It's not important when we find out, we just want to know for sure." What would you offer? 2. She says "I want to know as soon as possible, but I don't want to have any unnecessary risk." What would you offer? Preconception and Prenatal Genetics

"This is a common clinical scenario" 1. If you want to know FOR SURE, you should get a diagnostic test. Amniocentesis is the best way to go. Most information. Would do this at 15 weeks, so she woud have to wait. But that's okay because she doesn't care when they find out. 2. If you want to know soon and want a test with NO risk to the fetus, you would need a non-invasive test (prenatal screening test). The best one would be NIPT (non-invasive prenatal testing).

Endometrial 'window of receptivity': - On what days after ovulation is the uterus ready to accept the embryo? - This is associated with a surge in what hormone? - The process of making the endometrium ready for implantation is driven by what hormone, which causes the uterus to become more secretory for a potential embryo? Female Reproductive Physiology: Pregnancy and Lactation

- Days 6 to 10 after ovulation (LH surge) - Progesterone-driven process -- leading to differentiative changes in endometrium; endometrial glands become highly secretory. >> Progesterone is the hormone of pregnancy 'Developmental synchrony' of endometrium and blastocyst is important; an 'out-of-phase' uterus (non-receptive; not properly prepared) may lead to failed implantation.

++++++++++++++++++++++++++++++ Physiological Changes in the Mother during Pregnancy: - Cardio: What happens to SVR, pulmonary vascular resistance, HR, and CO? - Coagulability - Respiratory Rate - Pituitary hormone secretions Female Reproductive Physiology: Pregnancy and Lactation

- Increase in Cardiac Output and Heart Rate - May become Anemic (due to increase in blood volume to support growing fetus; begins around 24 weeks and peak at close to parturition) - Hypercoagulability ( to decrease blood loss at delivery) - Hyperventilation (to eliminate fetal carbon dioxide) Pituitary (Endocrine) - High level sex steroids suppress hypothalamic-pituitary-ovarian axis, preventing ovulation (negative feedback) - Estrogens (from ovary) stimulate prolactin release, beginning in first trimester of pregnancy

Masculinization of the germ cells: - ___ cells secrete testosterone, which can be converted to dihydrotestosterone (DHT), both of which are key in masculinizing the fetus. - What gene promotes male gonad formation? - Mesonephric ducts are present in ___. - Paramesonephric ducts are present in males or females? - Anti-Mullerian Hormone: Secreted by ___ cells. Has what role in male development? Embryonic Development of Gonads and Duct Systems

- Leydig Cells: Secrete Testosterone: converted by 5 alpha reductase to Dihydrotestosterone (DHT). Each has separate roles in masculinization, binding specific receptors. They will masculinize the entire body, including the brain. • Interstitial cells of Leydig (from mesenchyme) produce Testosterone which then influences "development of the genital ducts" -- 5-alpha-reductase => DHT => external genitalia. - Sertoli cells (male cells) secrete anti-mullerian hormone, which gets rid of all the female sexual parts in a developing male. So we're all females at first. - Y-chromosome transcribes SRY gene, which induces testicle formation. > Mesonephric ducts are present in Males. > Paramesonephric ducts are present in Females. - Before sex differentiation, both are present. Eventually, the unnecessary one will go away. - In males, the paramesonephric ducts degenerate from anti-mullerian hormone. - In females, the mesonephric ducts degenerate from lack of SRY.

Inflammatory Carcinoma of the breast: - Clinical features / presentation - What stage of cancer? - What two populations are at greatest risk? - Histological pattern Breast Pathology

- Orange peel skin: Skin of breast becomes very thick and red. - Dermal lymphatic invasion - Inflammatory carcinoma (clinical impression) is always considered stage T4 (locally advanced breast cancer) - African American and obese women are at greater risk - Histology: Fried-Egg appearance

Which phase of the menstrual cycle is it if a uterine biopsy shows: - Mitotic figures - Glycogen droplets beneath nuclei Female Microanatomy/Reproductive Microanatomy PI

- Proliferative phase: mitotic figures - Secretory phase (OVULATION): glycogen droplets

Human Chorionic Gonadotropin (hCG): - Produced where? - It reaches a measurable amount around day ___ of pregnancy, and can thus be measured for what major purpose? - Function during pregnancy is to maintain the ___, which maintains production of what two hormones during the first 8-10 weeks of pregnancy. Female Reproductive Physiology: Pregnancy and Lactation

- Synthesized by the placental trophoblast (peaks ~45-90 days after conception) - Measurable in maternal blood by days 7-8 post-fertilization and 2 weeks post-fertilization in urine (hence, used as basis of pregnancy test) - hCG maintains corpus luteum's synthesis of progesterone and estrogen

Stages of Breast Cancer: What is meant by each stage? - Tis - T1 - T2 - T3 - T4 - N__ Which two are considered "locally advanced"? Breast Pathology

- Tis: carcinoma in-situ (intraductal carcinoma) - T1: tumor less than 2 cm in greatest dimension (divided in T1a-T1c) - T2: tumor more than 2 cm but no more than 5 cm in greatest dimension - T3: tumor more than 5 cm in greatest dimension - T4: tumor of any size with direct extension to the chest wall or the skin (chest wall includes ribs, intercostal muscle, and exterior muscle but not the pectoral muscle) - N__ means it has metastasized to lymph nodes. N1, N2, N3, N4

Summary of Genital Development in Males vs. Females: - Mesonephric vs. Paramesonephric ducts - What does each of those turn into? - Main gene responsible for prenatal sexual development in males? - Urogenital sinus develops into ___ in females. Embryonic Development of Gonads and Duct Systems

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That big chart you need to know for Ovarian/Endometrial Cycles: - How pituitary hormone levels (LH and FSH) change - How the Follicles change - How ovarian hormones (estrogen, progesterone, inhibin) change - How the thickness of the endometrial/uterine lining changes Female Microanatomy/Reproductive Microanatomy PI

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What are the major roles of Progesterone and Estrogen during pregnancy? Female Reproductive Physiology: Pregnancy and Lactation

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1. A 25-year-old female patient with a history of pelvic inflammatory disease (PID) presents for preconception counseling. She heard from a friend that she is at higher risk for an ectopic pregnancy due to her history of PID, and she is curious about where fertilization and implantation usually take place. You tell her that fertilization normally occurs in which of the following anatomic locations? A. Ampulla of the fallopian tube B. Infundibulum of the fallopian tube C. Isthmus of the fallopian tube D. Isthmus of the uterus E. Vagina 2. A woman tests positive for pregnancy. In order for the pregnancy to proceed uneventfully, which of the following must occur? a. The corpus luteum must secrete progesterone to sustain the endometrium b. The pituitary must secrete hCG to maintain the corpus luteum c. The pituitary must secrete prolactin to sustain the placenta d. The placenta must secrete FSH to maintain ovarian function e. The placenta must secrete LH to maintain ovarian function 3. Judging by her last menstrual period, a 25-year-old women is in her tenth week of pregnancy. She complains that she has had minor vaginal bleeding for a couple of weeks. Physical examination reveals her fundal height to be above the level of the umbilicus. Which of the following hormones would be markedly elevated in this condition? a. 5-Hydroxyindolacetic acid b. Alpha fetoprotein c. Androgens d. hCG e. Estrogen 4. Placental secretion of progesterone stimulates: a) preparation of the mammary glands for lactation b) contraction of uterine muscles c) development of the female secondary sex characteristics d) pituitary oxytocin secretion Female Reproductive Physiology: Pregnancy and Lactation

1. A. Ampulla of the fallopian tube Fertilization normally occurs in the ampulla of the fallopian tube. Less commonly, it occurs in the infundibulum of the fallopian tube (Choice B), which is the funnel-shaped termination formed of fimbriae. After fertilization, the ovum remains in the fallopian tube for approximately 72 hours before being swept down the fallopian tube by cilia into the uterine cavity, where it implants. PID is a risk factor for ectopic pregnancy, as it can lead to tubal scarring or decreased peristalsis which, in turn, can lead to abnormal implantation outside the uterine cavity. Fertilization does not normally occur in the isthmus of the fallopian tube (Choice C), isthmus of the uterus (Choice D), or the vagina (Choice E). 2. a. The corpus luteum must secrete progesterone to sustain the endometrium Continuous secretion of progesterone by the corpus luteum is essential for development of the fetus. During the first trimester, placental production of hCG sustains the corpus luteum and ensures continued progesterone secretion. By the second trimester, progesterone production by the placenta increases to levels sufficient to sustain fetal growth and development. 3. d. hCG This individual likely has hydatiform mole. A molar pregnancy is often accompanied by vaginal bleeding, a larger uterus than normal for gestational age, and markedly elevated hCG levels. It characteristically becomes symptomatic in the early months of pregnancy. AFP is found to be elevated in many yolk sac tumors. Estrogen levels are elevated in granulose-theca cell tumors, and androgen levels are elevated in Leydig cell tumors. 5-HIAA is a marker for carcinoid tumors. 4. a) preparation of the mammary glands for lactation - One of progesterone's many functions.

++++++++++++++++++++++++ Menstrual Phase of the Endometrial Cycle: 1. Days __ to __ 2. Corresponds to which phase of the Ovarian Cycle? 3. Key event 4. Hormones: The drop in ___ and ___ allows ___ to surge and induce growth of new follicles. Female Microanatomy/Reproductive Microanatomy PI

1. Days 1-4 2. Ovarian Cycle Phase: Follicular Phase 3. Key event: Functional layer of endometrium is sloughed off. This is when bleeding occurs (period). 4. There is a drop in progesterone and estrogen due to the death of the Corpus Luteum (which secretes those) from the previous cycle. This allows FSH to be secreted and starts the stimulation of the next crop of follicles. Thus, this sign is considered the start of the menstrual cycle. - It's the period after the death of the corpus luteum in the previous cycle, and thus there is a drop in serum progesterone and estrogen. Since those inhibit FSH, lack of them results in FSH surge. - Follicles develop thanks to FSH, LH, and androgens from theca cells. But FSH is the main hormone involved.

++++++++++++++++++++++++ Proliferative Phase of the Endometrial Cycle: 1. Days __ to __ 2. Corresponds to which phase of the Ovarian Cycle? 3. Key event 4. Hormones: Induced and controlled by rising levels of ___. 5. What major event marks the end of this phase and the beginning of the Secretory Phase? Female Microanatomy/Reproductive Microanatomy PI

1. Days 5-14; It's the most variable period 2. Ovarian Cycle Phase: Follicular Phase 3. Key event: Proliferation of new functional layer. Basal layer grows up to form the new functional layer. Hence, "proliferative" phase. 4. Estrogen is rising in this stage - Consistent with follicular phase of ovarian cycle. - Word Document: If you know what hormones are rising during this phase, you know how the ovarian hormones affect the uterine endometrium. Recall that estrogen from the developing follicles stimulates proliferation of the endometrial gland. So, estrogen is rising during this phase and, appropriately, this phase is called the proliferative stage of the uterine cycle. 5. The end of this phase is marked by the beginning of Ovulation, in which the ovum is released from the ovary. This marks the beginning of the Secretory Phase.

Functions of the two types of cells found in oviduct mucosa: 1. Peg Cells 2. Ciliated cells Female Microanatomy/Reproductive Microanatomy PI

1. Peg cells: secretory - Nourish oocyte - Sperm capacitation (not needed in in vitro fertilization, however) - Inhibit growth of microorganisms (protective) - Fluid aids in transport 2. Ciliated cells: transport - Move fluid with oocyte or embryo towards the uterus

++++++++++ Popular Topic on Boards ++++++++++ Name the embryologic origin of each: 1. Becomes the erectile tissues in males and females: penis (glans penis, corpus cavernosum, and corpus spongiosum) in males; clitoris and vestibular bulbs in females. 2. Becomes the reproductive secretory glands: bulbourethral glands and prostate gland in males; greater vestibular glands and urethral/paraurethral glands in females. 3. Becomes the ventral shaft of the penis in males. Becomes the labia minora in females. 4. Becomes the scotum in males. Becomes the labia majora in females. Embryonic Development of Gonads and Duct Systems

1. Genital Tubercle (erectile Tissue) 2. Urogenital Sinus (secretions) 3. Urethral folds 4. Genital swelling

++++++++++++++++++ Determine the subtype of invasive breast cancer: 1. Small uniform round or oval nuclei diffusely infiltrating the stroma Malignant cells align in a single file pattern Negative for E-cadherin (adhesion protein) Majority are positive for the Estrogen receptor 2. Orange peel skin African American and obese women are at greater risk. Skin becomes very thick, and is red Very poor prognosis Breast Pathology

1. Invasive Lobular Carcinoma - Decent prognosis 2. Inflammatory Carcinoma - Skin becomes very thick, and is red. Both of those suggest inflammatory carcinoma. - Very poor prognosis - Always T4 stage -- locally advanced breast cancer

Defects in the development of the Uterus and Vagina - Name each defect described: 1. Incomplete fusion of the upper paramesonephric ducts along the midline (but normal sinovaginal bulb formation) 2. Sinovaginal bulbs fail to fuse 3. Sinovaginal bulbs fail to develop at all Embryonic Development of Gonads and Duct Systems

1. Uterus bicornis (double uterus) - Wikipedia: upper portion of the paramesonephric ducts don't fuse, but the distal portion that develops into the lower uterine segment, cervix, and upper vagina fuses normally. 2. Double vagina 3. Vaginal atresia Wikipedia: The sinovaginal bulb is a transitional structure in the development of female genitalia, and is one of a pair of endodermal outgrowths of the urogenital sinus, which later fuse to form the lower part of the vagina.

++++++++++++++++++++++++ Secretory Phase of the Endometrial Cycle: 1. Days __ to __ 2. Corresponds to which phase of the Ovarian Cycle? 3. The beginning of the secretory phase is marked by what major event? 4. Hormones: What hormone is high during this phase? Why? 5. The end of this phase is marked by what major event? 6. What happens in the endometrium during this phase? Female Microanatomy/Reproductive Microanatomy PI

1. Last 14 days (2 weeks) of cycle, usually days 15-28. Ovulation occurs during this phase. 2. Ovarian Cycle Phase: Luteal Phase - Other two are in the follicular phase of the ovarian cycle. 3. Progesterone surges during this phase, as the corpus luteum is intact and secreting it. 4. Beginning is marked by start of ovulation. 5. End is marked by menstruation, which is the beginning of the new cycle. Corpus luteum sheds. 6. Endometrium is forming new glands, which can nourish the potential embryo. Basically preparing for pregnancy. If that doesn't happen, mestruation occurs. - Progesterone thus turns the endometrial cells from proliferating cells to secretory cells, which are ready to support the implanting embryo. Thus, this phase of the uterine cycle is called the Secretory phase.

Partuition (childbirth) -- What: 1. Stimulates contractions; also cause cervical softening, dilatation, and thinning. 2. Increases at the end of pregnancy, causing increases in myometrial PG and oxytocin receptor numbers 3. Stimulates gap junction formation in myometrium to facilitate coordinated contractions. 4. Increases PG synthesis and secretion, stimulates contractions in myometrial cells and promotes dilation of cervix. Female Reproductive Physiology: Pregnancy and Lactation

1. Mainly Prostaglandins, also estrogen 2. Estrogen 3. Estrogen 4. Oxytocin

NIPT (Non-Invasive Prenatal Testing): (Prenatal Screening Test) 1. Measures what in the mother's blood? 2. Provides what information about the fetus? 3. It is ONLY recommended under what condition? Preconception and Prenatal Genetics

1. Measures Cell-Free DNA 2. Detects chromosomal abnormalities: trisomies 21, 18, and 13, monosomy X, and other sex chromosome anomalies. All it can tell you is if there is an abnormal amount of a particular chromosome. Cannot diagnose from this. Does not test for neural tube defects (NTDs). So it tells you about fetal DNA. Is it normal or are there some abnormalities? Only available after 9-10 weeks of gestation. Before then, there's just not enough fetal DNA to get an accurate measurement. Ex: If the test comes back with more than expected amounts of chromosome 21, you would be suspicious of Trisomy 21 (Down's). That's the gist of this test. 3. It is ONLY recommended for mothers who are at "HIGH RISK" for having a child with a chrom. abnormality (i.e., older age, were positive with other screening test, etc). Whole slide on this. "Do not yet recommend for low risk women and multiples." Image: "NIPD" is x'd out because that term is not used anymore. The other three, NIPT, NIPS, and cffDNA are synonymous (FYI). Also, FYI, NON-invasive like all screening tests -- no tissue sample is taken.

++++++++++++++ KNOW THIS +++++++++++++++ Endometrial/Uterine phases - Mentrual, Proliferative, and Secretory: 1. What key event happens during each? 2. What days of the cycle are in each? 3. FSH is high in which phase? 4. Estrogen rises in and controls which phase? 5. Progesterone from the corpeus luteum rises in and controls which phase? 6. Which 2 phases corresupond to the Follicular phase of the ovarian cycle? 7. Which one phase correlates to the Luteal phase of the ovarian cycle? Female Microanatomy/Reproductive Microanatomy PI

1. Menstrual Phase: - Days 1-4 - Key event: Endometrium functional layer sloughed off. Period / Bleeding occurs. - FSH is high since progesterone and estrogen are low (due to death of corpus luteum from previous cycle). FSH, along with LH and androgens, promote growth of new endometrial follicles. - Corresponds to follicular phase ovarian cycle 2. Proliferative Phase: - Days 5-14; most variable period - Influenced by rising estrogen - Basal layer grows up to form a new Functionalis layer. - Corresponds to follicular phase of ovarian cycle 3. Secretory Phase: - Days 15-28 (or last 14-16 days / 2 weeks of cycle) - Influenced by Progesterone from Corpus Luteum. - Glands develop to nourish embryo - Corresponds to luteal phase of ovarian cycle

Chorionic Villus Sampling (CVS): (Prenatal Diagnostic Test) 1. What is it and How is it performed? 2. What information does it tell you? 3. Risk? 4. Can only test for ___, not ___. 5. Should be performed only between ___ to ___ weeks of gestation. Preconception and Prenatal Genetics

1. Placental biopsy. Tissue sample obtained, usually through abdomen. 2. Then tissue sent for chromosomal analysis to check for chromosomal abnormalities. 3. Slight risk of hurting fetus, even killing it or causing limb abnormalities. But usually pretty safe. Don't want to do it too late in pregnanacy. 4. Limitation: Can only test for chromosomal abnormalities, not for alpha-feroprotein (AFP) (neural tube defects). Only at risk if done before 9 weeks, so DON'T perform until 10th week of gestation. 5. Should be performed between 10-13 weeks of gestation. No earlier than 10 weeks!

Amniocentesis: (Prenatal Diagnostic Test) 1. What is it and How is it performed? 2. What all can be determined from testing amniotic fluid? 3. Can be done anytime after __ weeks of gestation. Preconception and Prenatal Genetics

1. Removal of amniotic fluid (and fetal cells) from the amniotic cavity around the fetus. 2. Chromosomal abnormalities PLUS Alpha-feroprotein (AFP) and acetyl cholinesterase testing can be performed on the fluid, which can detect the majority of open neural tube defects. CVD can't detect NTDs. 3. Can be done anytime after 15 weeks

++++++++++++++++++++ 1. When is an oocyte ready to be fertilized? This coincides with what histological finding? 2. When is a second polar body formed?

1. The oocyte is ready to be fertilized after it is arrested in Metaphase of Meiosis II (i.e., Metaphase II). Then, after fertilization, Meiosis II finishes. This is associated with a Metaphase Plate being seen on histology. Chromosomes are lined up on the metaphase plate. Tells clinician that egg is ready to be fertilized. - After the LH surge, the oocyte completes meiosis I (because LH stimulates meiosis inducing factor production by granulosa cells). 2. The second polar body is seen after fertilization. KNOW THAT!!! This is formed when the egg has completed Meiosis II, which happens after fertilization.

1. 53 y/o presents with irregular menstrual periods. She says her last period was a year ago and before that she went 2-3 months w/o a period. She also reports intermittent intolerance to heat. Blood tests show: • Low estrogen • High FSH and LH Which cell type is functioning abnormally: a) Endometrial cells b) Granulosa cells c) Oocytes d) Peg cells e) Pituitary gonadotropes 2. You are studying factors that stimulate mitosis in oocytes. What would be the best source of oocytes for this study? a) Antral follicles b) Atretic follicles c) Fetal ovaries d) Germinal epithelium e) Primary follicles 3. Normally, the immature oocyte is arrested in ____ and, in a normal cycle, ___ stimulates maturation so the oocyte can be fertilized. a) Anaphase I of Meiosis; FSH b) Prophase I of Meiosis; hCG c) Metaphase II of Meiosis; FSH d) Prophase I of Meiosis; LH e) Telophase I of Meiosis; FSH. 4. A woman comes to clinic trying to conceive first child. The physician answers a question by pointing out an area and saying that it secretes a hormone that changes the endometrium to the secretory state and raises body temperature. This structure is a(n) ___ and its product is ___. a) Antral follicle; testosterone b) Antral follicle; estrogen c) Corpus luteum; progesterone d) Corpus luteum; estrogen e) Primary follicle; progesterone Ovaries, Uterine Tube, and Uterus -- PI (1/4)

1. b) Granulosa cells - Granulosa cells produce aromatase, which forms estrogen. So there is low estrogen. FSH and LH are high, trying to increase estrogen. - This person is going through menopause. This causes high LH and FSH because there is no negative feedback from estrogen. 2. c) Fetal ovaries - Fetal ovaries would have true oocytes. Primary and Antral follicles would have stuff that has already undergone some processes. - Mitosis only occurs during fetal development; stops at birth. Fetal ovaries are the only site of mitosis. By the end of embryonic development, oocytes have entered meiosis. 3. d) Prophase I of Meiosis; LH - At birth, all oocytes are arrested in Meiosis I prophase until the LH surge. Then LH stimulates maturation of the oocyte. Not C because by that point, egg would be ready to fertilize. 4. c) Corpus luteum; progesterone - Probably know histology of corpus luteum. Definitely know role of progesterone in cycle. - COMMON BOARD TOPIC - Effect of estrogen vs. progesterone on the uterus.

1. Which of the following values reflect the normal physiological hemodynamic changes seen during pregnancy? a) Increased blood volume, increased SVR and PVR, increased heart rate; increased CO b) Increased blood volume, decreased SVR and PVR, increased heart rate; increased CO c) Decreased blood volume, increased SVR and PVR, increased heart rate; increased CO d) Increased blood volume, increased SVR and PVR, decreased heart rate; decreased CO 2. A woman in labor continues to be dilated 2 cm after two hours in labor. She is given a synthetic version of a hormone to help dilate her cervix. Where is the endogenous version of this hormone stored in the body? a) adrenal cortex b) anterior pituitary gland c) hypothalamus d) mammary glands e) posterior pituitary gland 3. A woman with a 2-year old son comes to her physician because she has been unable to conceive a second child for more than a year. The woman is currently breastfeeding her son. Which of the following best explains the physiologic mechanism that is preventing her from getting pregnant? a) Prolactin inhibits secretion of estrogen from the ovaries b) Prolactin inhibits secretion of follicle-stimulating hormone from the anterior pituitary gland. c) Prolactin inhibits secretion of gonadotropin-releasing hormone from the hypothalamus. d) Prolactin inhibits secretion of luteinizing hormone from the anterior pituitary gland. e) Prolactin inhibits secretion of progesterone from the corpus luteum. 4. A healthy 25 yo primipara at 38 weeks of gestation calls you reporting that she is in labor. She denies any complications of this pregnancy and tells you that her due date was established by her last menstrual period and confirmed by an 18-week ultrasound. Which of the following is true? a) She is soon to deliver a full-term baby. b) Conception occurred 36 weeks ago. c) Date of conception cannot be determined d) She is in the second stage of labor. Female Reproductive Physiology: Pregnancy and Lactation

1. b) Increased blood volume, decreased SVR and PVR, increased heart rate; increased CO - Increased blood volume, increased SVR and PVR, increased heart rate; increased CO. - Pregnancy is accompanied by an increase in plasma volume (leading to relative anemia), decreased SVR and PVR, increased heart rate leading to an increase in total cardiac output. - At the time of delivery, there is a further increase in CO. 2. e) posterior pituitary gland - Oxytocin is responsible for the dilation of the cervix and contraction of the uterus during labor, as well as milk let-down during breastfeeding. When labor is arrested, a synthetic analog (e.g. pitocin) may be applied topically to the cervix to facilitate dilation 3. c) Prolactin inhibits secretion of gonadotropin-releasing hormone from the hypothalamus. - Prolactin does not directly inhibit secretion of estrogen (a), FSH (b), LH (d) and progesterone (e). GnRH inhibition by prolactin results in decreased synthesis/secretion of LH and FSH, and hence, no ovulation. 4. Didn't specify in PPT, but should be in previous cards.

1. In an in vitro fertilization clinic, the retrieved oocytes are evaluated before fertilization. Under the microscope, the oocyte is ready for fertilization once which of the following are visible? a) Abundant cumulus cells b) A corona radiata c) A metaphase plate d) No zona pellucida e) Two polar bodies 2. Serum levels of ___ are assayed early in the cycle in infertility patients to detect the development of primordial germ cells to primary follicles. Rising levels of this hormone will stimulate ___. a) Androgens; Endometrial secretion b) Estrogen; Endometrial proliferation c) Estrogen; Endometrial secretion d) Progesterone; Endometrial secretion e) Progesterone; Endometrial proliferation 3. Day 13 of cycle. If only 1-2 follicles advance to ovulation, why develop 32 ovarian/antral follicles? They are needed for the production of: a) Androgens to directly stimulate FSH secretion from gonadotropes. b) Estrogens for positive feedback to GnRH neurons and gonadotropes. c) Progesterone to inhibit follicle stimulating hormone. d) Inhibin to maintain the uterine endometrium. e) Progesterone to stimulate proliferation of the uterine endometrium. 4. 23 y/o woman presents with an ectopic pregnancy. What is the most common site for an ectopic pregnancy? a) Proliferative endometrium b) Fallopian tube c) Secretory endometrium d) Cervix e) Vagina Ovaries, Uterine Tube, and Uterus -- PI (3/4)

1. c) A metaphase plate - Arrested again in metaphase of Meiosis II (Metaphase II).There will be a metaphase plate visible at this point. After LH surge, oocytes complete meiosis and arrests again in metaphase 2. The second polar body is seen after fertilization (KNOW THAT!!!), when the oocyte completes meiosis. All other cells will be there even if oocyte is ready for fertilization. - Two polar bodies would be after fertilization. There will still be a zona pellucida. Cumulus cells help the oocyte mature. 2. b) Estrogen; Endometrial proliferation - During follicular phase, estradiol rises from granulosa cells. This stimulates proliferation of the uterine endometrium. - IMAGE: Picture 1 shows development from primordial to primary follicle). 3. b) Estrogens for positive feedback to GnRH neurons and gonadotropes. - Estrogens give positive feedback to stimulate GnRH and LH. E is definitely wrong - that's estrogen. Androgens don't do A. C is wrong. Also, day 13, so look at what hormones would be high and low. 4. b) Fallopian Tube - Question asked us to choose correct picture without telling what the pictures were. - IMAGE: Picture 2: Fallopian tube - you can see peg cells and ciliated cells - so this is definitely the oviduct..

1. You are treating you patient with progesterone for infertility after she had an implantation defect. This was diagnosed by her failure to conceive, low serum progesterone, and a uterine biopsy on day 21 of her cycle which showed: a) Luteinized endometrium b) No antral follicles c) No peg cells in the epithelium d) Proliferating endometrium e) Secretory endometrium 2. Clomid, an estrogen receptor blocker, is often used early in treating infertility as it tricks the hypothalamic-pituitary axis into secreting more GnRH, LH, and FSH, thus increasing the number of ovulatory follicles. However, about 25% of these patients may produce embryos, but they fail to implant. This may be caused by endometrial: a) Apoptosis b) Hyperplasia c) Hypoplasia -- But why is there hypoplasia? d) Luteinization e) Decidualization 3. A failure in the following partnership can be diagnostic of anencephaly or a neural tube defect. This partnership is under the control of CRH from the hypothalamus and ACTH from the pituitary. Often, the diagnosis is made following a drop in maternal serum estrogens during the 3rd trimester. Which of the following describes this partnership? a) Androgens produced by the fetal adrenal cortex, which are aromatized to estrogens by placenta. b) Cortisol production by the fetal adrenal cortex, which is converted to estrogens in the placenta. c) Estrogen production by the fetal adrenal cortex from androgens produced by placenta. d) Progesterone production by corpus luteum of pregnancy, which is converted by the placenta. 4. Studies of placentas from fetuses with Trisomy 21 (Down's) show defects in the cytotrophoblast differentiation and delayed formation of the cellular region that is bathed in maternal blood. This defect also leads to the secretion of an abnormally glycosylated and weakly bioactive hCG along with a decrease in hCG receptors. The region that shows delayed development is the _____ and hCG target cells with low receptors in the ___. a) Decidua, Corpus luteum b) Fetal vascular endothelial cells, Antral follicles c) Fetal mesenchyme, Corpus luteum d) Synytiotrophoblast, Corpus luteum e) Syncytiotrophoblast, Granulosa cells

1. d) Proliferating endometrium - If you see mitotic figures in the endometrium on day 21, she has not ovulated and no corpus luteum has formed. To support the embryo, the endometrium must be in the secretory phase. Low progesterone means secretory phase (ovulation) can't start. Normally, day 21 would be secretory but she has low progesterone. 2. c) Hypoplasia - Estrogen is needed for endometrial proliferation. An anti-estrogen may block this and cause a thin endometrium. - Hyperplasia can be caused by estrogen pills, which can lead to cancer. - Decidualization describes the endometrium after implantation has occurred, so that will not be present. 3. a) Androgens produced by the fetal adrenal cortex, which are aromatized to estrogens by placenta. - KNOW THIS PARTNERSHIP (similar, but distinct from theca / granulosa partnership) 4. d) Synytiotrophoblast, Corpus luteum - Cytrotrophoblast joins syncytiotrophoblast and penetrates uterine wall and becomes bathed in maternal blood in lacunae. The syncytiotrophoblast produces hCG which is detected in a pregnancy test. hCG is like LH in that it stimulates the corpus luteum to secrete progesterone.

1. 31 y/o with no period. Low serum estradiol and androstenone. LH is high, but FSH is borderline. She is found to have an antibody targeting androgen-producing cells, and is diagnosed with autoimmune oophritis. The antibody likely targets: a) Corona Radiata b) Endometrium c) Granulosa cells d) Peg cells e) Theca cells 2. Same patient as last question with autoimmune oophoritis. She is also found to have high serum inhibin after ovulation induction with GnRH agonists. Multiple follicles had developed in the woman. The high inhibin likely caused the unexpectedly low ___, which should have been much higher considering the low estradiol. a) Androgens b) Follicle Stimulating Hormone c) Human Chorionic Gonadotropin d) Luteinizing hormone e) Progesterone 3. Which is correct about the hypothalamus-pituitary-ovarian axis? a) Estradiol, released by the ovary, exhibits positive feedback on the pituitary and gonadotrope which leads to the LH surge. b) Inhibin is released by the ovary as a negative feedback to the pituitary during the luteal phase of the follicle cycle. c) Hypothalamus releases FSH and LH to stimulate ovarian cells. 4. 22 y/o with irregular menstruation, acne, facial hair. She is diagnosed with polycystic ovarian syndrome. - Testosterone is high - Day 10 Estradiol is high - LH:FSH ratio is 5:1 (high; normal is 1:1) - Day 21 serum progesterone is low Considering her serum hormone levels, which structure is LEAST likely present? a) Antral follicle b) Atretic follicle c) Corpus luteum d) Primary follicle e) Primordial follicle Ovaries, Uterine Tube, and Uterus -- PI (2/4)

1. e) Theca cells - Theca cells are the only cells in the list that produce androgens. Granulosa cells do not have the needed enzymes. They can aromatize the androgens to produce estrogens. 2. b) Follicle Stimulating Hormone - Inhibin inhibits FSH, which should have been at high levels (close to post-menopausal levels), due to the low estradiol. 3. a) Estradiol, released by the ovary, exhibits positive feedback on the pituitary and gonadotrope which leads to the LH surge. - B is wrong: Inhibin is NOT released during the luteal phase. - C is wrong: FSH and LH are released by the pituitary. 4. c) Corpus luteum - Low progesterone is main clue. LH >>> FSH is a diagnostic feature. LH is trying to grow CL, but it ends up causing cysts. If the CL was present, progesterone wouldn't be low.

Histology of concurrent Paget's Disease of the nipple and Ductal Carcinoma in situ (DCIS) Breast Pathology

100% of mammary paget disease cases are associated with underlying DCIS. Many of them may have even invasive cancer. Always associated with DCIS. DCIS is associated with calcifications. So seen here too. Invasion into Epidermis -- Characteristic of Paget's - Makes sense -- paget's is visible on the epidermis Calcifications and Comedo necrosis - characteristic of DCIS

Ductal Carcinoma in situ: What Grade is the cancer if histology shows: - Proliferation of a uniform cell population - No nuclear overlap - Expansion of breast ducts due to cell invasion. Breast Pathology

<== NOTE: Wrong Image LOW GRADE DCIS Low grade DCIS shows complete expansion of at least two ductal units by uniform cell population. LOOK FOR EXPANSION OF DUCTS! Cancer cells cause this. Also, Calcifications Proliferation of uniform cell population. No nuclear overlap. There are many different morphologically subtypes, cribriform, solid, etc. Ductal carcinoma in situ means that the cancer cells are growing in pre-existing spaces. These structures are surrounded by basement membrane and should not invade. Uniform cell population, as opposed to pleomorphic cell population of high grade DCIS.

What happens as a result of an LH surge? Female Microanatomy/Reproductive Microanatomy PI

A massive increase in LH stimulate the oocyte to complete Meiosis I. This is ovulation. This forms the secondary oocyte. However, because of unequal cytoplasmic division, the result is one large oocyte and one tiny polar body, which is stuck to its partner. Then, the secondary oocyte is arrested again in meiosis II. This is a good sign that the oocyte is ready for fertilization. LH also breaks down the connective tissue so the oocyte can escape from the ovary. It stimulates fluid buildup which bulges against the ovarian wall and creates conditions for the break through by the oocyte. Allows ovulation.

++++++++++++++++++++++++ Molar Pregnancy (Hydatiform mole): - Karyotype abnormalities / etiology - Definition - What protein is markedly elevated? - Caused by defect in what process? - What is its major clinical sign? - Complete vs. Partial Molar Pregnancy Female Reproductive Physiology: Pregnancy and Lactation

A molar pregnancy is often accompanied by painless vaginal bleeding in the first trimester, larger uterus than normal for gestational age (e.g., fundal height above the uterus at only 10 weeks gestation), and markedly elevated hCG levels. It characteristically becomes symptomatic in the early months of pregnancy. Elevated hCG because this involves a problem with the placenta, and the placenta makes hCG. Caused by abnormal fertilization of egg. Chromosomes are abnormal. Karyotype might be diploid (e.g., 46 XX) or even triploid (e.g., 69 XXX or 69 XXY). Complete: Diploid - 46XX or 46XY; caused by sperm fertilizing an egg that has no maternal DNA, so there's no fetal tissue here since maternal DNA is needed for fetal tissue growth. hCG is VERY high. Partial: Triploid - 69XXX, 69XXY, or 69XYY. Caused by two sperm fertilizing one egg. There is some maternal DNA here, so fetal tissue is present. hCG levels are moderately elevated, not elevated as much as a complete.

Theca cells of ovaries produce ___ in response to what hormone? Granulosa cells respond to __(hormone)__ to produce __(enzyme)__ which does what? Which ovarian follicular cells respond to: - FSH - LH How is estrogen produced? How are GnRH and LH produced? LH tells theca cells to produce ___. FSH tells granulosa cells to release ___. FSH also stimulates production of ___ and ___, which feed back to the pituitary to inhibit FSH. (Follicular Phase -- Follicle Formation) Female Microanatomy/Reproductive Microanatomy PI

A partnership develops between the Theca externa and Theca interna cells and the granulosa cells. - Theca cells produce androgens in response to luteinizing hormone (LH). - Granulosa cells respond to follicle-stimulating hormone (FSH) mainly by aromatizing androgens to estrogens and to some extent by producing pregnenolone from cholesterol. LH ==> Theca cells ==> androgens. FSH ==> Granulosa cells ==> aromatase Thus, as follicles enlarge and develop, during "follicular phase", estrogen rises. GnRH Promotes the synthesis of GnRHR and the luteinizing hormone (LH) surge. - LH stimulates theca cells to produce testosterone! - FSH stimulates granulosa cells to release estrogen - FSH also stimulates production of inhibin and estrogens, which feedback to the pituitary to inhibit FSH. Wikipedia: The theca interna cells express receptors for luteinizing hormone (LH) to produce androstenedione, which via a few steps, gives the granulosa the precursor for estrogen manufacturing. "Lets review" - Estrogen positive feedback stimulates GnRH neurons to stimulate the release of LH, which stimulates theca cells to produce androgens. - These androgens are passed to the granulosa cells to be converted to estrogens. In the meantime, the gonadotropes are also producing FSH to stimulate granulosa cells to secrete and grow. Eventually they secrete enough inhibin to limit FSH secretion. The number of follicles is thereby limited.

Which prenatal diagnostic test can measure alpha-feroprotein (AFP) and thus provide information about neural tube defects? Which one can only reveal chromosomal abnormalities? Preconception and Prenatal Genetics

Amniocentesis - Can dx NTDs (measures AFP) - Sample of amniotic fluid - Typically done after 15 weeks of gestation Chorionic Villus Sampling: - No NTD information (measures AFP) - Bx of placental tissue - Typically done 10-13 weeks of gestation

What happens to the unused female follicles? Female Microanatomy/Reproductive Microanatomy PI

Atresia AKA apoptosis. Females are born with more follicles than they will ever need. IMAGE: This is an example showing a normal developing follicle next to an atretic follicle and the lower figure shows that all that is left is the "zona pellucida".

Acute Mastitis: - What is it? - What are the 2 most common bacteria? Breast Pathology

Bacterial infection of breast ducts: - Cracks in the skin of the nipple or stasis of the milk in lactating women may allow direct or retrograde ductal spread of bacteria Staphylococcus aureus or Streptococcus pyogenes

What stage of the cell is implanted into the uterine lining? Female Microanatomy/Reproductive Microanatomy PI

Blastocyst During implantation, the blastocyst separates itself from the zona pellucida.

Mammogram appearance of Invasive Breast Cancer Breast Pathology

Calcifications are present - star-like appearance (stellate) Malignant lesions tend to grow up, so more tall than wide. Benign lesions tend to grow parallel, so more wide than tall.

(Conceptual) What are the two major Prenatal Diagnostic Tests? What makes these tests diagnostic, rather than screening tests? Preconception and Prenatal Genetics

Chorionic Villus Sampling Amniocentesis These are invasive procedures, unlike the screening tests. You are actually getting a tissue sample, but you can get better information. Available to all women, but recommended if there are significant risk factors, such as older maternal age.

What 2 types of blast cells are responsible for supplying nutrients to the blastocyst around the time of implantation? What major hormone can one of these secrete? Female Microanatomy/Reproductive Microanatomy PI

Cytotrophoblasts and Syncytiotrophoblasts Syncytiotrophoblasts are within Cytotrophoblasts The syncytiotrophoblasts of the placenta produce human chorionic gonadotropin (hCG, identical to LH) which maintains the corpus luteum for about 60 days. - This is the hormone detected in pregnancy tests.

Diagnose: - Most common tumor in adolescent and young adults - Occurs in early teens to 70s - Well defined mass; mobile - Average size less than 3 cm. - Waxes/Wanes: Changes with menstrual cycle or other hormonal changes. Breast Pathology

Fibroadenoma Fibroadenomas are hormone sensitive. So they get much bigger during pregnancy; might be in clinical presentation.

Primary oocytes, produced from primordial follicles, get stuck in the ___ phase of meiosis I. Female Microanatomy/Reproductive Microanatomy PI

Diplotene - Prophase The primordial follicle next becomes a Primary follicle, which also contains an oocyte that is arrested in Meiosis I. They stay arrested here until ovulation. Thus they can stay arrested in Meiosis I for decades! At this point, they are surrounded by layers of follicular cells. What is Diplotene? During this phase of meiosis, the two homologous chromosomes migrate apart. Hence, Diplotene. The chromosomes are far away from e/o now.

First Trimester Screening test - Interpretation of results: • Down Syndrome will have ↑ or ↓: - Nuchal translucency (NT) - PAPP-A (pregnancy-associated plasma protein A) - Free beta hCG levels • Trisomy 18 (Edward's Syndrome) will have ↑ or ↓: - Nuchal translucency (NT) - PAPP-A (pregnancy-associated plasma protein A) - Free beta hCG levels Preconception and Prenatal Genetics

Down Syndrome: ↑ NT (more translucent) ↓ PAPP-A ↑ Free beta hCG levels Trisomy 18: ↑ NT ↓ PAPP-A ↓ Free beta hCG levels NOTE: She said we don't need to know about beta hCG and PAPP-A for her test Q's. Focus on NT. High nuchal translucency is a big marker for Down's syndrome, but is also present in other conditions. Nuchal Translucency is basically a measurement of the amount of fluid behind the dorsal aspect of the fetus's head. The bigger that space is, the worse off the fetus will be. You have to get very special training to be able to perform this test. Even Dr. Sward said she's not qualified to do it. beta hCG: beta subunit of hCG - beta-hCG is what pregnancy tests measure

Second Trimester Screening: Quadruple Screening: Down's syndrome vs. Trisomy 18 vs. Neural Tube Defects will have increased or decreased levels of each of these? - α-fetoprotein (AFP) - estriol (uE3) - inhibin A (DIA) - total hCG Preconception and Prenatal Genetics

Down's Syndrome: ↓ α-fetoprotein ↓ estriol ↑ inhibin A ↑ total hCG Remember: high (hCG, inhibin); deficit (estriol, fetoprotein) QUAD Screening: - Consists of blood draw to measure levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and dimeric inhibin A (DIA). - Reports a risk ratio for open neural tube defects, Down syndrome, and trisomy 18. - AFP (as you can see in image) is measured to check for neural tube defects. - Incredibly important that correct gestational age is determined because all of those proteins change levels throughout preganancy, so you have to be able to compare it to the correct normal value. IMAGE: Black circle means it doesn't matter / that test doesn't tell you about that DZ.

++++++++++++++++++++ Diagnose: - Heterogenous lesion seen on histology and radiology - Rarely involve axillary lymph node metastasis - Don't always progress to invasive cancer - However, present in at least 80% of invasive breast cancers. Breast Pathology

Ductal carcinoma in situ In situ - consistent with lack of metastasis / spread.

General / Conceptual What is the oviduct? Fimbria? Ampulla? Female Microanatomy/Reproductive Microanatomy PI

Fertilization and Transport: • Fertilization occurs in ampulla of oviduct • The oocyte completes meiosis and the pronucleus joins with the sperm pronucleus, restoring the diploid state. • The zygote is then transported to the uterine lumen. • The embryo develops to the morula and blastocyst stages and implants as a blastocyst Oviduct is also called the uterine tube. Has 3 layers: - Outer: serosa (squamous mesothelium + connective tissue) - Muscular layer (Outer longitudinal and inner circular smooth muscle) - Lumen - Mucosa: Lamina propria (connective tissue) and Epithelium (thrown into folds; simple columnar, ciliated). Two types of cells: Peg cells and Ciliated cells (next card).

First Trimester Screening Test: (Prenatal Screening Test) Consists of: - an Ultrasound to measure ___. - Blood Test to measure ___ and ___. Reports the risk for ___ and ___ (what 2 conditions?). Preconception and Prenatal Genetics

First Trimester Screening: - Supposed to be given to all pregnant women, regardless of age. - In the first trimester screening, you measure nuchal translucency, PAPP-A, and beta hCG. Consists of: 1. Ultrasound - to measure nuchal translucency (NT). 2. Blood test - to measure pregnancy-associated plasma protein A (PAPP-A) and free beta hCG levels. Reports the risk for: 1. Down syndrome 2. Trisomy 18 So a pregnant woman in first trim will go to clinic, get an ultrasound and blood test, and leave knowing the risk for Down Syndrome and Trisomy 18. The doctor will have measurements of nuchal translucency, PAPP-A, and free beta hCG levels.

What occurs during the three stages of labor? Female Reproductive Physiology: Pregnancy and Lactation

First stage - dilation of the cervix. >> Latent phase (0-4 cm dilated) >> Active phase (4-10 cm dilated) Second stage - fully dilated till expulsion of the fetus. Descent of the head. Third stage - following expulsion of the fetus until the placenta and membranes are delivered.

Of all the follicles, only 1-2 will ovulate. These are called the Dominant Follicles. The best way to know which one is dominant and will ovulate is that it will have: 1. What size? 2. the highest level of ___. Why? 3. a high ___:___ ratio. Why? MNEMONIC Female Microanatomy/Reproductive Microanatomy PI

First, the dominant follicle should be very large; maybe the largest. Highest INHIBIN level will be dominant follicles. - Highest inhibin will best inhibit FSH. - The fall in FSH allows smaller follicles to die off. They are, in effect, "starved" of FSH. Estrogen:Androgen ratio should be HIGH. - i.e., they will have more estrogen than androgen (estrogen >>> androgens) - makes sense -- want the follicle to produce a lot of estrogen, which is needed to support implantation. Don't really need androgen. - So the dominant follicle should have more granulosa cells than theca cells. MNEM: The dominant follicle has more granulosa cell and fewer theca cell properties -- high inhibin and estrogen, low androgen.

++++++++++++++++++++++++ Correlate each hormone with the phases of the Ovarian cycle: - Estrogen - Progesterone - FSH - LH Female Microanatomy/Reproductive Microanatomy PI

Follicular Phase: • Follicles release estrogen, which causes the uterine wall (endometrium) to thicken. Ovulation: • Follicles rupture and the Corpus Luteum develops. This secretes large amounts of progesterone (and small amounts of estrogen). Luteal Phase: • Progesterone and estrogen are released from the corpus luteum and thicken the endometrium. Menstruation: • The endometrium is sloughed away when the Corpus Luteum degenerates. Progesterone and Estrogen fall, allowing FSH to surge to promote formation of new follicles. - Estrogen, LH, and FSH are high right before ovulation, and then drop. - FSH is the only hormone high during the menstrual phase. - Progesterone surges during the luteal phase

+++++++++++++++++++++++++++ How do the phases of the Ovarian Cycle correlate with the phases of the Endometrial cycle? Female Microanatomy/Reproductive Microanatomy PI

Follicular Phase: First half of the endometrial cycle. - Mentrual and Proliferative phases. Luteal Phase: Second half of the endometrial cycle. - Secretory phase.

2 layers of the uterine wall - Function, Location, and arterial supply of: - Functional layer (Functionalis) - Basal layer (Basalis) Female Microanatomy/Reproductive Microanatomy PI

Functional Layer: External layer - Supplied by coiled arteries - Sloughed during menstrual phase. Basal Layer: Internal layer - Supplied by straight arteries - Gives rise to new functionalis each cycle.

Define: - Gestational age - Embryonic age Female Reproductive Physiology: Pregnancy and Lactation

Gestational Age- calculated from date of last menstrual period Embryonic Age- calculated from date of conception (gestational age minus 2 weeks)

Histology of uterus during the secretory phase: What characteristic marker is diagnostic of ovulation? Female Microanatomy/Reproductive Microanatomy PI

Glycogen droplets under the nuclei Also, those glands (white areas) are coiled. In the other phases, they are straight. Makes sense because this is the secretory phase and those glands can now secrete nutrients needed for a potential embryo. If you saw a lot of mitotic figures on day 20, for example, what would this suggest? - Ovulation has not occurred. Mitotic figures are characteristic of the proliferative phase.

What epidermal growth factor mutation is associated with poor prognosis of breast cancer and a short disease-free survival time, regardless of node metastasis? Breast Pathology

HER-2-Neu

Ductal Carcinoma in situ: What GRADE is the cancer if histology shows: 1. Linear, branching Calcifications 2. Nuclear enlargement and pleomorphism 3. Comedo necrosis Breast Pathology

High Grade (Grade III) DCIS 1. Linear, branching Calcifications 2. Nuclear enlargement and pleomorphism 3. Comedo necrosis Pleomorphic cell population, as opposed to uniform cell population of low grade DCIS.

++++++++++++++++++++++++++ Women who do not breast feed may resume menses within 5-7 weeks post-delivery while those who breastfeed return to menses generally longer (within 36 weeks post-delivery) -- WHY? Female Reproductive Physiology: Pregnancy and Lactation

High prolactin and very low Estrogen (E) and Progesterone (P) during regular lactation (compared to pregnancy); very low levels of E and P USUALLY results in amenorrhea and cessation of menstrual cycles. WHY?? Prolactin (from anterior pituitary) prevents ovulation (hence, case of amenorrhea) by inhibiting the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, thus inhibiting LH and FSH secretion from the anterior pituitary; decreased FSH results in lower estrogen. If a woman does not breast feed, prolactin won't be as high, and ovulation / menses can occur earlier.

+++++++++++++++++++ Hormones during Pregnancy: - Trends of hCG, estrogen, and progesterone throughout pregnancy. - Important: Where is progesterone made in early pregnancy, and what takes over progesterone and estrogen production between weeks 6-9? - Human Placental Lactogen: Made where? What does it do for the fetus? -- Causes production of what hormone in the mother to support fetal nutrition? Peaks in early or late pregnancy? - Relaxin: Made by ___ and ___. Causes what? Appears around weeks __-__ of pregnancy and keeps being produced until birth. Female Reproductive Physiology: Pregnancy and Lactation

Hormone trends: Image - hCG peaks around weeks 8-12 and then decreases to a stable level. - Estrogen and Progesterone are low in early pregnancy and increase to a high level during late pregnancy. Important: (1) The fetal cells (trophoblasts) that make up the placenta convert cholesterol from the mother's bloodstream into progesterone. (2) The conversion of cholesterol to pregnenolone by cytochrome P450scc (CYP11A1) occurs in placental mitochondria. (3) Between weeks 6-9 of pregnancy, the placenta takes over from the ovaries (luteal to placental shift) as the main producer of maternal Progesterone as well as estrogen and this continues through pregnancy. Other Hormones 1. Human placental lactogen (aka human chorionic somatomammotrophin, hCS)- made by the placenta (syncytiotrophoblast) and exert metabolic functions (increase maternal insulin production) to support fetal nutrition; increase to maximal levels at late pregnancy 2. Relaxin (ovary and placenta)- causes relaxation of the pelvic ligaments (to allow for expansion to support the developing fetus) and cervix (for delivery); appears between weeks 7-10 and remain throughout pregnancy

++++++++++++++++++++++++++++++++++++++ Hypothalamic-Pituitary-Ovarian (HPO) Axis: Females - What sex hormone is released by the Hypothalamus? - What 2 sex hormones are released by the Pituitary? - What sex hormones are released by the Ovaries? Positive and Negative feedback in the HPO axis. - Children vs. Adults -- how much hormone is needed for feedback? Female Physiology Before Pregnancy and Female Hormones

Hypothalamus: Gonadotrophin Releasing Hormone (GnRH) - release is pulsatile Anterior pituitary: Luteinizing Hormone (LH) Follicle Stimulating hormone (FSH) Ovary (Follicle= Theca cells, granulosa cells): Estrogens Progestins Androgens Inhibin Activin Follistatin Hormones released by the ovaries (e.g., estrogen) feed back to both the hypothalamus and pituitary. - Decreased production of LH and FSH - In children, low levels of steroid blocks release of gonadotropins LH and FSH from anterior pituitary. So in children, it's easy to keep sex hormones down. - In adults, requirement for much higher levels of steroids for the same level of inhibition of LH and FSH release from anterior pituitary. So in adults, there are more sex hormones.

What happens to the risk of down syndrome or other chromosomal abnormalities as an older pregnant woman moves from 1st ➜ 2nd ➜ 3rd trimester ➜ live birth? Define aneuploidy. Preconception and Prenatal Genetics

If the woman is >35 y/o, there is a high risk for chromosomal abnormalities in the first trimester. That risk goes down if the woman makes it to the later trimesters, and especially live birth, because fetuses with chromosomal abnormalities often undergo spontaneous abortion. So the further your fetus has made it, the less likely chance that they have a chromosomal abnormality. IMAGE: Don't memorize chart. Just get that^ take-home message: E.g., (highlighted in pink) if mom is 42, 1st trim is 1/32 chance, 2nd trim is 1/38 chance, and live birth is 1/54 chance. Aneuploidy: the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes. A cell with any number of complete chromosome sets is called a euploid cell.

What histological characteristic means that breast cancer is invasive? Breast Pathology

In order for it to be "invasive" they must break through the basement membrane. Once it breaks thru basement membrane, it is invasive. Now it can invade lymphatics and vasculature. If cancer is invasive, there isn't really a way to cure it.

++++++++++++++++++++++++++ Determiantion of Sex in Gametes: Which of these features will be present if testis vs. ovaries develop? - Medullary cords - Cortical cords - Tunica albicans Define in terms of M vs. F: - Sertoli cells - Follicular cells Embryonic Development of Gonads and Duct Systems

Indifferent gonads --Y chrom.--> testis (sertoli cells) Indifferent gonads -- no Y --> ovaries (follicular cells) Sertoli Cells (become male testis): ✔ Medullary Cords develop ✔ Thick tunica albicans develops ✘ No cortical cord Follicular Cells (become ovaries): ✔ Cortical cord develops ✘ No Medullary Cord ✘ No tunica albicans i.e., Males get a Medullary Cord, while females get a Cortical Cord. Males have a tunica albicans, females do not.

Fate of parts of the early embryo: - What does the Inner Cell Mass (ICM) become? - What do Trophoblasts become? - What are the roles of the Cytotrophoblast vs. the Syncytiotrophoblast? Female Reproductive Physiology: Pregnancy and Lactation

Inner Cell Mass (ICM) develops into the embryo/fetus Trophoblasts (TE) eventually forms the fetal component of the placenta - Cytotrophoblast is the inner layer of trophoblast - Syncytiotrophoblast- the outer layer of the trophoblast; it actively invades the uterine wall, rupturing maternal capillaries, to establish an interface between maternal blood and embryonic extracellular fluid and thus, facilitate exchange of material between the mother and the embryo. Blastocoel: Fluid-filled Cavity

++++++++++++++++++++ Diagnose: - Benign mass, often in central part of the breast. - Bloody nipple discharge - Usually solitary Breast Pathology

Intraductal Papilloma Bloody nipple discharge because it's inside the ducts. Blood can leak out through the nipple. Benign Usually solitary but can be multiple

What is the first site of breast cancer metastasis? Breast Pathology

Ipsilateral axilla If the axillary lymph nodes are involved, the cancer is invasive. Very bad news. Spreads through lymph nodes and goes straight to the axillary lymph nodes on the same side as the breast cancer. Once metastasis has occurred, CANCER CANNOT BE CURED.

After ovulation, the ___ phase begins. Role of LH -- stimulates production of what hormone? The corpeus luteum: what happens if there is preganancy vs. there is no pregnancy? Female Microanatomy/Reproductive Microanatomy PI

LH surge stimulates conversion of the remaining follicular cells to form a Corpus luteum. Theca and granulosa cells interact in the corpeus luteum. LH also stimulates the production of progesterone by both theca and granulosa cells in the corpeus luteum, which rises to stimulate the uterine endometrium and prepare it to receive an embryo. Estrogen is also high as it helps prepare body for pregnancy. High progesterone and estrogen feeds back negatively on GnRH neurons and LH and FSH to shut down gonadotropin stimulation. So, without any LH, Corpus luteum life is limited to 16 days, unless there is a pregnancy with a placenta that produces Chorionic gonadotropin, which is similar to LH. There are two things important about the corpus luteum. First, it must be maintained by LH or its equivalent from the placenta. The placenta form is called human chorionic gonadotropin or hCG. So, if there is a pregnancy, the corpus luteum will be maintained by hCG and that is the gonadotropin detected by the pregnancy test. If there is no pregnancy, then the CL has only 14-16 days to live. Why? Because estrogen and progesterone are inhibiting pituitary LH and FSH. The only thing that can save the CL is hCG.

Diagnose the Breast Cancer category: - positive for estrogen receptor - Low proliferation and spread - Will NOT respond to chemotherapy, do not give it to them. - Best treated by anti-hormonal treatments: Tamoxifen - Tend to grow slowly Breast Pathology

Luminal A "Luminal" = positive for estrogen receptor

Diagnose the Breast Cancer category: Estrogen receptor positive Higher proliferation index; Metastasis Younger age at diagnosis Larger tumor More often positive lymph node as compared to luminal A. Breast Pathology

Luminal B "Luminal" = positive for estrogen receptor There's also Luminal C, but not really emphasized. Obviously worse though. This differs from Luminal A in that it has rapid proliferation and growth.

Clinical presentation of Invasive Breast Cancer: Signs that breasts have developed cancer - lump characteristics - symmetry - skin changes - Define Paget skin changes Breast Pathology

Lump that does not move around. Paget: Eczema-like changes on nipple. If pt does not respond to steroid (for eczema), time for a bx. Look for asymmetry. "Very very important"

When do germ cells undergo meiosis to become haploid in males vs. females? Embryonic Development of Gonads and Duct Systems

Males: Meiosis starts at puberty, then continues for life. Females: Starts as a fetus. Arrests twice (see Image).

Chlamydia: Clinical Presentation - GU symptoms of urethritis and cervicitis caused by chlamydia. - Chlamydia also has what sequelae outside of the GU system? - Classic triad of chlamydia presentation Sexually Transmitted Infections I: Chlamydia and Neisseria

Most cases of chlamydia (70-80%) are totally asymptomatic with normal physical exams. If there are symptoms, Chlamydia can cause Urethritis (M&F) or Cervicitis (F)... Urethritis - Occurs in men and women - Dysuria, discharge - Chlamydia causes 30-50% NGU (Non-Gonococcal Urethritis) in men Cervicitis - Vaginal discharge, painful sex, irregular bleeding - Chlamyida most common identified cause of Cervicitis. - Up to 10% have cervical discharge/friability Classic Triad: 1. GU infection (urethritis or cervicitis) 2. Arthritis 3. Conjunctivitis Sequelae of Chlamydia: - CONJUNCTIVITIS - gets in eyes - Oropharyngeal (mouth / throat) infection; sore throat. - Rectal infection - Epididymitis in males - PID in females. Can cause infertility. - Arthritis: reactive arthritis from infection of joints.

Embryologic origin of the female oviducts, uterus, cervix, and upper vagina. Embryologic origin of the male seminal vessicles, epididymis, and vas deferens. Female Physiology Before Pregnancy and Female Hormones

Mullerian Ducts - female parts Wolffian Ducts - male parts

What is "Triple Negative" Breast Cancer? Negative for what 3 things? Most of these cancers have spread where? Why does this have a bad prognosis? Survival improves if they make it to __ years with triple negative breast cancer. Breast Pathology

Negative for: 1. Estrogen receptor 2. Progesterone receptor 3. HER2 receptor - HER2 definition: promotes the growth of cancer cells (human epidermal growth factor receptor 2). -- There are particular medications that can target this and treat HER2 positive BrCa. Most are lymph node positive (spread to lymph node) Difficult to treat. Can't give them anti-hormonal drugs or anti-HER2 drugs. Image: Recognize that at 60 months (5 years), curve flattens out. So if patients make it to 5 years with cancer, their chance of survival goes way up.

In a mature placenta, is there intermingling of maternal and fetal blood? The placenta secretes what 2 hormones? Female Reproductive Physiology: Pregnancy and Lactation

No The placenta is a unique vascular organ that receives blood supplies from both the maternal and the fetal systems and thus, has two separate circulatory systems: (1) the maternal-placental (uteroplacental) blood circulation, and (2) the fetal-placental (fetoplacental) blood circulation. Placental Hormones: - Progesterone - Estradiol (mostly produced on fetal side)

Formation of the Secondary Follicles (Antrum) - What is the antrum? (Follicular Phase -- Follicle Formation) Female Microanatomy/Reproductive Microanatomy PI

Once the antrum is present, it is a secondary follicle. Antral Follicle is synonymous with Secondary Follicle. Granulosa cells secrete follicular fluid into the intercellular spaces and these eventually coalesce to form fluid pouches (blue in IMAGE) in the follicle called the antrum. You can see the formation in this cartoon. As the follicle grows, a layer of granulosa cells continue to be wrapped around the oocyte facing the antrum fluid. They continue to protect and nourish the oocyte. The formation of a fluid-filled cavity adjacent to the oocyte called the antrum designates the follicle as an antral follicle. An antral follicle is also called a Graafian follicle. The antrum is, of course, filled with follicular fluid.

Changes in the egg from follicle to oocyte throughout the menstrual cycle Granulosa cells produce what? Theca cells produce what? Both produce ___ to start ovulation. Female Physiology Before Pregnancy and Female Hormones

Only one follicle at each menstrual cycle will completely develop to give rise to a mature oocyte which can then be fertilized 1. Premordial follicle: simple oocyte surrounded by a single layer of granulosa cells 2. Primary follicle: more granulosa cells and a zona pellucida form 3. Seconday follicle: fully grown oocyte 4. Antral follicle: Antrum develops; theca interna develops 5. Graffian follicle: oocyte, granulosa cells, theca cells - pre-ovulatory - comes from the dominant follicle; this will be ovulated and can be fertilized 6. Corpus luteum forms after ovulation Antral follicles are mainly producing estrogens (source is granulosa cells) and androgens (source is theca cells): - Granulosa cells: produce estrogen - Theca cells: produce androgens - Theca and granulosa cells and two hormones (LH, FSH) are required for estrogen biosynthesis. Theca cells provide androgens to granulosa cells to make estrogens. At the LH surge, the theca and granulosa cells both make progesterone which is essential to ovulation.

++++++++++++++++++ Diagnose: - The epidermis shows an infiltrate of single or small groups of large pleomorphic cells, which have a large amount of clear cytoplasm. - They may be PAS positive. The tumor cells express EMA, CK7 and CAM 5.2, 90% of tumor cells express HER 2-NEU > Know the histology of this. > 100% of patients have ___. > 35-50% of patients have ___. Breast Pathology

Paget's Disease of the Nipple - 100% of patients have associated DCIS - 35-50% of patients have associated invasive carcinoma. Histology: Know this histology. When they grow into the epidermis, that is pagetory growth.

+++++++++++++++++++++++ Compare microscopic appearances of ciliated and peg cells in oviduct mucosal epithelium Female Microanatomy/Reproductive Microanatomy PI

Peg Cells: Longer nuclei, peg shape Ciliated cells: Circular nuclei, cilia in lumen In the images deck

Virilization of Female Infants (female pseudohermaphroditism) is caused by lack of what placental enzyme? Female Reproductive Physiology: Pregnancy and Lactation

Placental Aromatase (P450) Insufficiency -Placental aromatase deficiency prevents the placenta from converting androgens to estrogens, and results in excessive androgen levels -The above leads to ambiguous genitalia in female fetuses and virilization in pregnant mothers (since androgens cross the placenta). - Masculinization in female fetuses results in deficiency in synthesizing estradiol at puberty.

Preeclampsia: - Define - Characterized by: ___ BP and High ___ in urine - Likely etiology - Major risk factors Female Reproductive Physiology: Pregnancy and Lactation

Pre-eclampsia refers to hypertension and proteinuria (>300 mg/24 h); acute onset after 20 weeks of gestation in previously normotensive women Elevated liver enzymes, hemolytic anemia, low platelets in severe cases Hypothesized to be due to abnormal development of the placenta, leading to placenta ischemia and release of factors that cause maternal endothelial dysfunction Risk factors- first pregnancy; > 35 years of age; African-American; obesity; type 2 diabetes, pre-existing renal disease

MedBullets overview of prenatal oogenesis Female Microanatomy/Reproductive Microanatomy PI

Pre-natal oogenesis: • Oogenesis, which is maturation of oocytes, begins in fetal life. - primordial germ cells migrate from fetal hind gut to gonadal ridge >> primordial germ cells differentiate to oogonia - in fetal ovary, oogonia proliferate by mitotic divisions >> by week 20, proliferation ends and oogonia numbers peak at 7 million - oogonia (2N, diploid) differentiate to primary oocytes (2N, diploid) >> primary oocytes begins meiosis I and arrest in prophase I >>>> primary oocytes arrest in "dictyotene stage" until just before ovulation >>>> primary oocyte is surrounded by pre-granulosa cells in primordial follicle

Explain the differences between Prenatal Screening Tests and Prenatal Diagnostic Tests for fetal aneuploidy. What are the major tests in each? Preconception and Prenatal Genetics

Prenatal Screening Test - estimates the risk of a certain condition, based on information about the pregnancy. - Does not actually look at the chromosomes. Just uses information about the pregnancy and aligns it with statistics to provide general information to the parents. - Does not involve a tissue sample from the fetus, so non-invasive. - e.g., First trimester screen, Quad screen, Non-Invasive Prenatal Testing, Ultrasound. Prenatal Diagnostic Test - confirms the presence of a certain condition by actually getting a particular tissue sample from the fetus and looking at the chromosomes to check for a specific genetic changes. - This can actually diagnose a condition. - Since you're taking a tissue sample, these are invasive procedures. - e.g., Chorionic Villus Sampling, Amniocentesis, PUBS. Now, we'll go over the screening tests, and then the diagnostic tests. "Screening vs. Diagnostic tests is important to remember."

What is a primordial follicle? Structure? Mitosis? Female Microanatomy/Reproductive Microanatomy PI

Primordial Follicle: Primary oocyte + One layer of squamous follicular cells "Primordial" - present since beginning. Primordial follicles are most numerous in the embryonic/fetal ovary. They contain an oogonium which is dividing by mitosis ONLY in the embryo. Mitosis ends at birth. They are surrounded by one layer of flattened epithelial cells. A number of those primary oocytes will undergo Meiosis I, but will be arrested in the diplotene phase of Meiosis I. The ovary has lots of primordial follicles, however mitosis has stopped and many of the oocytes are undergoing atresia, or programmed cell death. At menarche, we will have only 400,000 oocytes, however, women only need 450 in a lifetime.

Name the origin and the route of the primordial germ cells destined to become oocytes and spermatocytes. - Originate from the ___. - Travel along the ___. - Eventually make it to the ___ where they become gonads. i.e., What is the migration pathway of these germ cells? Start from where, migrate up the ___, and eventually get to the ___ where they become gonads. Embryonic Development of Gonads and Duct Systems

Primordial germ cells destined to become spermatocytes or oocytes are born in the yolk sac and migrate along the hindgut to the genital ridges, where they grow into the gonads. Their destination is the genital ridge where the ovaries and testes will eventually develop. This ridge lies on either side of the hindgut. Migration pathway: - Migrate from yolk sac - Migrate up the hind gut - Migrate to the genital ridges, where they become the gonads.

Hormonal Control of Lactation: 1. Which hormone stimulates milk production in the epithelial cells of the breast? 2. Which hormone stimulates myoepithelial cell contraction to enable milk produced to be ejected from the gland? Clinical Correlation: Expected sxs of a prolactinoma. Female Reproductive Physiology: Pregnancy and Lactation

Prolactin (secreted by the Anterior pituitary) stimulates milk production in the epithelial cells of the breast. Oxytocin (stimulated by the Posterior pituitary) stimulates myoepithelial cell contraction to enable milk produced to be ejected from the gland. Clinical Correlation: Prolactinomas in women result in galactorrhea (production of milk), hypogonadism (estrogen deficiency) and hence, menstrual disturbance, infertility, and delayed menarche (adolescent girls)

How does maternal blood enter the intervillous space to provide blood to the embryo? Blood supply to embryo: - Initial - Later Female Microanatomy/Reproductive Microanatomy PI

Syncytiotrophoblast invade the endometrium and break down maternal vessels, causing maternal blood spills in these spaces. Invasion continues and this becomes the initial route for the maternal blood support. Thus, Embryo is nourished by lakes of maternal blood!! Eventually, Villi form, and these have vessels that will then provide blood to the embryo. (3rd week). Initial: Lakes of maternal blood Later: vessels in Villi

Give an overview of meiosis I and II, including what happens at each stage.

The Diplotene phase of Meiosis I is of particular importance because primary oocytes get ""stuck" here for a long time. During this phase, the two homologous chromosomes migrate apart. This is important to memorize because "you will need to know information about the arrested states of the oocyte along the pathway to ovulation and fertilization."

In males, the mesonephric duct turns into what 4 structures? (MNEM) Embryonic Development of Gonads and Duct Systems

The mesonephric ducts persist and are stimulated under the influence of the SRY gene. Develops into "SEED" structures: Seminal vesicles Efferent ductules Epididymus Ductus deferens The paramesonephric ducts (present in females) degenerate from the influence of the anti-mullerian hormone secreted by the Sertoli cells

During implantation of the blastocyst into the uterine wall: - A layer of ___ help the blastocyst break through and implant into the uterine wall. - What is Decidualization? ___ cells turn into decidual cells. What hormone does this require? - Clinical Correlation: Plan B and other abortive medications reduce levels of what hormone, preventing successful pregnancy? Female Reproductive Physiology: Pregnancy and Lactation

To implant: A layer of trophoblasts help the blastocyst implant. After implantation: - The uterine endometrial stromal cells differentiate into decidual cells (process is called decidualization) -- decidua lines the uterus during pregnancy; decidualization requires progesterone. - The decidua regulates embryo invasion of the endometrium and provides nutrition to the embryo. Clinical Correlation: Because progesterone is critical for pregnancy, early abortifacients and emergency contraception utilize agents that inhibit progesterone action: > Progesterone Receptor blockers (Mifepristone aka RU486)- prevents implantation of fertilized egg (by shedding of uterine lining) and also causing uterine contractions thus, terminating pregnancy vs. > "Plan B" is Levonorgestrel- high levels of progestin; prevents ovulation or fertilization (by altering transport of sperm and/or ova); also inhibits implantation by preventing endometrial receptivity

During which part of pregnancy does the mother: - Gain fat / weight - Develop insulin deficiency Female Reproductive Physiology: Pregnancy and Lactation

Weight gain: 1st half of pregnancy Insulin resistance: 2nd half of pregnancy. Due to: - Combined effects of antagonistic hormones (GH, PRL, hPL, glucagon and cortisol) - Maternal glucose use declines, gluconeogenesis increases, maximizing available glucose to fetus

Migration of Germ Cells: As germ cells migrate, they undergo genetic changes in order to become ___ cells. Embryonic Development of Gonads and Duct Systems

What to know: As the germ cells migrate, the undergo mitosis and remain diploid. They undergo a bunch of genetic changes in order to become TOTIPOTENT cells.

How is the corpeus luteum maintained after the LH surge / ovulation has ended, if there's a pregnancy? Female Microanatomy/Reproductive Microanatomy PI

hCG from the placenta acts like LH and maintains the uterus. hCG is produced by the placenta if there's a pregnancy. Corpeus Luteum secretes mainly progesterone, and also some estrogen. This shuts off pituitary gonadotropins. If there is no pregnancy, CL undergoes programmed cell death. No pregnancy, no pituitary maintenance. CL atrophies in about 14-16 days; progesterone and estrogen levels fall. Fall in progesterone and estrogen stimulate rise in FSH early in the next cycle, which stimulates new follicles.

Female Egg Development: First, give definitions of: - Primordial Germ Cell - Oogenia - Primary Oocyte - Secondary Oocyte - Mature Ovum - Polar bodies At what 2 points is meiosis arrested in female eggs? Female Microanatomy/Reproductive Microanatomy PI

https://www.youtube.com/watch?v=7C9JmIA0fbw - 5 minute summary Meiosis in the oocyte is arrested twice. First, when oogenia become primary oocytes. They will stay in Meiosis I until ovulated. Can be in Meiosis I for decades! Second, after ovulation, the oocyte is arrested in metaphase of Meiosis II until fertilization. 1. Primordial Germ Cells are present from the beginning. "Premordial" means present from beginning of time. These kick off development of eggs. 2. Primordial germ cells enter the ovaries early in fetal development to become Oogenia. 3. Oogenia become Primary Oocytes. 4. Primary Oocytes will then undergo meiosis to produce a Secondary Oocyte with a Polar Body. Polar bodies are small residuals with very little cytoplasm. All the cytoplasm went to the oocyte. This is where the processes of oogenesis and spermatogenesis differ. 5. Eventually, when the egg is fertilized by sperm, Meiosis II will create a mature Ovum + 3 polar bodies 1. Primordial Germ Cells → Oogenia 2. Oogenia — MITOSIS → Primary Oocytes. 3. Primary Oocyte — MEIOSIS → Secondary Oocyte + Polar Body. 4. Secondary Oocyte + Sperm — MEIOSIS → Ovum + 3 Polar Bodies.

+++++++++++++++++ HELPFUL +++++++++++++++++ The first half of the Ovarian reproductive cycle is called the Follicular Phase (AKA Proliferative Phase). What happens during this phase? - Role of Follicle Stimulating Hormone (FSH) - ___ cells secrete Estrogen, which promotes the growth of what? (proliferative phase) - Estrogen also, through feedback, promotes production of what hormone? - Those cells also secrete Inhibin, which uses a feedback mechanism to stop production of what hormone? - What hormone stimulates follicular growth? - What hormone prevents ALL the follicles from developing in one month? Female Microanatomy/Reproductive Microanatomy PI

• Follicles (sacs containing oocytes) within the ovary develop and mature to prepare for ovulation. This would be the first 14-16 days of the cycle. This phase is stimulated by Follicle stimulating hormone (FSH) early in the cycle. • Granulosa cells in the follicles secrete estrogen which stimulates the proliferation and growth of uterine glands (hence, proliferative phase of endometrium). Endometrium grows and basically reaches its max at ovulation, before it starts to shed. • Estrogen also has the role of positive feedback to the hypothalamus and pituitary to produce more GnRH, LH, and FSH to prepare for ovulation. Causes the LH and FSH spikes. Later, estrogen switches to negative feedback. • Granulosa cells also secrete inhibin, which provides negative feedback to the pituitary and by midcycle, inhibiting FSH, LH, and GnRH secretion (limits further stimulation so not all follicles develop in one month). • Development of follicles is facilitated by the interaction of granulosa cells with the oocyte. ❊ Follicle Stimulating Hormone "What hormone is stimulating follicular growth? That one is easy." - FSH stimulates granulosa cells to secrete estrogen. ❊ Estrogen Estrogen feeds back positively to promote GnRH and LH synthesis to prepare for the LH surge at midcycle (ovulation). Estrogen also stimulates the uterine endometrium to proliferate and grow the glands to get ready for a possible implantation. ❊ Inhibin However, you might ask....why don't ALL of the follicles develop in one month. The answer can be found in another product called inhibin. Inhibin is produced by granulosa cells to feedback to the pituitary gonadotrope and shut down FSH. So, this limits FSH production and prevents all follicles from starting this process.

Fertilization, Pregnancy, Parturition and Lactation: Important Events - Fertilization of the egg by the sperm takes place in what part of the oviduct? Then it travels to the __. Sperm attaches to which part of the egg? - What form of the egg is implanted in the uterine endometrium? - Define partuition. - Define Peurperium Female Reproductive Physiology: Pregnancy and Lactation

➣ Fertilization of the Egg by the Sperm - takes place in the ampulla of the Fallopian Tube, aka Oviduct. Then, the Fertilized Ovum is transported down the Fallopian Tube to the Uterus (3-5 days post-fertilization). Sperm enters the zona pellucida of the egg. Acrosome reaction occurs, allowing sperm make it into the egg easier. ➣ Then, implantation of the multi-cell Fertilized Ovum (Blastocyst) in the Uterine Endometrium (6 days after fertilization). Then: ➣ Placentation: Development of the Placenta. ➣ Gestation: Development of the Fetus ➣ Parturition: Birth of the Baby -- Yay!! ➣ Puerperium = Postpartum ➣ Lactation (Milk Production)