Reproduction

Menopause

-Around age 50, the ovaries run out of follicles (stop responding) -What happens to estrogen, GnRH and FSH levels production if there are no follicles? -> Estrogen levels fall -> Gnrh, LH, and FSH will increase -> No follicle to stimulate, so they won't produce estrogen -Perimenopausal females are less likely to ovulate. Why? -> The follicles that stay behind that they are ovulated last, tend to be the ones that are the least responsive to LH and FSH -> Not enough estrogen to set off the LH spike

Hormonal contraceptives

-Bring hormone levels up to a certain enough, that will inhibit GnRH production, which will then inhibit LH and FSH production, prevents you from developing a follicle , turn off your own body's production of estrogen -Adding exogenous hormones that change the endogenous production of a female's hormones. -What happens to GnRH, LH and FSH levels when taking the exogenous estrogen and progesterone? -> GnRH, LH, and FSH levels fall -What happens to endogenous production of estrogen? -> Endogenous levels of estrogen decreases -Does ovulation happen? What about proliferation of the endometrium? -> No, ovulation should not occur because there is not enough estrogen. Proliferation decreases so her periods may become lighter

Positive feedback loop: Labor

-Controlled variable: Muscle length -Stimulus: Stretch -Sensor: Mechanoreceptor -Input: Sensory neuron -Control center: Hypothalamus (posterior pituitary) -Output: oxytoxcin -Effectors: Uterus -Response: Smooth muscle contraction -Positive feedback: More stretch of the cervix -Delivery of the baby ends the feedback loop

Building a baby

-Egg is the largest cell in the human body, while sperm is the smallest cell in the human body -Around day 5 of development, the blastocyst moves into the uterus, ready for implantation -Egg has to diffuse and make its ways into the fallopian tube -Fluid filled cavity -Inter cell mass has to line up with wall of uterus in order for it to implant correctly -Only a few different cell division happen before specialization occurs into different kinds of cells

Uterine events

-Endometrial changes during female cycle Menstruation -Loss of thickened endometrium Proliferative phase -Thickening and growth or endometrium -When you are developing those follicles, those follicles begin producing estrogen that talks to the endometrium and gets it to grow -Now once you have selected the follicle, ovulation happens Secretory phase -Organ changes into a gland that produces sugar, egg with implant into side of uterus and won't have blood supply right away, puts glucose inside the uterine lining and feeds that growing embryo until it reaches a blood supply -Starts producing hormones, change the endometrium into a gland that produces glycogen -If no implantation, you have menstruation again

Functions of testosterone

-Essential for spermatogenesis -Feedback regulation of hypothalamus and anterior pituitary (regulation of LH release). -Development of male organs -Secondary male characteristics -Sex drive -Growth and sealing of the epiphyseal plate -Increased hematocrit (via Erythropoietin) -Increased muscle mass

Glomerular filtration rate (GFR)

-GFR is determined by four factors: capillary hydrostatic pressure (pressure blood exerts against the capillart wall), capillary oncotic pressure (pressure proteins exert in a fluid), fluid oncotic pressure and fluid hydrostatic pressure

Sex determination: SRY gene

-Genotypic Sex -> Male: 46, XY -> Female: 46, XX -Phenotypic Sex -> Development of male or female internal and external genitalia -SRY Gene -> Located on the Y chromosome -> SRY gene stimulates neutral gonadal tissue differentiation into testes. -> Lack of or mutant SRY gene results in the development of female genitalia.

Three Tier System Testosterone and Inhibin

-Gonadotropin-releasing hormone (GnRH) is released from they hypothalamus -> typically in response to low testosterone, 1st step in production of testosterone and spermatogenesis -GnRH, arrives in the anterior pituitary through the hypothalamic portal system and stimulates the release of LH and FSH -> Cells in anterior pituitary have GnRH receptors -LH is released into the bloodstream and stimulates the Leydig cells to produce testosterone. Testosterone diffuses over to Sertoli cells to exert its effects in promoting spermatogenesis. -FSH is released into the blood and stimulates ABP (Androgen binding protein)and inhibin production from Sertoli cells. FSH also stimulates spermatogenesis in the Sertoli cells. -You need BOTH Testosterone & FSH to produce sperm Leydig Cells produce testosterone LH -> Sertoli cells are the site of spermatogenesis -For FSH follow the S's: FSH -> Sertoli Cells -> Spermatogenesis -For LH follow the L's: LH -> Leydig Cells -> MaLe Androgen (Testosterone)

Negative feedback regulation testosterone and inhibin

-Gonadotropin-releasing hormone (GnRH) is released from they hypothalamus. -GnRH, arrives in the anterior pituitary through the hypothalamic portal system and stimulates the release of LH and FSH. -LH is released into the bloodstream and stimulates the Leydig cells to produce testosterone -FSH is released into the blood and stimulates ABP and inhibin production from Sertoli cells. FSH stimulates spermatogenesis in Sertoli cells. -Negative Feedback: Increases in inhibin feeds back negatively to inhibit the release of FSH. -High levels of testosterone feeds back negatively to inhibit both GnRH and LH releas

Sertoli cells

-Help nurture and grow your sperm -Produce substances that protect and promote the development of sperm (spermatogenesis). -Produce androgen binding protein (ABP) and inhibin. -> ABP binds diffusing testosterone to keep levels high in the Sertoli cells enhancing spermatogenesis. -> When sperm production levels are high enough, the Sertoli cells produce inhibin. -> Inhibin feeds back negatively to the anterior pituitary to inhibit FSH (Helps turn off sperm production)

Puberty to maturity

-Hypothalamus of children (prepuberty) is SUPER sensitive (receptor number) to testosterone -> Very low levels of testosterone are more likely to bind to those receptors and shut the system off, in the body there are low levels of testosterone circulating -During puberty—brain becomes less sensitive to testosterone -> Result is that you need more testosterone to shut down the pathway -> Results in increased GnRH, LH, FSH, Testosterone and ABP production More testosterone: -Development of secondary male characteristics -Increased sex drive -Growth and sealing of the epiphyseal plate -Increased hematocrit (via Erythropoietin) -Increased muscle mass

Puberty to maturity

-Hypothalamus of females (prepuberty) is SUPER sensitive to estrogen -During puberty—brain becomes less sensitive to estrogen -> Receptor number goes down, need more hormone to stimulate receptors, body responds by producing more estrogen -Results in increased GnRH, LH, FSH, estrogen, androgens and inhibin. More estrogen... -Development of secondary female characteristics (breasts and genitals) -> Estrogen levels may increase, but not enough to activate the LH spirke and ovulation -Growth of endometrium -Around the age of 12 females will have their first period. -First menstrual periods may be anovulatory. -> Not enough estrogen for ovulation, only proliferation, no differentiation -> They might shed their endometrial lining, but not actually ovulate -Why do you think that is? -> Over time, the follicles will die and the estrogen levels will decrease again, resulting the menses and shedding of endometrium

Negative feedback regulation: Estrogen and inhibin

-Kicked off when estrogen levels are low, signals to hypothalamus that estrogen levels are low and GnRH is released -Gonadotropin-releasing hormone (GnRH) is released from they hypothalamus. -GnRH, arrives in the anterior pituitary through the hypothalamic portal system and stimulates the release of LH and FSH. -LH is released into the bloodstream and stimulates the Theca cells to produce androgens. The androgens diffuse to the GC cells and are converted to estrogen. -FSH is released into the blood and stimulates estrogen production. Once estrogen levels rise, granulosa cells secrete inhibin. -Negative Feedback: Increases in inhibin feeds back negatively to inhibit the release of FSH. -Mid levels of estrogen feeds back negatively to inhibit GnRH, LH and FSH release. -> Prevent estrogen from rising too much

Leydig cells

-LH stimulates testosterone production -> Increased transport of cholesterol into the Leydig cell (Add a few functional groups and you get testosterone) -> Increased transcription of enzymes involved in testosterone production (Process of making new protein that helps with the production of testosterone) -Testosterone diffuses over to Sertoli Cells and stimulates spermatogenesis (paracrine)

Ovaries during pregnancy

-Ovaries release renin during pregnancy 1. Ovaries produce renin (enzyme) 2. Ang II increases aldosteroneproduction. -> Aldosterone increases Na+reabsorption into the blood. 3. Ang II increases vasopressinproduction -> Vasopressin increases H20 reabsorption into the blood. 4. Na+ and H20 reabsorption leads to an increase in blood volume. -Aldosterone causes theinsertion of new Na+ channels and Na+/K+ ATPases in the distal tubule (cytoplasm of cell has lowest concentration of Na+) -Vasopressin causes theinsertion of new water channels (aquaporins) into the collecting duct (lumen of distal nephron has highest concentration of water) -Increase blood volume during pregnancy to meet the increased demand for nutrient, O2 and waste removal due to the growing baby

Pulmonary system during pregnancy

-Pregnancy hormones alter respiratory tegions of the brain leading to increased tidal volume and respiratory rate. -> Get winded very easily -Breathing deeper and more often, leads to an increase in minute ventilation -Since rate of oxygen is constant, over time, oxygen accumulates in the alveoli and oxygen concentration in the alveoli go up, the amount of oxygen that can move into dissolved component changes -End up storing more oxygen in the blood than usual -Increased ventilation, will result in increased alveolar PO2 which will cause more O2 to diffuse into the dissolved component -Increased ventilation, will result in decreased alveolar PCO2 which will cause more CO2 to diffuse into the alveoli out of the dissolved component. -> Remember, the amount of CO2 present in the dissolved component depends on how much is being produced by the cells and how much we are breathing -> Facilitates better transport of CO2 between fetus and mother (Fetus has a little bit higher production of CO2, Facilitates the movement of CO2 from the fetus to the mother, helps to ensure fetus gets rid of CO2) -Remember, pH is intimately dependent on plasma CO2levels. If CO2 levels go up, then plasma H+ goes up (decrease in pH). -> During pregnancy pH increases from from 7.4 to 7.45 consistent with a mild respiratory alkalosis

Cardiovascular system during pregnancy

-Pregnancy hormones are responsible for a dramatic decrease in total peripheral resistance (TPR) at the onset of pregnancy. -Changes in blood pressure are monitored by the baroreceptor reflex arc. -In the pregnant female, the ability to increase TPR goes away so, the reflex arc targets mainly the heart -> Body's ability to control vasodilation and constriction goes away -Increased O2 demand due to the growing fetus requires more blood to be pumped around the body. -Stimulus (disrupts homeostasis by decreasing) -Controlled variable: blood pressure -Receptors: Baroreceptors in carotid sinus and arch of aorta -Input: Stretch less, which decreases rate of action potentials -Control center: CV enter in medulla oblongata -Output: Increased sympathetic decreased parasympthetic stimulation -Effectors: -> Heart: Increased heart rate and contractility lead to increased cardiac output -> Blood vessels: Constriction of arterioles increases total peripheral resistance (TPR) (does not occur during pregnancy) -Response: Increased blood pressure -Return to homeostasis when increased cardiac output and increased total peripheral resistance bring blood pressure back to normal

Milk let down reflex arc

-Progesterone inhibits prolactins ability to have your milk come in -Stimulus: Nursing at the breast -Receptor: Mechanoreceptors -Input: Afferent Nerve -Control Center: Hypothalamus -Output: Oxytocin release from posterior pituitary -Effector: Myoepithelial cells on mammary glands -Response: Contraction and milk ejection -POSITIVE feedback -> Female's body will have multiple let downs through a feeding session. Once the baby is full, it stops nursing and turns this cycle off

Renal system during pregnancy

-Progesterone relaxes afferent arterioles in the kidneys and and increases GFR -Filtration: passing of solutes from the blood into nephron (in glomerulus). -Reabsorption: passing of solutes from the tubule into the capillaries. -Secretion: Passing of solutes from capillaries into the tubule. -Excretion: Passing of solutes to the bladder -Increase in hydrostatic pressure -> Increase in GFR -Decrease in hydrostatic pressure -> Decrease in GFR Amount filtered - amount reabsorbed + amount secreted = amount of solute excreted

Renal clearance

-Renal clearance is a measure of the kidney's ability to clear the plasma of a particular substance over time (ml/min) -Inulin is a molecule that is freely filtered, not secreted and not reabsorbed (Can move from the capillary bed into bowman's capsule just fine, is small enough) -> Inulin's renal clearance is the same as the GFR -Penicillin is a molecule that is freely filtered, partially secreted and not reabsorbed. -> Penicillin's renal clearance is greater than the GFR. -Urea is a molecule that is freely filtered, not secreted and partially reabsorbed -> Clearance of urea is less than GFR -Clearance of certain drugs will be higher during pregnancy. Therefore, patients may have to take an increased dose. (ex: lithium)

Why are the lungs the last organ to develop in utero?

-The baby is not reliant on the lungs -The umbilical cord delivers O2 to the baby throughout pregnancy -High levels of oxygen can be harmful for the lung -Surfacant isn't always produced in a baby that is born premature

Differentiation: Development of the fetus & placenta

-Week 9 -The interface between the chorionic villi and the mother's blood supply are where exchange of nutrients and gases occurs -Maternal to fetal -> O2, nutrients, hormones, antibodies and drugs -Fetal to maternal -> CO2, metabolic waste, hormones -Arteries: Carrying deoxygenated blood away from heart of fetus, getting rid of waste products, and putting them into the mother's blood supply -Placenta: The only organ a human body grows that is short term -Vein: Carrying blood that is oxygenated towards the fetus -Blood vessels, meeting up with blood supply from mother Important that baby's blood and mother's blood do NOT mix

Female Reproductive Cycle: Ovulation

1. High levels of estrogen from the developing granulosa cells stimulates the release of GnRH 2. Increased GnRH results in a surge of primarily LH but also FSH from the anterior pituitary -> LH is preferred 3. The increase in LH in response to high levels of estrogen is termed the LH spike -> Follice itself determines when it's ready to be ovulated 4. The high levels of LH stimulates the release of the egg (ovulation) -> Rest of the follicle stays behind and forms the corpus luteum ***The follicle determines when ovulation occurs. Once it is capable of producing enough estrogen it stimulates its own ovulation! -Ovulation marks the end of the follicular phase and beginning of the luteal phase

Female Reproductive Cycle: Follicular Phase

1. Low levels of estrogen stimulates the release of GnRH from the hypothalamus. 2. GnRH activates the release of LH and FSH from the anterior pituitary. 3. LH goes to the theca cells to stimulate androgen production 4. FSH accumulates in the antrum and stimulates estrogen production in the GC. (The dominant follicle will accumulate the most FSH and is the most sensitive of all follicles) 5. Granulosa cells take up androgens and produce estrogen 6. Estrogen from the follicle stimulates -> Endometrial growth and proliferation -> Mid range levels inhibits the hypothalamic production of GnRH, LH and FSH -> High levels activates release of GnRH. -> Once the granulosa cells expand enough, they produce the signal through estrogen production, high levels of estrogen now activate the hypothalamus and the anterior pituitary 7. Even with low GnRH, LH and FSH, the local levels (in the follicle) of estrogen continue to rise do the accumulation of FSH in the antrum of the dominant follicle. Estrogen from the granulosa cells continue to rise until the LH spike is initiated.

Female Reproductive Cycle: Luteal phase

1. The ruptured follicle turns into a hormone secreting organ called the corpus luteum. 2. The corpus luteum is the primary hormone producing structure at this point. It secretes high levels of progesterone and some estrogen. 3. Progesterone promotes differentiation of the endometrium converting it to a gland capable of producing nourishing substances for a potential fertilized egg (Secretory Phase). Progesterone is feeds back negatively to feedback Tier 1 and Tier 2. -> Low progesterone can underlie some infertility, 4. Estrogen helps with the growth and maintenance of the endometrium. 5. If pregnancy occurs: the corpus luteum will stay alive and continues to produce hormones until the placenta can take over. 6. If pregnancy does not occur: the corpus luteum dies and forms the corpus albicans. It no longer produces hormones so the endometrium sheds (menses).

Hormone fluctuations during pregnancy: HCG, Estrogen, & Progesterone

Estrogen: -Produced by placenta. -During pregnancy its main effects: -> Endometrial proliferation -> Increase oxytocin receptor number in uterus. Progesterone: -High levels of progesterone inhibit menses -Need a muscle cell to contract, need it to depolarize, more potassium leaves the cell, membrane potential begins to fall, need stronger stimulus to reach depolarization threshold -Produced by placenta -During early pregnancy: -> Promotes differentiation and granular secretion of uterus -> Keeps myometrium quiescent (increased K+ channel expression) -> Inhibits prolactin's effects (inhibiting milk production) Human chorionic gonadotropin (HCG): (Hormone being tested on test strip) -Produced by the blastocyst -Binds to the LH receptor on the corpus luteum increasing the production of progesterone -Known as the pregnancy hormone. -> Its levels increase within the first month of pregnancy -Mother also delivers placenta, the source of all these hormones, so your hormone levels crash after delivery Perfect storm for people to be pushed into postpartum depression (hormone crash along with lack of sleep, with breast feeding and more)

Ovarian events

Follicular phase -Developing a set of follicles, one of these follicles will eventually rupture and release the egg out into the space where it can be picked up by the fallopian tube -> Start with a handful and one eventually becomes selected, typically the one that produces the most estrogen and has the highest number of FSH and LH receptors -If ovary need to communicate with uterus it needs to rely on bloodstream and hormones, as they are too fat apart for diffusion to be effective Ovulation -When the follicle ruptures and the egg is released -When egg is released, it is released with a small ring of cells around the top, vast majority of the structure stays behind in the ovary Luteal phase -The egg has left and needs to make its way into the fallopian tube -The granulosa cells and theca cell form another gland called the corpus luteum, its main job is to secrete hormones (they go to the uterus) and thicken the uterus , make sure there's enough sugar there, in case implantation happens

Male anatomy: Making semen

General Information -Semen: Composed of sperm cells and seminal plasma -> Seminal plasma comes from accessory structures, lots of ducts and gland that deliver into the semen -Primary Structures: Structures that produce gametes (testes). -Accessory Structures: Organs, ducts, and glands that deliver the gametes to the outside environment. -> ~90% of semen comes from the accessory organs. -Ejaculation: process of moving semen through the reproductive tract. Specifics -Epididymis: Sperm develop & mature here over a two week period. -Seminal vesicle: make up the bulk of the seminal volume. Secretions contain the following: -> Sperm need to make lots of ATP for swimming -> Citric acid: Used by sperm to make ATP -> Clotting enzymes: clots semen after ejaculation (protective, neutralize environment for sperm) -> HCO3 (protective) -> Proteolytic enzymes: break down the clot. • Seminal plasmin (antibiotic)

Development of embryo: Implantation and gastrulation

Implantation: -Covering of the entire embryo in cells -Endometrium is rich in glycogen and blood vessels due to Progesterone. -Blastocyst secretes HCG, starts breaking down wall of uterus -Release of proteolytic enzymes to breaks down uterine wall to gain access to the blood source. -Eventually the entire blastocyst will be covered by the uterine wall -> In order for it to survive, it as to reach a blood supply Gastrulation: -The process by which the three germ layers differentiate is called gastrulation. -Endoderm becomes lining of the GI -Ectoderm becomes skin and nervous system. -Mesoderm becomes muscle, bones and connective tissue.

Three stages of labor

Stage 1: Dilation of the cervix -Uterus must dilate to 10cm. Prostaglandins help soften the cervix -Lasts 6-12 hours -Contractions and rupture of the amniotic sac likely Stage 2: Expulsion of the baby -Increased oxytocin release stimulates strong uterine contractions (active labor) -Last 10 mins to hours -Ends when baby is born Stage 3: Placental delivery -Blood vessel constriction important to prevent hemorrhage -Shortest stage lasting 5-30 minutes -Aided by nursing baby ->Nursing will increase oxytocin release and will therefore increase uterine contractions to help push out the baby