Reproduction 2 Flashcards
The ovaries contain millions of ___ follicles with ovum arrested in meiosis I at birth and consist of the ___ and ___.
Ovarian follicles are in the ___.
Major blood vessels and nerves reside in ___.
(copy qn and fill in the blanks)
The ovaries contain millions of primordial follicles with ovum arrested in meiosis I at birth and consist of the cortex and medulla.
Ovarian follicles are in the cortex.
Major blood vessels and nerves reside in medulla.
The ovarian follicles consist of ___, surrounding ___ cells and ___.
Follicular cells include ___ (surrounds the ovum) and ___ cells (counterpart of Leydig cells in males)
- Works together to produce ___
- ___ cells (similar to Sertoli cells in males) produce ___ ___ to cover the oocyte.
- ___ cells are specialized connective tissue cells
After puberty, some follicles develop each month.
(mature follicles are also called Graafian follicles)
(Zona pellucida supports communication between oocytes and follicle cells)
(copy qn and fill in the blanks)
The ovarian follicles consist of oocytes, surrounding follicular cells and stroma.
Follicular cells include granulosa (surrounds the ovum) and thecal cells (counterpart of Leydig cells in males)
- Works together to produce estrogen
- Granulosa cells (similar to Sertoli cells in males) produce Zona pellucida to cover the oocyte.
- Thecal cells are specialized connective tissue cells
After puberty, some follicles develop each month.
(mature follicles are also called Graafian follicles)
(Zona pellucida supports communication between oocytes and follicle cells)
How is estrogen synthesis in ovarian follicles?
Luteinizing hormone stimulates the thecal cells, which allows cholesterol to enter and convert to androgen, which diffuses into granulosa cells, which is stimulated by the Follicle-Stimulating Hormone, converting androgen to estrogen.
Estrogen at high concentration then sends a negative feedback signal to the granulosa cells, regulating estrogen production.
Estrogen then contributes to antral formation and is secreted into blood.
When does menstrual cycle occur, its cycle length, its feature, and the 2 cyclic changes involved.
Menstrual cycle occurs during female reproductive period (from puberty to menopause)
The cycle lengths vary and average around 28 days and its most conspicuous feature is vaginal bleeding.
Each menstrual cycle involves two cyclic changes, ovarian cycle (driven by hormones) and uterine cycle.
Describe the 3 phases of the ovarian cycle
Follicular cycle (day 1-13)
- Maturation of the oocyte and proliferation of granulosa and thecal cells
Ovulation (day 14)
- Enlarged graafian follicle bulge on the surface of the ovary and release the mature oocyte
Luteal phase (day 15-28)
- After releasing oocytes, follicular cells are converted into steroidogenic cells that form the corpus luteum (contains large amount of cholesterol and lipid ⇒ yellow body appearance)
- Secretion of large quantity of progesterone and moderate amount of estrogen to prepare the uterus for embryo implantation
The effects of raising levels of estrogen, peak of estrogen level, and the effect of corpus luteum producing estrogen and progesterone.
- Raising levels of estrogen exerts a negative feedback to the Follicle-Stimulating Hormone, ensuring that the FSH level does not rise and some limited inhibition on Luteinizing Hormone.
- At the peak of estrogen levels, a positive feedback is exerted on LH release, causing the sudden/abrupt LH surge which targets the ovarian follicle which results in the release of the ovum (ovulation)
- As the corpus luteum produces progesterone and estrogen, a negative feedback is exerted on the LH level, decreasing the LH and FSH levels.
The LH maintains the corpus luteum/steroidogenic cell’s status and a fall in LH levels will lead to the regression of the corpus luteum, resulting in a fall of progesterone and estrogen, which exerts a negative feedback on the anterior pituitary, stimulating the release of LH and FSH, which leads to the start of a new ovarian cycle.
Hormonal regulation in follicular phase
Both LH and FSH stimulate estrogen synthesis
Estrogen and FSH stimulates the granulosa cells proliferation and follicles maturation (via negative feedback)
Moderate levels of estrogen exert negative feedback to inhibit FSH and LH secretion, but the FSH-producing cells are more sensitive to estrogen
Hormonal regulation during ovulation
High concentrations of estrogen exerts positive feedback to cause an abrupt rise in LH secretion (LH surge)
LH surge trigger ovulation by inducing local production of prostaglandin and activation of proteases (plasmin) through progesterone receptors
Describe how progesterone and prostaglandins modulate proteolytic activity during ovulation
Prostaglandins dilate blood vessels, increasing permeability of blood vessels and increasing the content of proteolytic inhibitors.
Progesterone increases the expression and production of progesterone receptors, increasing proteolytic activity that digest walls of follicle and thecal cells
The effect of PR gene deletion on granulosa cells
Accumulation of mature ovarian follicles due to the lack of progesterone receptors, resulting in the failure of the apex to rupture and ovulation cannot occur
Describe the process that allows ovulation to rupture
To allow ovulation to rupture, follicle cell must rupture, and protease is required to digest the thecal cell and granulosa cells. Thus, the LH surge leads to increased progesterone receptors, increasing progesterone, increasing proteolytic enzymes to digest
To prevent over-digestion: Secrete protease inhibitor stimulated by prostaglandin
- LH surge leads to an increase in production and expression of COX II, which increases prostaglandin production (prostaglandin Es and prostacyclin), leading to vasodilation, increasing blood flow which then increases proteolytic inhibitors, decreasing proteolytic activity.
Hormonal regulation in luteal phase
LH triggers the differentiation of follicular cells into luteal cells and stimulate the secretion of large amount of progesterone and moderate amount of estrogen.
The rising levels of progesterone and estrogen exerts a negative feedback on LH and FSH secretion ⇒ decrease LH and FSH concentration ⇒ demise of corpus luteum as LH maintains the corpus luteum
The fall of estrogen and progesterone following the demise of corpus luteum results in the negative feedback on the anterior pituitary, increasing the secretion of LH and FSH that initiates the next follicular phase
Mechanism of negative and positive feedback on GnRH secretion by estrogen (Both high levels and moderate levels of estrogen)
High level of estrogen:
- Estrogen targets Kiss-1 neurons, specifically the Anteroventral Periventricular (AVPV) via positive feedback
- AVPV stimulated, increasing the production of kisspeptin
- Results in positive feedback on the GnRH neurons, increasing GnRH secretion
- GnRH then stimulates the pituitary glands to increase secretion of LH and FSH
Moderate levels of estrogen:
- Estrogen targets Kiss-1 neurons, specifically the arcuate via negative feedback
- Increases production of kisspeptin (inhibit)
- Results in negative feedback to GnRH neurons which decreases GnRH secretions
- The low GnRH secretion then cannot stimulate the pituitary gland to secrete the LH and FSH
- Estrogen affects the GnRH secretion, not kisspeptin proteins!!
Historical structure of the uterus
- Endometrium: stratified epithelium, stroma, glands
- Myometrium: smooth muscle
- Perimetrium: connective tissue covered by simple squamous epithelium
Describe the uterine cycle (coincides with the ovarian cycle)
Proliferative phase (endometrium proliferation, corresponds to the follicular phase) (day 1-13):
- Estrogen stimulates the growth of epithelial cells, glands, and blood vessels
Secretory phase (corresponds to the luteal phase) (day 15-28):
- Progesterone converts the thickened endometrium into highly vascularized, glycogen-filled tissues which provides nutrients to incoming embryo (if any)
Menstrual phase (coincides with the end of luteal phase and onset of follicular phase):
- Characterized by necrosis and sloughing of the endometrium due to the demise of the corpus luteum
- In the absence of the estrogen and progesterone, endometrium blood vessels increase in prostaglandin concentration
⇒ leads to an increase in blood vessel constriction, decreasing nutrients and O2 supply to tissue and breaking of smaller blood vessels/capillaries
What is the uterine cycle driven by?
The ovarian cycle due to the changing levels of estrogen and progesterone.
Causes of the disruption of the menstrual cycle
Abnormalities in the Hypothalamus-Pituitary- Ovary axis, stress (affects the hypothalamus), low body weight (sends signals to the brain that the body is not ready to receive embryo/prep for pregnancy ⇒ halt all prep for pregnancy)
Types of menstrual cycle disruption, risks, and benefits
Amenorrhea: absence of menstruation
Oligomenorrhea: irregular cycle/infrequent intervals
Menopause: cessation of menstrual cycle at the end of the reproductive age of women (either by brain exhaustion or by complete exhaustion of the ovarian follicles)
Risks: premature osteoporosis
Benefit: lower cancer risks in reproductive tissue
Oral contraceptives (what it does, types of contraceptives, and its effect)
- Inhibit ovulation
- Inhibit fertilization (prevent the sperms from reaching the fallopian tube)
- Prevent implantation
Types:
- The ‘pill’ → synthetic estrogen and progesterone
- The ‘minipill’ → synthetic progesterone (lactating women cannot/do not take estrogen)
- Plan B & Ella → morning after pill
- Hormonal termination of pregnancy
- RU486/prostaglandin (Mifepristone/Misoprostol) → act as progesterone receptor antagonist, but has not well-established side effects
Effect: increased blood clotting, cancer risks
Where does fertilization occur in?
The ampulla, a dilated part of the ovarian tube
- The sperms travel ∽20cm from the vaginal opening while the egg remains in the ampulla
- Of about 300 million sperms ejaculated, only ∽100 reach the fallopian tube and usually one fertilizes the egg
How does the sperm fuse with the egg?
Hyaluronidase and acrosin from the acrosome of the sperm digests the corona radiata and zona pellucida, allowing sperm to fuse with the ovum cell membrane
- After the sperm fuses with the ovum, Na+ rushes into the ovum and changes the membrane potential and blocks the ovum from being penetrated by other sperms
Implantation, how it occurs and when
- The zygote divides as it travels from the ampulla to the uterus via the oviduct
- Around 6 days after fertilization, blastocyst (a hollow ball of ∽100 cells) attaches to the uterine wall (implantation)
- The trophoblastic cells develop into the fetal portion of the placenta (tries to form a clot of cells to dig deep into the endometrium for implantation) and inner cell mass differentiates into fetus
How does Human Chorionic Gonadotropin (HCG) maintain the corpus luteum in the 1st trimester?
Trophoblast cells secrete HCG after implantation
- HCG exerts LH like effects on corpus luteum
- HCG binds to the LH receptors on corpus luteum
- HCG maintains the function of corpus luteum: to secrete progesterone and estrogen to maintain the uterine lining for the zygote
* Presence of HCG in urine is the basis for home based pregnancy test kits
Mechanism of labor
- The placenta increases the secretion of cortisol-releasing hormone into fetal circulation, which then increases ACTH from fetal adrenal cortex
- Fetal adrenal cortex then leads to the increase in secretion of cortisol which helps in the maturation of fetal lungs, stimulating the increase in secretion of the pulmonary surfactant, leading to lung maturation.
- Fetal adrenal cortex then stimulates the increase in secretion of the dehydroepiandrosterone (DHEA) which in turn stimulates the placenta to convert DHEA to estrogen, producing estrogen. - Increased pulmonary surfactant in amniotic fluid increases the macrophages in the uterus, leading to an increase in IL-1β, which along with the uterine stretching, activates the NF-kB in uterus, which helps in prostaglandin production and helps in cervical softening. NF-kB also leads to an increase in IL-8, which increases oxytocin receptor.
- Increased gap junction formation is stimulated by estrogen (allows ion to pass through to transmit signals to muscle cells to work as a unit and allow the uterus to contract as a coordinated unit). This helps in increasing uterine sensitivity to low oxytocin
- Estrogen, prostaglandin and IL-8 increase the amount of oxytocin receptors, increasing uterine sensitivity to low oxytocin
- The increase in uterine sensitivity to oxytocin leads to an increase in uterine contractions, pushing the fetus against the cervix via the neuroendocrine reflex, which leads to oxytocin secretion and hence prostaglandin production. Oxytocin and prostaglandin then leads to an increase in uterine contractions.
Name the placenta hormones (got 5)
- Human Chorionic Gonadotropin
- Estrogen (estriol is the main form)
- Progesterone
- Placenta lactogen (Human Chorionic Somatomammotropin)
- Corticotropin-Release hormone
Types of estrogen (got 3) and its functions (got 5)
Estradiol: produced by the ovaries
Estrone: produced in the adrenal glands/adipose tissue
Estriol: produced by uterus during pregnancy
- Estrogen stimulates endometrial growth and uterus enlargement (thickening of the uterine lining in anticipation of possible pregnancy)
- Inhibits prolactin secretion
- Stimulates the growth of mammary ducts
- Supports bone health
- Supports cardiovascular health
Function of progesterone (got 5)
- Inhibits estrogen induced endometrial growth
- Suppresses uterine contractions
- Stimulates gland secretion and decidualization (a process that results in significant changes to the cells in the endometrium in prep for pregnancy)
- Promotes the formation of mucus plug in the cervix
- Stimulates the development of mammary alveoli
Placenta lactogen is a natural growth hormone during pregnancy, what are the properties of the placenta lactogen (got 4)
- The amount of placental lactogen secreted is proportional to the size of the placenta ⇒ normally 1/6 of the fetus
- Structurally similar to growth hormone and prolactin
- Metabolic effect in mother; lipolysis and decrease in glucose utilization to aid in the diversion of glucose to fetus
- Prepare the mammary gland for lactation after birth
Structure of the mammary gland (got 4)
- Consists of mammary ducts and alveoli
- Alveolus is the functional (secretory) unit of the breast
- Clusters of alveoli are organized into lobules
- Groups of lobules form larger clusters of lobes
Mammary gland development in rats and mice
- Rudimentary (undeveloped/not matured) mammary ducts are present at birth
- The mammary development is limited to mammary ducts and buds before puberty (and some alveoli in matured animals)
- Extensive ductal and alveoli development during pregnancy
- After weaning, the mammary glands undergo involution (shrinkage) during which many mammary cells undergo apoptosis, which overtime the size and number will increase during pregnancy and decrease after weaning
Regulation of the mammary development by estrogen and progesterone receptors
- ERα-mediated estrogen action is essential for ductal morphogenesis (extensive growth)
⇒ ERβ is not involved in the mammary development
-PR-mediated progesterone action is required for ductal branching and alveoli development
Hormones required to develope mammary glands to secrete milk
- Atrophic duct to duct growth:
Estrogen + growth hormone + adrenal steroids - Duct growth to lobulo-alveolar growth
Estrogen + growth hormone + adrenal steroids + progesterone + prolactin - Lobulo-alveolar growth to milk secretion:
Prolactin + adrenal steroids
- Without hormones, mammary glands will undergo atrophy
Hormonal regulation of mammary development during pregnancy and lactation
- Placenta secretes estrogen, progesterone, and placenta lactogen which leads to the growth and development of glands and ducts (placenta lactogen functions similarly to prolactin but does not have the same extent of effect as prolactin and thus, cannot stimulate full lactation)
- Estrogen also stimulates the hypothalamus to release prolactin inhibitory hormones which inhibits prolactin release from the anterior pituitary (prevents premature lactation).
- When prolactin is secreted by anterior pituitary, prolactin and glucocorticoid stimulates milk production in the mammary glands - Insulin (secreted by pancreas), cortisol (secreted by adrenal cortex), and thyroxine (secreted by thyroid) are important metabolic hormones that have permissive effects towards the growth and development of glands and ducts
Describe the 3 stages of lactation
Lactogenesis I: cytological and enzymatic differentiation of alveolar cells before parturition (birthing)
- Dramatic hypertrophy of the RER and the Golgi, increasing the no. of mitochondria
- Increase in enzymes for milk synthesis
- Limited milk synthesis and secretion
Lactogenesis II: onset of copious milk secretion
- Occurs in women at 1-2 days post partum ⇒ induced by newborn suckling at nipple
Lactogenesis III: maintenance of milk secretion
Milk synthesis
Lactose synthesis:
- Galactosyltransferase and α-Lactalbumin
Lactose synthesis is then used in the conversion from UDP-galactose + glucose to lactose + UDP
Lactose, milk protein, salts, and water are packaged into secretory vesicles which are discharged into the alveolar lumen to produce milk!
Casein is used for casein micelle formation
β-Lactoglobulin is α-Lactoglobulin in humans
What is the suckling reflex and maintenance of lactation?
Suckling triggers the mechanoreceptors in nipples, which sends nerve impulses to the hypothalamus, leading to 2 pathways:
- The nerve impulse travels to the nervous pathway which stimulates the posterior pituitary, increasing oxytocin secretion, which increases the contraction of myoepithelial cells surrounding the alveoli, leading to milk ejection.
- The hypothalamus decreases the secretion of prolactin-inhibiting hormone and increase the secretion of prolactin-releasing hormone, stimulating the anterior pituitary to increase prolactin secretion, leading to an increase in milk secretion.
