Skafar Flashcards
What are the different parts of the female reproductive tract? what is each of their functions?
- Ovaries: development of gametes and secretion of hormones (estrogen, progesterone, inhibin)
- Oviduct: transport of oocyte to uterus
- Uterus: myometrium and endometrium; provides environment for development of zygote into fetus
- Cervix: strong boundary between uterus and vagina
- Vagina: birth canal
How does oocyte development occur?
Oocyte starts to develop prior to birth, but arrested at the first division of meiosis
- First meiotic division not completed until just prior to ovulation
- Second meiotic division completed after fertilization
How does follicular development in the female reproductive system occur? What are the stages of follicular development during the menstrual cycle?
At birth, a female has 2-4 million of these primordial follicles (simplest type- oocyte with single layer of granulosa cells)
A woman will only ovulate a few hundred of these in her lifetime
Development occurs during the menstrual cycle • Oocyte increases in size • Granulosa cells proliferate • Theca cells appear • Antrum (fluid-filled space) develops
Ovulation: release of oocyte and some of its surrounding granulose cells from the follicle
• Remaining granulosa cells and theca cells then form the corpus luteum, which regresses after 2 weeks if pregnancy does not occur
During menstrual cycle:
All of these processes in all 3 stages depend on LH, FSH, estrogen, androgens (precursors for estrogens) and progesterone
1. Follicular Phase: from primordial follicle to pre-ovulatory stage (14 days)
2. Ovulation: takes less than one day
3. Luteal Phase: corpus luteum functioning (14 days)
What is the function of the different hormones in follicular development?
- FSH: acts on granulosa cells causing them to secrete estradiol (require androgen precursors from theca)
• Combination of FSH and estradiol cause granulosa cells to proliferate
• Increasing the number of cells increases the production of estradiol - LH:
• In the early follicle (before antrum development) only the theca and stroma cells have receptors for LH
-Theca cells supply granulosa cells with androgen precursors for estradiol synthesis under the influence of LH
• In the pre-ovulatory follicle, granulosa cells also have LH receptors
- Development of receptors accompanied by production of progesterone and a decreased amount of aromatase, resulting in a drop in the level of estrogen and a slight increase in progesterone
- The signal for ovulation is an LH surge
- Also requires progesterone receptor and progesterone
- Prostaglandins and plasminogen activator may also play a role
• LH initiates formation of corpus luteum
• LH required for continued steroid production
What are the two types of estrogens?
- Estradiol: can be synthesized from testosterone via the enzyme aromatase
- Circulates at extremely low levels (can vary 20 fold at different points in the menstrual cycle)
- Circulates bound to either albumin or SHBG (very little is in free form) - Estrone
** Estrogens are inactivated in the liver by conjugation with sulfate or glucoronide and then excreted by the kidneys
What hormones are produced by the ovaries? what are their activity level/where are they produced? ?
- Estrogens: from testosterone, circulates bound to albumin of SHBG
- Progesterone: produced mainly by corpus luteum (some from granulosa cells just prior to ovulation); most is bound to CBG in circulation; Progesterone is inactivated in the liver by conversion into pregnanediol, and then excreted by the kidney
- Peptide hormones:
Inhibin (produced by granulosa cells; after ovulation they are produced by the corpus luteum)
Relaxin
What are the different stages involved in the menstrual cycle?
- Menstrual Phase (Day 1-5; also part of Follicular Phase of Ovarian Cycle):
- Uterine endometrium being shed
- Estrogen and progesterone levels are low
- LH and FSH levels are low (but start to increase at start of menses due to low levels of estrogen and progesterone, which decreases negative feedback)
- Several follicles begin to develop in the ovary and secrete estrogen - Proliferative Phase (Follicular Phase of Ovarian Cycle):
Day 6-10:
- Ovarian follicles continue to develop and secrete estrogen (estrogen levels rising)
- Theca cells begin to develop and produce androgens (provide to granulosa cells; estrogen production increases further)
- Progesterone remains low
- LH stays constant
- FSH levels start to decrease
- One follicle is selected to continue development (day 7) and the rest degenerate
- Uterine endometrium proliferates and thickens
Day 11-13:
- Plasma estrogen levels increase and remain elevated; Increasing estrogen levels causes the frequency of GnRH pulses to increase
- LH and FSH levels begin to rise
- Granulosa cells develop receptors to LH (prior to ovulation), and due to LH stimulation, begin to luteinize; Decrease estrogen production, increase progesterone production
- Uterine endometrium continues to proliferate and thicken
Ovulation (Day 14):
- Increased estrogen for at least 36 hours causes positive feedback on gonadotropin secretion and leads to LH surge
- Oocyte finishes its first meiotic division and is ovulated 9-16 hours after the surge
- Secretory Phase (Luteal Phase of Ovarian Cycle):
Day 15-25:
- LH and FSH levels drop rapidly
- Corpus luteum secretes progesterone and estrogen
- Frequency of GnRH pulses decreases
- Endometrium becomes highly vascularized and slightly edematous
- Glands become coiled and secrete a clear fluid
Day 26-28:
- LH and FSH levels continue to decline
- If pregnancy hasn’t occurred, produced of estrogen and progesterone from corpus luteum declines
- Corpus luteum degenerates and estrogen and progesterone levels are very low
- Leads to shedding of uterine endometrium and start of new cycle
What is estrogen/ progesterone’s mode of action?
bind proteins located in cells, which then alter transcription and translation of proteins produced in that cell
What are the concentrations of hormones produced by the ovaries?
- Estradiol:
Low in early follicular phase (50 pg/mL), but affinity for receptor is high (“enveloped” by it)
Pre-ovulatory: 200-250 pg/mL
Luteal phase: 100 pg/mL
- Progesterone:
• Follicular Phase: 0.9 ng/mL
• Mid-Luteal: 18 ng/mL
What are some of the effects of estrogen?
1. Internal Genitalia: • Growth of ovarian follicles • Increased motility of uterine tubes • Increased proliferation of uterine myometrium and endometrium (storage of nutrients as well) • Increased contractility of uterus
- Breasts: increase proliferation of ducts
- Cervix: thinner, more alkaline mucus (fern pattern when dried)
- Vagina: cornified epithelium
- Bone: epiphyseal closure
- Skin: thins sebaceous gland secretions
- CV: lower plasma cholesterol and inhibit atherogenesis
- Fat: distributed to breasts and buttocks
- Psychological: increased libido
- Other:
• Increased angiotensinogen
• Increased TBG
• Salt, water retention
• Increases synthesis of progesterone receptor
**Therefore, vast majority of progesterone effects are in concert with estrogen
What are some of the effects of progesterone?
*in combination with estrogen
1. Internal Genitalia:
• Inhibits myometrium contractility (decrease electrical activity and sensitivity to oxytocin)
• Endometrium more highly vascularized and edematous
• Uterine glands coiled and begin to secrete
• Increases membrane potential
• Increases metabolism of estradiol to less active forms of estrogen
- Breasts: increased growth of lobules and alveoli
- Basal Body Temperature: slight increase
- Cervix: thicker, more cellular mucus (no fern pattern)
- Vagina: thicker mucus, epithelium proliferates
- Respiration: decreases pCO2 (increases respiration)
- Kidney: produce natriuresis (block aldosterone?)
Describe the hormone levels of LH and its regulation during the menstrual cycle
- Low and increase slightly at the beginning of the cycle
- Stay relatively constant until late follicular phase when LH surge occurs
- After LH surge, levels drop rapidly and continue to decrease during luteal phase
Describe the hormone levels of FSH and its regulation during the menstrual cycle
- Low and increase slightly at the beginning of the cycle
- Remain constant until middle of follicular phase, slightly decrease as ovulation approaches
- Small peak coincident with LH surge prior to ovulation
- Levels continue to decrease during luteal phase of cycle
Describe the hormone levels of estrogen and its regulation during the menstrual cycle
- Low at the beginning of the cycle
- Gradually increase in middle of follicular phase
- Rate of increase increases further, and estradiol levels very high for ~2 days (reach a maximum 2 hours before LH surge)
- Levels fall at ovulation
- Second increase during luteal phase (produced by corpus luteum)
- Levels fall as corpus luteum degenerates
Describe the hormone levels of progesterone and its regulation during the menstrual cycle
- Very low in first part of cycle
- Rise as LH increases
- Continue to rise during luteal phase (produced by corpus luteum)
- Levels fall as corpus luteum degenerates
Describe the feedback regulation of LH and FSH secretion
- Negative Feedback:
o Low doses estradiol (decreases GnRH and LH)
o Estrogen + progesterone (decreases GnRH and LH)
o Inhibin (decreases FSH) - Positive Feedback:
o High estrogen for ~36 hours (increases GnRH and LH)
Describe the neural control of hormone secretion in the female reproductive system (what things increase/decrease GnRH pulse frequency
- Increase GnRH Pulse Frequency:
o NE
o Estrogen (every 60 minutes near time of ovulation)
2. Decrease GnRH Pulse Frequency: o Enkephalins and beta-endorphin o Progesterone (therefore, pulses less frequent in luteal phase than in follicular phase)
Describe the differentiation of the Male reproductive system (in utero)
In the absence of signals, development proceeds as female; Up until week 6 of gestation the gonad is indifferent with a cortex and medulla
In the male, the cortex regresses and the medulla expands to form the embryonic testes
**Opposite in the female (cortex expands, medulla regresses)
SRY/TDF: located on the end of the short arm of the Y chromosome
o Gene encodes transcription factor that causes male development
Process:
o 44XY acts on bipotential gonad to stimulate SRY production
o SRY stimulates the testes to produce 2 hormones
1. Mullerian Inhibitory Substance (MIS): inhibits female internal genitalia
2. Testosterone: responsible for internal and external male genitalia, as well as the “male brain” (masculinized in the release of GnRH- remains the same everyday)
Testicular Descent:
o Movement of testis to inguinal canal (pulled by gubernaculum), herniation of the abdominal wall, and descent of testes into scrotum
o May or may not occur prior to birth (may have to perform surgery if they do not descend soon after being born)
o Importance of descent:
• Undescended testicles have higher risk for cancer development
• Undescended testicles are at a higher temperature which can lead to infertility
Describe the Jost Experiments
- Male Castrated Early: female duct system (must be something in the testes that causes formation of male duct system and regression of female duct system)
- Female Castrated Early: female duct system
- Male Unilaterally Castrated Early: female duct on castrated side, male duct on side with remaining testis
- Male Castrated Early plus Testosterone: both male and female ducts (therefore, testosterone causes the formation of male ducts but not the regression of female ducts)
- Testosterone Treated Female: both ducts
What organs are involved in sperm transport? what is each of their specific function?
- Epididymis: required for transport and maturation
• Acquire motility
• Become concentrated (important in fertility)
➢ 100 million/mL is the average
➢ 20-50 million/mL results in impaired fertility
➢ <20 million/mL results in infertility - Vas Deferens: sperm transport and storage
- Penis: brings sperm to female reproductive tract
What is the function of the testes?
- Gametogenic: produces sperm
2. Endocrine: synthesizes and secretes hormones for male development
What is the function of the glands in the male reproductive system? (each gland specifically)
OVERALL: Secrete components of semen:
1. Prostate gland: contribute 20% of total volume of semen; Spermine, citric acid, cholesterol, phospholipids, fibrinolysin, fibrinogenase, zinc, acid phosphatase
- Seminal vesicles: contributes 50% of volume of semen; Fructose, phosphorylcholine, ergothioneine, ascorbic acid, flavins, prostaglandins
- Bulbourethral (Cowper’s) Glands
*****Other components not listed above: buffers (phosphate and bicarbonate), hyaluronidase (degradative enzyme)
What is the function of the Sertoli cells? How do they interact with sperm?
Function of Sertoli Cells:
- Regulate sperm development
- Form blood-testes barrier
- Secreted fluid in seminiferous tubules (propels sperm)
- Secrete androgen-binding protein (ABP; keeps androgens in Sertoli cell- needed for gamete production)
- Synthesize and secrete inhibin
- Produce MIS (important in utero, but not clear if it functions at all after birth)
Interaction with Developing Sperm:
Sperm are surrounded by but not enclosed within Sertoli cells; Sertoli cells are connected by tight junctions, which the developing sperm move through and then develop into secondary spermatocytes
Describe the process of spermatogenesis
Spermatogonia (46,2) undergo mitosis → Primary Spermatocyte (46,2) which undergoes first meiotic division with equal division of cytoplasm → Secondary Spermatocyte (23,2) which undergoes the 2nd meiotic division with equal division of cytoplasm → Spermatid (23,1) which finally undergoes differentiation to become a mature spermatozoa (23,1)
Primary spermatocytes stay connected to one another by junctions between spermatocytes until the final stages of differentiation:
Connection of cytoplasm allows for coordination in production
What are the different structural parts of the sperm and what do they contain?
- Head: contains mostly DNA
- Acrosome: contains digestive enzymes, essential for fertility
- Mitochondria: wrapped around flagellum to provide energy for motility
- Tail: propels the sperm
What is the function of Leydig cells?
- **Synthesize and secrete testosterone:
- Produces more than 95% of testosterone in males
Two crucial steps in synthesis:
- Cholesterol converted to pregnenolone
- Cleavage of side chain at C-1
Describe the biosynthesis of testosterone
- Cholesterol → Pregnenolone using side chain cleavage enzyme (mitochondria)
- Pregnenolone → 17α-hydroxypregnenolone using 17α-hydroxylase (SER)
- 17α-hydroxypregnenolone → DHEA → Androstenedione or Androstenediol
- Both can be converted to testosterone
Describe the interaction between Leydig cells and Sertoli cells:
= 2 Cell 2 Gonadotropin Hypothesis:
1. Leydig cell:
Stimulated by LH to increase testosterone production and secretion; Activates PKA pathway that causes synthesis of enzymes involved in testosterone production; Most of the testosterone enters a neighboring Sertoli cell (needed for gamete production); Some enters the blood stream
- Sertoli cell:
Stimulated by FSH to synthesize proteins:
• Inhibin
• ABP (keeps androgens in Sertoli cell- needed for gamete production)
• Aromatase (converse testosterone to estradiol, which is also necessary for male fertility)
