Reproductive system

Question 1

What are the 3 main roles of the male reproductive system?

Answer 1

1. sperm production
2. hormone synthesis
3. the sexual act

Question 2

What are the parts of the male anatomy?

Answer 2

• urethra (common passage for semen and urine)
• scrotum (temperature regulation)
• testis (es) (spermatogenesis + hormones - testosterone) - outside body for temp regulation
• epididymus (sperm storage - has head, body and tail which feeds into the vas deferens)
• seminal vesicles*
• prostate gland*
• bulbourethral glands*
• vas deferens (transports sperm)
• denotes accessory glands

Question 3

Describe the role of the accessory glands in the composition of the fluid ejaculated

Answer 3

1. seminal vesicles, volume 60% (alkaline), composition = fructose, semenogelin, prostaglandins. For ATP (energy), coagulation (keep sperm together), smooth muscle contraction (along vas deferens)
2. Prostate, volume 25% (acidic), composition = citric acid, prostate specific antigen (PSA). For ATP, and disrupt clot (allow sperm to become free on their own)
3. Bulbourethral gland, volume 5% (alkaline), composition = mucus. For lubrication

Question 4

Describe the testis anatomy + cell types

Answer 4

• located inside the scrotum (external)
• conditions + temp (2 degrees C below normal body temp) v important (for propre cell division and maturation - spermatogenesis)
• testicular temp regulated through the contraction and relaxation of the cremaster muscles to elevate or lower the position of the testes
• epididymis comes into testis -> efferent ductules -> rete testis -> eventually to seminiferous tubule
• 2 main cell types: Sertoli cells (inside), and Leydig cells (outside) - both play a key role in spermatogenesis
• contain blood testes barrier (BTB) - barrier between genetic makeups - seperation between mitotic cells and meoitic cells (mitosis above, meiosis below) - unzips to let cells pass through

Question 5

Describe spermatogenesis

Answer 5

• mitosis gives rise to a pool of genetically identical germ cells called spermatogenia (diploid)
• spermatogenia remain close to basement membrane to maintain a population that the developping spermatocytes are recruited from to undergo meioisis
• mature sperm, known as spermatozoa, are located closest to the lumen, generated only after completing meiosis I and II (haploid) (secondary spermatocytes -> spermatids) - generate genetically distinct cells
• poses potential problem since the immune system is effective at destroying “foreign” or non-self cells, but the presence of tight junctions between sertoli dells forms the blood-testes barrier to maintain an immunologically privileged environment for these cells
• in any given section of the seminiferous tubule, spermatogenesis proceeds in a regular sequence (~1500/sec)
• needs testosterone and time to generate spermatazoa from spermatogenic stem cells ~ 30-40 days
• all starts in puberty and spermatogenesis requires temperatures < 37 degrees C

Question 6

What are the stages of spermatogenesis

Answer 6

1. spermatogenia - undergo mitosis - produce primary spermatocytes
2. primary spermatocytes - undergo meiosis I to generate secondary spermatocyte containing chromosomes with two unique chromatids
3. secondary spermatocytes - complete meiosis II to give rise to spermatids containing single chromatid
4. spermatids - differentiate through process called spermiogenesis to produce spermatozoa with tail and head structures
5. spermatozoa - mature sperm which undergo further alterations to acquire motility and fertilization capacity

Question 7

Describe spermatozoa

Answer 7

• spermatids appear as rounded cells -> through spermiogenesis, the spermatozoa gain an acrosome, flagellum, undergo nuclear condensation and numerous mitochondria organize in the midpiece
• head contains genetic material - has an acrosome (membranous organelle) at its tip and contains a haploid set of chromosome in a compact inactive state
• acrosome contains digestive enzymes including hyaluronidase and acrosin which break down the outer membrane of the ovum called the zona pellucida during fertilization
• mid-piece contains mitochondria and a single centriole, a tail or flagella
• spermiation, shedding residual cytoplasm and then release into the lumen - mature spermatozoa are released from the Sertoli cell into the tubule lumen and travel to the epididymus
• head and tail develop polarity

Question 8

Describe the regulation of spermatogenesis - steroidogenesis

Answer 8

• steroidogenesis provides hormonal control (production of testosterone, etc, from cholesterol)
• Leydig cells play important role through hormone synthesis
• spermatogonia are present at birth but the process of spermatogenesis is initiated at puberty when sufficient levels of testosterone begin to be synthesized
• testosterone is a steroid hormone derived from cholesterol - testosterone one of the most abundant androgens here
• first step of steroidogenesis = conversion of cholesterol to pregnenolone (by action of StAR - transport protein - and cytochrome P450scc - cleavage - rate limiting if not present, etc)
• after pregnenolone is produced in mitochondrial, transported to the endoplasmic reticulum
• precursor to testosterone is androstenedione - converted to testosterone via the action of 17-B-hydroxy-steroid dehydrogenase (rate limiting step)
• testosterone can be converted to DHT (Dihydro-testosterone) by the action of 5a-reductase - DHT is more potent form
• testosterone can also be converted to estradiol via aromatase

Question 9

Describe the gonadotropin regulation for steroidogenesis

Answer 9

• FSH and LH are released (in pulsatile fashion - pulse generator) in response to gonadotropin releasing hormone (GnRH) from the hypothalamus, and regulation of these hormones occur through negative feedback - testosterone acts back on anterior pituitary and hypothalamus
• LH and FSH both have alpha and beta subunits - beta more important for both

Question 10

Describe the pulse mechanism of LH + FSH regulation?

Answer 10

• pulsatile regulation
• the pulse generator of GnRH has different speeds
• fast pulses = higher levels of output of LH, less FSH
• slow pulses = more FSH, less LH

Question 11

Describe the action of LH and FSH

Answer 11

• Leydig cells produce testosterone in response to luteinizing hormone (LH) released from anterior pituitary gland
• LH binds to receptor on Leydig cell and leads to GPCR activation to increases steroidogenesis (cholesterol - testosterone)
• testosterone has 2 fates -> can go into circulation or -> can diffuse across membrane and move into the Sertoli cell
• follicle-stimulating hormone (FSH) also released from anterior pituitary, acts mostly on Sertoli cells
• will activate GPCR, which increases ABP levels (androgen binding protein), and androgen receptor levels
• ABP binds testosterone to hold onto it
• need to maintain high levels of testosterone in Sertoli cells (for spermatogenesis) and ABP is one of the ways to maintain this
• AR increase will also lead to increased transcription, more genes for fluid production, etc

Question 12

What is another method of negative feedback?

Answer 12

• inhibin (peptide hormone) produced by the Sertoli cells inhibits FSH synthesis

Question 13

Describe puberty and the hormonal changes in boys

Answer 13

• testosterone levels have a large wave in younger fetus, then goes low
• another large wave at a couple of months
• then low until testosterone levels increase lots at puberty (switched on by pulse generator)
• growth action increases lots with testosterone

Question 14

Describe the systemic effects of testosterone

Answer 14

• in utero + development
• larynx development (thickening of vocal cords)
• required for muscle and bone growth (growth plate closure generally requires estrogen)
• more red blood cells - helps to produce

Question 15

What are the sites of specific testosterone or DHT action?

Answer 15

1. Testosterone:
   - in-utero: embryonic development
   - post-pubertal secretory activity
   - pubertal growth of larynx and bone
   - anabolic effects on muscle
   - stimulation of spermatogenesis and libido
2. DHT
   - in-utero: embryonic development (prostate) and descent of the testes
   - phallic growth
   - development of pubic hair and underarm hair
   - activity of sebaceous glands

Question 16

What is SHBG?

Answer 16

• carries testosterone in circulation (similar to ABP)
• diffuses into the target cell

Question 17

Describe the use of testosterone in medicine?

Answer 17

• steroids are prescribed to treat hypogonadism, body wasting in patients with AIDs, other diseases that result in loss of lean muscle mass, treating metabolic syndrome, transgender population and aging
• significantly greater gains in body mass and lean body mass
• up-regulation in genes involved in myogenesis and muscle protein synthesis
• testosterone has roles/ actions outside reproduction

Question 18

Where does the production of sex hormones occur in the female reproductive system?

Answer 18

the ovaries
- the two ovaries are located inside the pelvis, suspended on either side of the uterus

Question 19

Describe the female anatomy

Answer 19

• uterus (site of implantation)
• bladder (below uterus - during pregnancy, heavy uterus sits on bladder, have to pee more)
• urethra (tube from bladder)
• fallopian tubes (passage for sperm and oocyte - where sperm and egg meet) - not attached to ovary, but the fimbriae ends are very close by
• ovaries (oogenesis + hormones) - attached to uterus via ligament
• cervix (entrance to uterus)
• vagina (site of sperm deposition, removal of menstrual fluid)

Question 20

Describe oogenesis

Answer 20

• the process required to produce oocytes, the female reproductive cells
• begins with cells known as oogonia - all produced prior to birth (similar to spermatogonia in males) - all mitosis occurs before birth (diff from continuously regenerating pool in males)
• 5-10 million oogonia produced while in utero
• up to 1-2 million oogonia start meiosis I to become primary oocytes around time of birth
• primary oocytes are arrested in prophase I at least until puberty
• by puberty a female will have between 200,000 and 400,000 primary oocytes (others undergo atresia - die)
• at puberty, primary oocytes undergo process of recruitment stimulated by hormonal changes
• small pool of primary oocytes continue to develop (meiosis 2) and eventually give rise to a single secondary oocyte that is ovulated (these cells are still halted at metaphase 2 of meiosis 2 though, awaiting sperm)
• by recruiting only a few primary oocytes each month, females have a supply of reproductive cells that will persist until they are beyond their reproductive years (menopause).

Question 21

What are the stages of oogenesis?

Answer 21

1. oogonia
2. primary oocyte (birth -> puberty)
3. secondary oocyte - requires high LH exposure
4. ovum (only 1)

Question 22

Describe folliculogenesis
what are the major changes between stages of the follicles?

Answer 22

• the follicle is the package for the oocyte
• presence of “supporting cells” that promote the maturation of the oocyte (surround)
• follicular phase = follicle developing before ovulation
  1. primordial -> primary follicle (average 14 days) - 40 -> 100 micrometers
• at early stages of follicles developing, major transition involves granulosa cells changing from flat cells to cuboidal cells
• also begin to have presence of zona pellucida - glycoprotein rich extracellular matrix secreted by oocyte, kind of like the egg shell
• these primary follicles begin to express FSH receptors in granulosa cells but are not really functional (FSH independent before secondary follicle)
  2. secondary follicle - 200 micrometers
• once developed, three major cell types exist: primary oocyte, layers of granulosa cells (rapid mitosis) and theca cells
• theca cells develop from the stroma (outside of granuloma cells) and along with granulosa cells become important for steroidogenesis
• pre-antral follicles (antrum hasn’t developed yet).
• need FSH (and LH) responsiveness to proceed to antral stage
• start to produce estrogen (E2) and AMH which inhibit other hormones
  3. early antral follicle - 400 micrometers
• antrum develops - Antrum = fluid filled space, secreted by granulosa - full of growth factors, steroids, etc.
  4. Graafian follicle
• antrum fullys develops
• considerable size
• ready to ovulate
  5. Dominant graafian follicle - 16-20 mm
• large antrum
• contains 2 types of granulosa cells: corona radiata (directly around oocyte), and cumulus oophorous (anchors granulosa cells)

Question 23

How many gametes are produced from female oogenesis?

Answer 23

• in each monthly cycle, up to 50 primary oocytes begin to mature, but generally only one gives rise to a secondary oocyte (and one polar body) and eventually ovulated for possible fertilization
• should fertilization occur, a second polar body will form after meiosis II is completed
• unlike the male cells, there are not 4 haploid gametes (spermatocyte -> 4 spermatozoa) produced through meiosis 2, but rather one egg (gamete) produced
• not equal distribution of mitochondria/ cytoplasm between the secondary oocyte (gets all) and first polar body (normally will disintegrate)
• in terms of follicles, only one dominant (Graafian) follicle will form, others undergo atresia

Question 24

What are the stages of folliculogenesis?

Answer 24

1. primordial follicle (in utero -> puberty)
2. primary follicle (puberty)
3. secondary follicle
4. Graafian follicle (has antrum present) - at same level as secondary oocyte
   - eventually becomes corpus luteum

Question 25

How long is the total process?

Answer 25

- while the cycle is known to be 28 days, the process really starts much earlier - ~80 days - start with large cohort (50-100) of primary oocytes = pre-antral follicles - many are not able to survive, end up with group of 6-12 secondary oocytes (graafian follicles) that are responsive to FSH - 1 is selected / survives over the rest (rest undergo atresia) - this is the dominant follicle - process starts cycles before the one where the dominant follicle participates

Question 26

What are the hormones involved in follicular development? Feedback?

Answer 26

- GnRH, LH and FSH - primary sex hormone = estrogens, such as estradiol (regulate feedback pathway) - both negative and positive feedback exists with estrogens, depending on the phase of follicular development that is occurring - negative feedback early, positive towards ovulation - inhibin suppresses secretion of LH and FSH - estrogen is dominant in follicular phase - progesterone is also produced during latter part of cycle (dominant in luteal phase)

Question 27

What are the effects of FSH and LH? What cells do they act on?

Answer 27

1. LH acts on Theca interna cells (receptors present) - theca cells perform first part of steroid production (cholesterol to androgens) - via cAMP from LH 2. FSH acts on granulosa cells (receptors present) - androgens travel from theca cells to granulosa cells where the rest of the steroid production takes place (androgens to estrogens) - also via cAMP action from FSH - Androgens, estrogens and progestins also enter the systemic circulation to have a variety of effects on reproductive and peripheral tissues

Question 28

Describe the steroidogenesis in females

Answer 28

- cholesterol starting material - sTAR (steroid acute regulatory protein) - rate limiting enzyme, transports cholesterol into mitochondria - Androstenedione (pre-cursor to testosterone) - androgen - sometimes will have the brief testosterone production before estradiol conversion - generally, 17-B-hydroxy-steroid dehydrogenase (17B-HSD) and aromatase will work together at same time to get direct conversion of androstenedione to estradiol - combined function - estrogen mainly produced early/mid follicular period (pre-ovulation)

Question 29

Describe the hormone fluctuations in female follicular phase

Answer 29

- early on in this phase, thought to be hormone independent - FSH is main driver during follicular phase, higher - FSH responsiveness decides whether the oocytes + follicles are successful -> develop follicles to mature (antral) follicles - LH relatively minor during follicular phase but large increase (wave) right before ovulation (required for meiosis) - positive feedback from estrogen cause the LH surge 12-36 hours before ovulation - estrogen + FSH stimulate granulosa cells to also express LH receptors, required for ovulation to occur - LH receptors facilitate increase in progesterone