Reproductive system Flashcards
What are the 3 main roles of the male reproductive system?
- sperm production
- hormone synthesis
- the sexual act
What are the parts of the male anatomy?
- 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
Describe the role of the accessory glands in the composition of the fluid ejaculated
- seminal vesicles, volume 60% (alkaline), composition = fructose, semenogelin, prostaglandins. For ATP (energy), coagulation (keep sperm together), smooth muscle contraction (along vas deferens)
- Prostate, volume 25% (acidic), composition = citric acid, prostate specific antigen (PSA). For ATP, and disrupt clot (allow sperm to become free on their own)
- Bulbourethral gland, volume 5% (alkaline), composition = mucus. For lubrication
Describe the testis anatomy + cell types
- 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
Describe spermatogenesis
- 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
What are the stages of spermatogenesis
- spermatogenia - undergo mitosis - produce primary spermatocytes
- primary spermatocytes - undergo meiosis I to generate secondary spermatocyte containing chromosomes with two unique chromatids
- secondary spermatocytes - complete meiosis II to give rise to spermatids containing single chromatid
- spermatids - differentiate through process called spermiogenesis to produce spermatozoa with tail and head structures
- spermatozoa - mature sperm which undergo further alterations to acquire motility and fertilization capacity
Describe spermatozoa
- 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
Describe the regulation of spermatogenesis - steroidogenesis
- 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
Describe the gonadotropin regulation for steroidogenesis
- 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
Describe the pulse mechanism of LH + FSH regulation?
- 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
Describe the action of LH and FSH
- 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
What is another method of negative feedback?
- inhibin (peptide hormone) produced by the Sertoli cells inhibits FSH synthesis
Describe puberty and the hormonal changes in boys
- 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
Describe the systemic effects of testosterone
- 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
What are the sites of specific testosterone or DHT action?
- Testosterone:
- in-utero: embryonic development
- post-pubertal secretory activity
- pubertal growth of larynx and bone
- anabolic effects on muscle
- stimulation of spermatogenesis and libido - DHT
- in-utero: embryonic development (prostate) and descent of the testes
- phallic growth
- development of pubic hair and underarm hair
- activity of sebaceous glands
What is SHBG?
- carries testosterone in circulation (similar to ABP)
- diffuses into the target cell
Describe the use of testosterone in medicine?
- 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
Where does the production of sex hormones occur in the female reproductive system?
the ovaries
- the two ovaries are located inside the pelvis, suspended on either side of the uterus
Describe the female anatomy
- 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)
Describe oogenesis
- 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).
What are the stages of oogenesis?
- oogonia
- primary oocyte (birth -> puberty)
- secondary oocyte - requires high LH exposure
- ovum (only 1)
Describe folliculogenesis
what are the major changes between stages of the follicles?
- 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)
How many gametes are produced from female oogenesis?
- 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
What are the stages of folliculogenesis?
- primordial follicle (in utero -> puberty)
- primary follicle (puberty)
- secondary follicle
- Graafian follicle (has antrum present) - at same level as secondary oocyte
- eventually becomes corpus luteum
How long is the total process?
- 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
What are the hormones involved in follicular development? Feedback?
- 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)
What are the effects of FSH and LH? What cells do they act on?
- LH acts on Theca interna cells (receptors present)
- theca cells perform first part of steroid production (cholesterol to androgens) - via cAMP from LH - 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
Describe the steroidogenesis in females
- 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)
Describe the hormone fluctuations in female follicular phase
- 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