Reproductive system Flashcards

1
Q

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

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

What are the parts of the male anatomy?

A
  • 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
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3
Q

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

A
  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
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4
Q

Describe the testis anatomy + cell types

A
  • 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
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5
Q

Describe spermatogenesis

A
  • 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
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6
Q

What are the stages of spermatogenesis

A
  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
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7
Q

Describe spermatozoa

A
  • 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
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8
Q

Describe the regulation of spermatogenesis - steroidogenesis

A
  • 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
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9
Q

Describe the gonadotropin regulation for steroidogenesis

A
  • 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
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10
Q

Describe the pulse mechanism of LH + FSH regulation?

A
  • 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
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11
Q

Describe the action of LH and FSH

A
  • 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
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12
Q

What is another method of negative feedback?

A
  • inhibin (peptide hormone) produced by the Sertoli cells inhibits FSH synthesis
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13
Q

Describe puberty and the hormonal changes in boys

A
  • 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
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14
Q

Describe the systemic effects of testosterone

A
  • 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
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15
Q

What are the sites of specific testosterone or DHT action?

A
  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
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16
Q

What is SHBG?

A
  • carries testosterone in circulation (similar to ABP)
  • diffuses into the target cell
17
Q

Describe the use of testosterone in medicine?

A
  • 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
18
Q

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

A

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

19
Q

Describe the female anatomy

A
  • 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)
20
Q

Describe oogenesis

A
  • 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).
21
Q

What are the stages of oogenesis?

A
  1. oogonia
  2. primary oocyte (birth -> puberty)
  3. secondary oocyte - requires high LH exposure
  4. ovum (only 1)
22
Q

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

A
  • 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)
23
Q

How many gametes are produced from female oogenesis?

A
  • 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
24
Q

What are the stages of folliculogenesis?

A
  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
25
Q

How long is the total process?

A
  • 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
26
Q

What are the hormones involved in follicular development? Feedback?

A
  • 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)
27
Q

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

A
  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
28
Q

Describe the steroidogenesis in females

A
  • 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)
29
Q

Describe the hormone fluctuations in female follicular phase

A
  • 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