Week 8 Flashcards
What are the reproductive systems?
- gonads
- external and internal genitalia/ reproductive tracts
- accessory sex glands
What are external/ internal genitalia?
ducts that transport and or house gametes
What is the female reproductive tract?
mullein duct
What is the male reproductive tract?
wollfian duct
What are accessory reproductive organs?
- transport gamete
- glands: secrete fluids into reproductive tract
What are primary reproductive organs?
gonads
- pared in humans
- testes and ovaries
What are the two major functions of the gonads?
- produce haploid gametes (germ cells)
- produce/ secrete gonadal hormones, either peptide or steroid hormones
What is the production of germ cells called?
gamatogenesis
(spermatogenesis, oogenesis)
What is the production of gonadal hormones called?
steroidogenesis
Name some androgens
- masculinising male sex hormone
- testosterone from testes
- dehydroepiandosterone from adrenal cortex - metabolic intermediate in biosynthesis of androgen and oestrogen sex steroids
What hormones are involved?
steroid hormones (testosterone, progesterone, oestrogens)
From what are steroid hormones produced and where?
cholesterol
in ovaries, testes, adrenal cortex
Can each steroidogenic organ produce all steroids?
No, only those for which it has a complete set of enzymes that modify cholesterol appropriately after firstly converting it to progenolone
- testis - testosterone (androgen)
- ovary - estradiol (estrogen) and porgesterone (progestogen)
Cholesterol (C27) becomes … when activated
Progestogen (C21)
Progesterone (C21) becomes … when activated
Estrogen (C18)
By which are the active steroids produced?
- sequential enzymatic reactions of CYP and HSD enzymes
How do gonads differentiate into testis?
- ovum with C sex chr. fertilised by sperm with Y
- embryo with XY -> male
- sex determining region of Y chr (SRY) codes for production f testis determining factor (TDF)
- TDF directs differentiation into testis
How doe the testis create the rest of the reproductive system male repro tract and external genitalia (phenotype)?
- testis secrete testosterone and Mullein-inhibiting factor
- testosterone converted to dihydrotestosterone
-> promotes development of undifferentiated external genitalia along male lines (penis, scrotum)
-> transforms Wolffian ducts into male repro tract (epididymis, ducts deferent, ejaculatory duct, seminal vesicles) - Mullein-inhibiting factor
-> degeneration of Mullein ducts
How do gonads differentiate into ovaries?
- ovum with X sex chr. fertilised by sperm with X
- Embryo with XX -> female
- no Y chr. no SRY and no TDF
- with no TDF, undifferentiated gonads develop into ovaries
- undifferentiated gonads develop into ovaries
How do the ovaries create the rest of the female repro system - female repro tract and external genitalia (phenotype)?
- no testosterone or Mullerian inhibiting factor
1. absence of mullein inhibiting factor
-> development of Mulllerian ducts into female repro tract (oviducts, uterus)
2. absence of testosterone
-> degeneration of Wolffian ducts
-> development of undifferentiated external genitalia along female lines (eg. clitoris, labia)
What are the functions of testosterone?
- reproductive and non-reproductive actions
eg. secondary sex characteristics, growth/ maturation of genitalia, spermatogenesis, libido at puberty, protein anabolic effect, bone growth at puberty (anabolic effect), - may induce aggressive behaviour
- causes voice to deepen bc vocal folds thicken
- male pattern of hair growth
- controls gonadotropin hormone secretion
How are testosterone effects mediated?
via androgen receptor
0 in target tissue, testosterone converted to estradiol
- ligand for estrogen receptors in testes, prostate, bone, brain
- affects spermatogenesis, bone homeostasis and epiphyseal fusion
What are the functions of progesterone and estradiol in females?
- except both reproductive and non reproductive actions
- 2ndary sex characteristics
- growth and maturation of repro tract
- menstrual cycle
- oogenesis
- parturition
- increase adipogenesis
- increase bone mineral density
What three processes take place in the ovary
- folliculogenesis (production of ovulatory follicle)
- oogenesis (production fo haploid oocyte)
- gonadal hormone synthesis
Name the steps In folliculogeneis
primordial -> primary -> secondary -> pre-astral -> astral -> ovulatory/ Graafian follicle
What two structures perform gonadal hormone synthesis?
- follicle (androstenedione and estradiol)
- corpus lutem (progesterone and estradiol)
How is estrogen secreted?
- follicles contain one ovum, develop in ovary
- primoral oocyte, oocyte and granulosa cells
- granulosa cells: target cells of estrogen and FSH: secrete inhibit - provides -ve feedback to FSH secretion
- transport nutrients to oocytes through gap junctions
- secrete estrogens
What is the function of estrogen?
- similar to testosterone in males
- ova maturation and release (ovulation)
- development of female sex characteristics
- transport of sperm within the female
- breast development in anticipation of lactation
What is the function of progesterone?
- prepares suitable environment to nourish developing embryo/ foetus
- breasts ability to produce milk (lobuloalverolar tissue)
Overview the menstrual and ovarian cycles
menstrual cycle:
menstrual phase day 1-5
proliferative phase days 5-14
Ovulation = day 14
secretory phase day 15-28
ovarian cycle
follicular phase - maturing follicles (till ovulation)
luteal phase - presence of corpus luteum (CL)
Explain how menstruation works
- triggered by decrease of estrogen and progesterone
- hormones decrease when corpus luteum degenerates
- LH surge due to high level of estrogen produced by mature follicle
-> triggers ovulation - LH influences empty follicle to convert into corpus luteum
-> porduces progesterone and estrogen during last phase of cycle (luteal phase)
Where does oogenesis and estrogen secretion take place ?
Within ovarian follicle within first half of reproductive cycle (follicular face)
What happens if the ovulated oocyte Is fertilised?
CL prepares uterus - implantation
What happens if the oocyte is not fertilised?
CL degenerates (luteolysis) > no hormonal support for uterine lining
endometrium disintegrates > menstruation
Where are LH and FSH secreted from?
Anterior pituitary gland
Where is estradiol secreted from?
follicle and CL
Where is progesterone secreted from?
CL only
Where are the testis located?
scrotum
- cool temp imp for spermatogenesis
- several degrees lower than normal BT
What are the testis comprised of?
seminiferous tubules
- site of spermatogenesis
What cell type is found within the seminiferous tubules?
Sertoli cells (within)
Leydig cells (between)
What is the function of Sertoli cells?
- epithelial cells within seminiferous tubules
- support spermatogenesis - protect, support
- secrete inhibin (inhibits FSH, completes -ve feedback loop)
What is the function of Leydig cells?
- interstitial cells
- synthesise/ secrete testosterone (stimulated by LH, -ve feedback)
Hypothalamo-pituitary-testicular axis
hypothalamus -> GnRh -> anterior pituitary -> FSH and LH into testis -> testosterone
1. dihydrotestosterone -> secondary sex organs
2. -ve feedback for hypothalamus or anterior pituitary
Kiss peptin signalling
- Kiss1 neurons in arcuate nucleus of hypothalamus
- Kisspeptin from neurons in ARC stimulate hypothalamus - peptide neurotransmitters
- Kiss1 neurons have receptors for androgens, oestrogen and progesterone
- testosterone indirectly inhibits GnRH secreting neurons by blocking kiss 1 neurons excitatory action on GnRH- secreting neurons (no receptors for androgens)
-> indirect action of testosterone on GnRH secretion through Kiss1 receptors
For what is kisspeptin signalling important?
regulation of GnRH and thus FSH, LH and sex hormone output
What does FSH do in relation to spermatogenesis?
remodels spermatids into highly specialised motile spermatozoa
What hormones stimulate spermatogenesis?
testosterone and FSH
What stimulates testosterone?
LH
How do testosterone and FSH stimulate spermatogenesis?
testosteorne
- stimulates mitotic and meiotic divisions of undifferentiated diploid germ cells
- from spermatogonia into undifferentiated haploid spermatids
FSH
- simulates remodelling of haploid spermatids
- highly specialised motile spermatozoa through spermatogenesis via Sertoli cells
What king of signalling is used by testosterone?
paracrine
- local chem messenger whose effect is exerted only on neighbouring cells in immediate vicinity of its site of secretion
Is the testosterone concentration in testes higher than in the blood?
yes, much secreted locally by leydig cells, retained in intratubular fluid complexed with androgen-binding protein secreted by Sertoli cells
- high to sustain sperm production
What are 2 examples of gonadotropins
FSH and LH
Describe the steps of spermatogenesis in testes
- spermatogonium -> spermatogonia by mitosis
- chromosomes replicate (2 primary spermatocytes w 2n)
- meiosis I (2 2ndary spermatocytes w 2n)
- meiosis II (4 spermatids 1n)
- differentiation (spermatozoa 1n)
- from BM to lumen
- following mitosis, 1 spermatogonium stays to maintain germ cell line
- spermiogenesis
Describe the stops of sperm maturation (spermiogenesis)
- spermatozoa released into lumen of seminiferous tubules (immotile, 20 days)
- move to epididymis by peristaltic contractions and flow lumens fluid (acquire motility)
How long does spermatogenesis last?
64 days
Describe the role of endocrine control of sperm production
- complete spermatogenesis and spermiogenesis dependent on FSH + testosterone
- FSH more important in early stages of meiosis via Sertoli cells
- androgens more important latter+ spermiogenesis
Epididymis
- sperm complete spermiogenesis in caput epididymis
- stored in cuada epididymis prior to ejaculation
- epidermal secretions (eg. glycerylphosphorylcholine and inositol) fuel spermatozoa
Accessory sexual organs/ glands
seminal vesicles
- fructose (anaerobic fructolysis)
prostate gland
- citrate (anticoagulant - chelates Ca2+)
- acid phosphatase (cleaves choline form glycerylphosphorylcholine)
- thrombin (coagulant - promotes lysis of fibrinogen and formation of fibrin)
What are the adaptations in female physiology in pregnancy?
- increased blood flow (30%) - heart enlarges
- increased respiration (20%)
- nutrient diversion
- increased hepatic and renal function
- hypercalcaemia (fatal skeleton)/ osteomalacia and/or osteoporosis
What is the placenta?
- develops after embryo implantation (transient)
- endocrine organ of pregnancy
- maternal and fatal tissue
What is the function of the placenta?
- exchange (maternal and foetal blood)
- secretes hormones
1. human chorionic gonadotropin (hCG)
2. estrogens (estrange, estradiol, estriol)
3. progesterone
What are the placental hormones?
- hCG
- estrogen
- progesterone
- human chorionic somatomammotropin
- relaxin
- placental PTHRP
What is the function of the hCG hormone?
- maintains CL of pregnancy
- stimulates testosterone synthesis in developing testes of XY embryos
What is the function of the estrogen hormone?
- stimulates endometrial growth
- stimulates proliferation of mammary tissue (preparation for lactation)
What is the function of progesterone?
- promotes formation fo cervical mucus plug -> contamination
- suppresses uterine contractions
- stimulates differentiation of lobularveolar systems of mammary glands (for lactation)
- prevents subsequent follicle development and ovulation (-ve feedback on Lh and Feh, suppresses ovulatory LH surge)
- also secreted by CL during first trimester
What is the function of human chorionic somatomammotropin?
- similar to growth hormone and prolactin (lactation)
- reduces maternal use of glucose and promotes breakdown of stored fat > high availability of glucose and FAs for foetus
What is the function of relaxin ?
- softens cervix pre parturition - for cervical dilation at parturition
- loosens CT breaks pelvic bones - in prep for parturition
- also secreted by CL
What is the function of placental PTHRP?
- increases maternal calcium for calcifying fatal bones
- related to parathyroid
What is the corpus luteum?
ovarian structure that develops form ruptured follicle following ovulation (release of ovum from mature ovarian follicle)
What are the hormonal changes during the first trimester of pregnancy?
- placenta secretes hCG -> activates LH chronic gonadotropin receptors in CL -> stimulates progesterone and estradiol synthesis/secretion
What are the hormonal changes during the second and third trimester of pregnancy?
- placenta secretes progesterone and estradiol
- produces estriol form fetal adrenal androgen substrate
What surpasses lactation?
estrogen and progesterone at high levels
What simulates lactation?
prolactin and oxytocin
What is the trigger of imitation of parturition?
- unknown, 4 theories
1. high levels of estrogen - up regulate connexins - gap junctions
- up regulate myometrial receptors for oxytocin
- stimulate local prostaglandin synthesis
2. occytoxin - myometrial responsiveness exceeds critical threshold
- increases Ca2+ - activates MLCK (myosin light chain kinase which trigger contractions)
3. CRH (corticotropin-releasing hormone from placenta) - increase estrogen synthesis form metal adrenal androgens
- increases cortisol (increased local prostaglandin synthesis and lung maturation)
4. inflammation - increased number factor K-B unregulated inflammatory cytokines and increases local prostaglandin synthesis - softens cervix
How can bacterial infections and allergic reactions induce premature labour?
by activating NF-kB
Describe the feedback loop for parturition
- +ve feedback spiral (furgusson reflex)
- more uterine contractions -> pushes foetus against cervix -> neuroendocrine reflex -> more oxytocin secretion -> more prostaglandin production and +ve feedback back to more uterine contractions
-> progressive increase in force
what are the three stages of labor?
- cervix dilation
- birth of baby
- delivering of placenta - afterbirth
How do oestrogen influence parturition?
first spike:
- increase responsiveness to OT
- promotes synthesis of connections within uterine smooth-muscle cells
- inserted into myometrial plasma membranes to form gap junctions
-> smooth muscle contractions
second spike:
- oestrogen’s increase concentration of myometrial receptors for OT
- fetal pressure stimulates receptors in cervix - neural signal to spinal cord -> hypothalamus -> triggers OT release form PP
how does lactation work?
- estorgen and progesterone inhibit lactation
- levels fall during labor
- prolactin stimulates milk synthesis
- oxytocin stimulates smooth muscle of breast in same way it stimulates smooth muscle in myometrium
- more milk ejected, more suckle, afferent arc -> brain stimulated more oxytocin secretion -> milk production
Sex hormone anomalies XO
turner syndrome, female, no SRY, no TDF, 0.04%, infertile
Sex hormone anomalies XXX
female, fertile 0.1%
Sex hormone anomalies XXY
klinefelter syndrome, male, smaller testicles, infertile, 0.1%
Sex hormone anomalies XYY
Jacobs syndrome, male, 2 copies of SRY, super male, less fertile, 0.1%
How does the pill work?
- contains progesterone
- high levels will keep u in the secretory phase
- circle doesn’t start again
meiosis in oocyte
- pre puberty, all oocytes arrested in prophase 1, once a month one cell moves to metaphase 2, decade long arrest greatly increases risk of aneuploidy in human oocytes, miscarriage, trisomy 21
function of Oxytocin
- muscle contraction
- pregnancy and labour contractions of uterus
lactation contraction of myoepithelial cells to release milk
sec intercourse - neruomediator
- recognition
- trust
- romantic attachment
- parent-infant bondin
- addiction, depression
