Repro Flashcards
(82 cards)
1
Q
difference between sexual determination and differentiation
A
determination - genes (eg. being XX or XY) determined by SRY presence
differentiation - what sex your internal and external genitalia develops as
2
Q
gonadal development
+ the 3 waves of cell invading genital ridge
A
genital ridge –> ovaries / testes depending on presence of SRY gene
- Primordial germ cells –> sperm/ oocytes
- Primitive sex cords –> Sertoli cells (SRY present) / granulosa cells
- Sertoli cells –> AMH release
- Granulosa cells –> required for conversion of androgens to E2 in menstraul cycle - Mesonephric cells –> blood vessels/ leydig (SRY) / theca cells (no SRY)
- Leydig –> testosterone release
- Theca
3
Q
what 2 ducts determine internal genitalia + the hormones that influence its development
A
mullerian ducts - female internal
develops if absence of AMH (sertoli) and Testosterone (leading)
wolffian ducts - male internal
develops due to presence of AMH / Testosterone
4
Q
where is the SRY gene located
A
on the short arm (p)
5
Q
why tissue is the genital ridges derived from
A
somatic mesenchymal tissue
6
Q
what determines external genitalia differentiation
A
presence/absence of DHT
testosterone ——–5a-reductase—–> DHT
males and females both have this enzyme but testosterone only in males
DHT causes differentiation of male external genitalia
- clitorial enlargement
- labia fuses - scrotum
- prostate forms
no DHT = female external differentiation
7
Q
what receptors do DHT bind to
A
testosterone but they are more potent than testosterone
8
Q
what is SRY
A
Sex determining region Y (SRY)
switches on during development
if it does not switch on - ovaries develop
9
Q
what is gonadal dysgenesis
A
incomplete sexual differentiation
10
Q
what is
- androgen insensitivity syndrome
- 5a-reductase deficiency
- turners syndrome
- congenital adrenal hyperplasia
A
all types of gonadal dysgenesis
AIS: testosterone is produced in males but faulty receptors
AMH is still present so wolffish ducts but failure/abnormal external male genitalia
5a-reductase deficiency: no DHT
- normal internal
- faulty external (eg. no descent of testis)
turners: missing/inactivated one X chromosome 45
- ovaries present
- but small/’streaked’ because you need 2 Xs for full ovarian development
CAH: female exposed to high levels of androgens
- no testes as no SRY
- but presence of both mullerian and wolffian ducts
- external genitalia is male-like
11
Q
explain the HPG axis
A
- kisspeptin to hypothalamus (inactive 145aa and cleaved into active forms - there are 4)
- hypothalamus releases GnRH associated peptide (GAP) 56aa which is cleaved by endopeptidases at processing site P to form decapeptide (10aa) = active GnRH
GnRH is released in a pulsatile way to pituitary (otherwise continuous, GPCR will decouple from 2ndary messenger systems)
- fast pulses–> LH from pituitary
slow pulses–> FSH
due to GnRh being released in pulses, so are the gonadotrophins
- gonads produce testosterone/ progesterone/ oestrogen (can also negative feedback to hypothalamus / pituitary)
12
Q
what is the similarity and difference of the 3 gonadatrophins
A
LH/FSH/hCG all have same alpha-subunit (92)
which is released in excess
but have different beta which is limited therefore limits hormone conc
- LH: 121
- FSH: 110
- hCG: 145
also hCG is NOT produced by pituitary
13
Q
2 major endocrine events of puberty
A
- ADRENARCHE
- adrenal maturation (zona reticularis)
- secretion of adrenal androgens (DHEA/DHEAS)
- enter circulation to tissues where it can be converted into testosterone / DHT
first thing as a result of DHEA increase we see =
pubarche also occurs (growth of pubic/axillary hair)
increased sebum production (–> acne)
- GONADARCHE
- reactivation of HPG axis (pulsatile release of GnRH)
- epiphyseal growth- oestrogen (initial low conc: growth / high conc: epiphyseal fusion)
14
Q
2 types of pilosebascous units
A
- Vellus PSU differentiate to either:
- terminal- PSU: facial hair
- APO-PSU: axillary hair - Sebacous
- large sebaceous gland
15
Q
what is puberty
A
non reproductive —> repoductive
+
where secondary sexual characteristics develop (primary = at birth)
16
Q
what is consance
A
smooth ordered progression of change
every child undergoes the same order of changes
but the onset/duration will vary
17
Q
what typically is the first sign of puberty for girls/boys
A
girls: thelarche (breasts enlargement)
boys: testicular volume increasing >4ml
18
Q
when does fertility ‘begin’ for boys/girls
A
girls: 1st year of period
boys: from beginning of puberty (as soon as HPG axis awakens because FSH—> Sertoli cells–> spermatogenesis)
19
Q
2 types of precocious puberty
A
- CENTRAL
- gonadotrophin dependent
- consance is maintained
- excess GnRH/gonadotrophin secretion
- high FSH/LH/E2/Testosterone - PERIPHERAL
- gonadotrophin independent
- consance is not maintained
- low FSH/LH but high E2/testosterone
20
Q
when is it considered delayed puberty
A
girls: >13yrs / >18yrs for menarche
boys: >14yrs
21
Q
explain process of primordial germ cells in development of a foetus and the form they arrest in for girls until puberty
A
- if genital ridge–> ovaries
- PGC will enter become oogonia and differentiated into egg/oocytes
- mitosis (increase in number - but still diploid)
- meiosis begins
- BUT arrest in meiosis anaphase I = primary oocytes
22
Q
folliculogensis
A
PRE-ANTRAL PHASE(gonadotrophin independent)
once puberty starts a few follicles will start growing
- multiplication of granulosa cells
- oocyte grows by synthesising protein
- thick protective layer = zona pellucida
2nd layer of basal lamina differentiates into theca cells
so layer around oocyte:
zona pellucida, granulosa cell, basal lamina (secreted by granulosa), theca cells
ANTRAL PHASE (gonadotrophin dependent)
- follicle grows
- fluid enters via gaps of granulosa = antrum
- antrum pushes oocyte to the side
- granulosa cell surrounding oocyte = specialised = cumulous cells
FOLLICLE RECRUITMENT
- only follicles grown to right side will respond to FSH = recruited
- continue growth
- only one will be selected for ovulation –> grow massively (Graafian follicle)
23
Q
what is the 2-cell 2-gonadtrophin theory
A
theca cells have LH receptors + are highly vascularised (blood supplies LH)
stimulates synthesis of cholesterol—-> androstenedione(androgens)
released around body
some to granulosa cells: androstenedione—-aromatase—> E2 (this process is driven by FSH)
oestrogen drives granulosa cells (positive) as well as negative feedback to HPG
24
Q
aims of menstraul cycle
A
- select single oocyte to be fertilised
- regular spontaneous ovulation to maintain fertility
- ensure correct no. of chromosomes in eggs
- cyclical changes in vagina/cervix/utereus
- preparation of uterus to receive a potential embryo + support it
25
2 phases of menstraul cycle
starts from first day of bleeding
1. follicular phase
2. luteal phase
luteal phase ALWAYS lasts only 14days
follicular phase can vary per woman
a regular period = within 4 days difference from last period
26
describe whole menstraul cycle
1. CL dies
2. progesterone falls = HPG axis inhibition is stopped
3. rise in FSH
4. recruitment of antral follicles that are of the right size/respond
5. they produce a lot of oestrogen
6. negative feedback
7. decrease in FSH
8. (window of opportunity) only the dominant follicle is able to survive the low FSH levels
- more FSH receptors
- LH receptors on granulosa cells
- more granulosa cells - more E2 production - more negative feedback to decrease FSH for the others
9. dominant follicle produces E2
10. sustained levels of E2 for 2 days (>300) causes HPG to switch back on
11. LH surge:
- oocyte released
- empty follicle --> CL
- lutenisation of granulosa/theca
the oocyte will have undergone meiosis I in dominant follicle becoming a secondary oocyte (forming a 1st polar body with the other half of the chromosomes)
secondary oocyte will being meiosis II but will arrest again and only complete when fertilised (+create a secondary polar body containing identical sister chromatids)
12. high progesterone from CL
13. decrease in FSH/LH
(we expect the oocyte to have ovulated + fertilised and so prevent other follicles growing)
14. after 14 days, if no pregnancy, CL dies
15. decrease in progesterone so cycle begins again
27
what receptors are on the corpus luteum (and therefore maintains it)
LH
hCG (if pregnant - trophoblast of embryo/blastocyte will produce)
the hCG has similar structure to LH so it binds to LH receptors
28
what are the 3 layers of uterus
perimetrium
myometrium --> circular/ figure of 8 spiral/ longitudinal
endometrium
29
what hormone determines the size of uterus
oestrogen
high oestrogen---> high proliferation /cell division --> expand
30
how does the follicular and luteal phase affect the endometrium
follicular (high oestrogen)
- proliferation
- cell division
- glands expand
- high vascularity
luteal (high progesterone)
- differentiation / mature
- cell division decreases
- glands secrete glycoproteins/lipids
- high vascularity --> oedema
at the end of luteal (decrease in progesterone) = menstruation
1. endometrium releases prostaglandins
2. constriction of vessels
3. necrosis/hypoxia + proteolytic enzymes from necrotic tissue
4. vessels dilate --> bleeding
31
name the parts of the uterine tube
fimbriae--> infundibulum --> ampulla --> isthmus
32
name the parts of the uterine walls
```
outer= serosa
smooth longitudinal
circular muscle fibres
mucosa with 2 main cell types
- secretory: nutrients for early embryo
- columnar ciliated epithelium: to waft oocyte along down tube
```
33
how are uterine tubes affected by follicular/ luteal phase
follicular phase (high oestrogen)
- differentiation
- high secretions
- ciliary cells waft
- mucosa increases in height
luteal (high progesterone)
- undifferentiation
- stop cilia/secretion
- decrease in height of mucosa
34
2 ways of testing for blocked tubes
1. laproscopy and dye
(insert dye via cervix and insert laprocscope via abdomen to see if dye appears in pelvic cavity)
2. hystero salpingo-contrast sonography
(uterus with dye via vagina and use ultrasound to see if it makes its way to tubes)
35
how does the follicular/luteal phase affect the cervix
mucosa:
FOLLICULAR (oestrogen)
- less viscous mucosa
- contains glycoproteins = aligned = microscopic channels = sperm can swim up the channels
LUTEAL (progesterone)
- more viscous due to less secretions
- mesh like glycoproteins to stop sperm
36
describe spermatogenesis
1. mitosis of spermatogonia to increase number
2. there are 2 types:
- A: that stay as sperm that will keep dividing via mitosis/ become B
- B: commit to meiosis
3. meiosis --> spermatocytes
4. spermiogenesis (losing cytoplasm/elongation/movement of cellular components) --> spermatids
37
where are leydig and Sertoli cells located within the testes
Sertoli cells = within seminiferous tubules
| leydig = outside of seminiferous tubules (between them)
38
where/what does seminal fluid receive secretions from
1. bulbs-urethral gland
- lubricates inside of urethra
- neutralises acidic urine and friction
- clear viscous, high in salt
2. seminal vesicles - fructose energy
- PG
- vit C
- enzymes
- FRUCTOSE for energy
3. Prostate - liquefaction later
- milky white component
- proteolytic enzymes
- prostate specific antigen
39
if semen does not liquefy later, what is the problem
prostate not producing the proteolytic enzymes
40
what is a spermatozoon and describe 2 adaptations to help with its function
a mature sperm
mitochondria produces ATP --> axoneme fibres to slide against each other--> power to pull flagella --> propel sperm forward
acrosome at front of head
4-18hrs--> capacitation--> explodes and releases enzymes to help cut through outer layer of egg
41
why can high oestrogen lead to DVT
oestrogen in the liver stimulates clotting factors
42
why is the seminal fluid removed before undergoing capacitation
seminal fluid consists of inhibiting factors
43
what occurs during capacitation
sperm gets closer to egg = alkaline environment
CatSper channels open (voltage gated cation channels set by pH)
ca influx
sperm gets hyperactivated
tail beats more forcefully (higher amplitude and frequency)
44
what occurs during acrosome reaction
capacitation must occur before
- when sperm is right next to the egg
- acrosome will burst release hyalurondiase
- this will digest the cumulus cells and corona radiata (digests hyaluronic acid)
- sperm reaches zona pellucida
- binds to ZP3 (human specific) triggering TRUE acrosome reaction
- enzyme across digests zona pellucida and sperm enters oocyte
45
what happens when sperm and oocyte fuse (syngamy)
1. sperm nuclei falls into egg (tail is lost)
2. sperm has special PLC-zeta (PLC--> PIP2--> IP3+DAG--> increase in Ca)
3. triggers cortisol reaction --> releases enzymes to cleave adhesions molecules from sperm to stop polyspermy
also triggers oocyte to complete meiosis II
4. there are 2 pronuclei (maternal and paternal nucleus have own distinct membranes around nuclei) that will undergo DNA replication
5. they will fuse
6. mitosis so that each daughter cell has 46 chromosomes
46
give the expected timeline for cell division after the 2 pronuclei fuse in the egg
after 3/4 days --> 6-8 cells = morula
after about 5 days --> 100 cells = blastocyst
blastocyst has a blastocele fluid cavity with a trophoblast surrounding it (this will become placenta)
47
where is androgens (testosterone) produced
mainly testes
```
adrenal cortex (glomerulus reticularis)
adipose tissue
```
48
what gonadotrophin controls leydig and Sertoli cells
LH - leydig
FSH - sertoli
Leydig cells will produce testosterone which will act on Sertoli cells for spermatogenesis to occur + AMH release
49
mechanism of testosterone once entered in a cell
either:
bind to its nuclear receptor in the cytosol then
-growth of wolffian ducts ---> internal male genitalia
-initiate spermatogenesis / maintain in adults
or
be converted to DHT (via 5a-reductase)
-binds to same testosterone receptor (but more potent)
-therefore amplification of testosterone action
-external genitalia differentiation
-sexual maturation
-puberty
50
what are 5a-reductase inhibitors used to treat
- prostate cancer
| - balding
51
2 types of 5a reductases
type I - scalp/skin
type II - genital skin/prostate
52
what is danazol and cyproterone acetate and what are they used to treat
(uses of androgens/anti-androgens)
danazol = androgen derivative
- feedback to decrease LH/FSH
- but not converted into oestrogen
- to decrease ovulation/breast tenderness(mastalgia) /menorrhagia (heavy periods)
- endometriosis
cyproterone acetate = inhibits peripheral androgen receptors
- precocious puberty
- supress initial surge effects of goserelin and buserelin
- acne
- hiturism
- virilisation in women
53
what effects would you see if you gave GnRH agonists vs. GnRH antagonist analogues
agonists
- initial LH/FSH increase
- but will stay bound to GnRH receptor --> desensitise (needs to be pulsatile)
- long term will decrease gonadotrophin
- used to treat prostate cancer/endometriosis
antagonists
- no initial LH/FSH increase
- they just block the receptors
54
primary and secondary hypogonadal syndrome
primary = HYPERgonadotrophic hypogonadal
- testes failing to respond to LH
- chromosomal abnormality: kinefelter syndrome (47XXY)
- LH/FSH is high due to neg feedback from low/no testosterone
- could give testosterone but risk of early epiphyseal closure (faltered growth)
secondary = HYPOgonadotrophic
- pituitary failing to produce gondatrophin LH/FSH
- kalmann's syndrome (loss of smell = distinctive feature)
- giving synthetic GnRH will take time until change is seen
55
around how many days after ovulation does blastocyst enter the uterus
5/6
if too early --> no implantation
too late --> ectopic
56
what happens after blastocyst reaches epithelium cells of endometrium
enzymes on endometrium help dissolve zona pelucida
trophoblasts invade ---> synctiotrophoblast and cytotrophoblast
as synctiotrophoblast continue to invade there are 2 cell divisions occurring:
- cytotrophoblast --> placenta
- inner cell mass --> epiblasts and hypoblast --> 3 germ layer( ecto, endo and meso)
trophoblasts that down differentiate --> chorion and extra embryonic mesoderm
fluid filled sac--> yolk (circulation for first few days) + amnion (which later covers foetus --> amniotic fluid)
chronic villi form from embryonic mesoderm
endometrium has spaces = lacuna which will fill with maternal blood
57
why do we use B-hCG to detect pregnancy
secreted by synctiotrophoblast to maintain CL during pregnancy (cl produces steroids oestrogen/progesterone maintaining the endometrium)
alpha-subunit is same as LH/FSH
but beta is different
58
what hormonal changes are there with pregnancy
placenta
- takes over steroid production from CL (progesterone/E2/E3)
- peptides: hCG/hPL/GH
hPL --> insulin resistance
placenta also produces its own
-cortisol: foetal lung maturity/ mineralocorticoid action / insulin resistance
-CRH leading to increase of ACTH--> inc. DHEA--> inc. prostaglandins in uteroplacental tissues--> inc. BF + cervical contractions
(labour initiation)
pituitary
- GH
- thyroid
- prolactin (suckling increases it; progesterone inhibits it)
- corticotrophin releasing hormone
59
what contributes to weight gain with pregnancy
- foetus and placenta
- fat + protein
- breasts
- uterus
water gain
- placenta renin --> increases RAAS
E2 --> unregulated angiotensin synthesis in liver
however preg. women are resistant to AT2 receptor so decrease in vasoconstriction
(RAAS- constriction)
- E2/Prog act as mineralocorticoid--> increase sodium retention -->increase Blood volume
- connective tissue/ligaments take on water and become softer
- resetting osmostat - lower threshold --> drink more
60
why is there an increase in o2 consumption with pregnancy
CO2 sensitivity increases + anatomy change of ribcage more out--> breathing more/deeply--> minute volume increases--> high arterial O2 and lower pCO2 ----> steeper gradient for gas exchange
61
how is CVS affected with pregnancy
- expanding uterus pushes on heart --> change in sounds and ECG
- E2--> NO--> peripheral vasodilation --> dec. TPR---> increase in perfusion of uterus/placenta/kidney/skin etc
- neoangiogenesis and increase in skin capillaries(spider naevi) to increase heat loss
pregnancy = LOW pressure, HIGH volume
62
GI changes with pregnancy
- increases in appetite/thirst
- dec. GI motility --> constipation
- reduced LOS --> acid reflux
best to eat small frequent
folic acid supplements (400ug/day until week 12) --> DNA production/growth/blood cells for uterus/placenta/fetus
63
urinary system changes with pregnancy
- pee more as baby pushes on bladder
- CL/placenta release relaxin ---> formation of endothelin--> dilation of renal arteries via NO--> UTI risk
- progesterone/VEGF--> inc. resistance to Ang II--> dec. vasoconstriction --> inc. BF to kidney --> inc. in GFR
64
what do you see when "returning to normal" after a pregnancy
Dramatic and rapid fall in steroids on delivery of the placenta.
Most endocrine-driven changes return to normal rapidly.
Uterine muscle rapidly looses oedema but contracts slowly: never returns to pre-pregnancy size.
Removal of steroids permits action of raised prolactin on breast.
65
why does menopause occur?
reduced follicle count
-also normally granulosa cells secrete small amount of AMH which inhibits FSH therefore decreasing recruitment of follicles but as you age less granulosa cells=less inhibition = more follicles lost via recruitment
reduced granulosa cells/function
- as you age they become less effective at producing oestrogen
- less inhibin A and B to suppress FSH
increased chromosomal abnormality of oocyte
- so decreased ability to repair DNA
- increase aneuploidy risk
66
what is clomiphene
drug used to help follicle recruitment (release)
67
what causes shortened cycle(initial) and delayed ovulation/absence in menopause
shortened cycles
- decrease in inhibin B which normally prevents follicular phase
- so you get high oestrogen and LH surges earlier
delayed/absence
- despite high FSH
- faulty granulosa cells
- oestrogen rise is not high enough to induce LH surge
- no ovulation
68
why might you get constant heavy bleeding with menopause
- despite high FSH
- faulty granulosa cells
- oestrogen rise is not high enough to induce LH surge
- no ovulation
- so dominant follicle not recruited/released
- no progesterone produced - constant bleeding?
69
why are UTIs common for pregnant women
- in hospital more = higher diagnosis rate
- high progesterone --> SM relaxation --> urinary stasis --> more likely to be infected
- pregnant women have lower immune system (to prevent attacking foetus)
70
problems that can arise if mother is hyperglycaemic for foetus
- sacral agenesis (sacrum doesn't form) risk
- Congenital heart disease risk
- skeletal malformation risk
- inhibits surfactant production --> resp distress on delivery risk
- neonatal HYPOglycaemia (foetus will produce high insulin but after birth the insulin is too high for glucose in its own blood)
- glycosuria as high glucose--> increases water out of intestitium--> peeing alot--> increase amniotic fluid (polyhydramnios--> uncomfortable for mum
- hypoxic--> jaundice
71
4 high BP pathology classifications
<20weeks
- pre-existing HT (no proteinuria)
- pre-existing HT due to RENAL disease (proteinuria)
>20weeks
- pregnancy induced HT (no proteinuria)
- Pre-clampsia (PET) (proteinuria)
72
why do you get PET
peripheral vasodilation fails so high TPR due to vasoconstriction/vasospasm
most likely due to failure of 2nd wave of trophoblastic invasion at 15/16weeks so normal dilation of vessels do not occur/develop
73
stages of labour
1. contractions---> dilation 10cm
- latent phase: up to 3cm + PGs to inc. permeability in cervix for collagen breakdown/soft
- active phase: up to 10cm (1cm/hr)
2. dilation--> delivery of foetus
- rotation of baby head past pelvic inlet
- delivered with facing mothers back
- rotation for shoulders to come out
3. removal of placenta
- in thigh SYNTOMETRINE (artificial oxytocin and ergometrin)
- umbilical cord is clamped to prevent getting into baby
- placenta dettaches
- check by feeling pubic symphsis
labour complete after placenta has been delivered
74
what is dystocia
despite uterus contracting normally
| the baby does not exit due to physical block
75
which hormone increases contraction and which decreases
oestrogen - increases
progesterone - decreases
76
stimulation of which ANS receptors increases/decreases contraction of myometrium (uterus)
a1 - increases contraction
b2 - decreases contraction (relaxes)
77
describe the myogenic contraction mechanism of uterus
1. interstitial cells of canal initiate slow wave activity
2. depolarisations of these causes AP
3. AP runs down from ICC to SM cells via gap junctions
oestrogen increases the gap junctions--> easier coordination/contractiosn
4. SM contraction via PLC/inc. Ca/MLCK pathway
78
why might hypertonus occur (uterus)
too much contraction over relaxation
high conc of ca in cell than it is being extruded out
therefore incomplete relaxation
79
why does increasing contraction of uterus treat haemorrhage
contracting uterus/ligature decreases bleeding
eg. oxytocin
80
increase in oestrogen increases the synthesis of which 2 types of prostaglandins
PGE2 = vasodilator
PGF2a = vasoconstrictor
but both have an effect to increase myometrium contraction
81
why might it be better to use prostaglandins vs. oxytocin to increase contractions of uterus
oxytocin is dependent on oestrogen
low oestrogen = low oxytocin + low oxytocin receptors
however, there are always many prostaglandin receptors
82
myometrium relaxants for premature birth
- B2 adrenoceptor agonists (salbutamol) they increase PKA
- ca2+ channel antagonists (nifedipine/mg sulfate)
- oxytocin receptor antagonists (retosiban)
- COX inhibitors (NSAIDs)
