Repro Flashcards
difference between sexual determination and differentiation
determination - genes (eg. being XX or XY) determined by SRY presence
differentiation - what sex your internal and external genitalia develops as
gonadal development
+ the 3 waves of cell invading genital ridge
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
what 2 ducts determine internal genitalia + the hormones that influence its development
mullerian ducts - female internal
develops if absence of AMH (sertoli) and Testosterone (leading)
wolffian ducts - male internal
develops due to presence of AMH / Testosterone
where is the SRY gene located
on the short arm (p)
why tissue is the genital ridges derived from
somatic mesenchymal tissue
what determines external genitalia differentiation
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
what receptors do DHT bind to
testosterone but they are more potent than testosterone
what is SRY
Sex determining region Y (SRY)
switches on during development
if it does not switch on - ovaries develop
what is gonadal dysgenesis
incomplete sexual differentiation
what is
- androgen insensitivity syndrome
- 5a-reductase deficiency
- turners syndrome
- congenital adrenal hyperplasia
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
explain the HPG axis
- 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)
what is the similarity and difference of the 3 gonadatrophins
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
2 major endocrine events of puberty
- 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)
2 types of pilosebascous units
- Vellus PSU differentiate to either:
- terminal- PSU: facial hair
- APO-PSU: axillary hair - Sebacous
- large sebaceous gland
what is puberty
non reproductive —> repoductive
+
where secondary sexual characteristics develop (primary = at birth)
what is consance
smooth ordered progression of change
every child undergoes the same order of changes
but the onset/duration will vary
what typically is the first sign of puberty for girls/boys
girls: thelarche (breasts enlargement)
boys: testicular volume increasing >4ml
when does fertility ‘begin’ for boys/girls
girls: 1st year of period
boys: from beginning of puberty (as soon as HPG axis awakens because FSH—> Sertoli cells–> spermatogenesis)
2 types of precocious puberty
- 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
when is it considered delayed puberty
girls: >13yrs / >18yrs for menarche
boys: >14yrs
explain process of primordial germ cells in development of a foetus and the form they arrest in for girls until puberty
- 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
folliculogensis
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)
what is the 2-cell 2-gonadtrophin theory
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
aims of menstraul cycle
- 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
2 phases of menstraul cycle
starts from first day of bleeding
- follicular phase
- luteal phase
luteal phase ALWAYS lasts only 14days
follicular phase can vary per woman
a regular period = within 4 days difference from last period
describe whole menstraul cycle
- CL dies
- progesterone falls = HPG axis inhibition is stopped
- rise in FSH
- recruitment of antral follicles that are of the right size/respond
- they produce a lot of oestrogen
- negative feedback
- decrease in FSH
- (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 - dominant follicle produces E2
- sustained levels of E2 for 2 days (>300) causes HPG to switch back on
- 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)
- high progesterone from CL
- decrease in FSH/LH
(we expect the oocyte to have ovulated + fertilised and so prevent other follicles growing) - after 14 days, if no pregnancy, CL dies
- decrease in progesterone so cycle begins again
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
what are the 3 layers of uterus
perimetrium
myometrium –> circular/ figure of 8 spiral/ longitudinal
endometrium
what hormone determines the size of uterus
oestrogen
high oestrogen—> high proliferation /cell division –> expand
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
- endometrium releases prostaglandins
- constriction of vessels
- necrosis/hypoxia + proteolytic enzymes from necrotic tissue
- vessels dilate –> bleeding
name the parts of the uterine tube
fimbriae–> infundibulum –> ampulla –> isthmus
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