reproduction Flashcards
(109 cards)
1
Q
parts of the uterine tube
A
fundus, isthmus, ampulla, infundibulum, fimbria
2
Q
what does the ovary contain?
A
stomal matrix, smooth muscle fibres, follicles, corpora lutea, corpora albicans and surface epithelium
3
Q
3 week development of gonad
A
origin of primordial germ cells
route of migration- PGC migrate to genital ridges
4
Q
4 week development of gonad
A
mesonephric ridge
5
Q
5 week development of gonad
A
the indifferent gonad- location of primitive sex chords and primitive cords start to proliferate out. these are closely alligned to urinary system.
Male- formation of testicular capsule
female- primitive sex chords only stay in that region
6
Q
7 week development of male gonad
A
primitive sex chords proliferate into medulla; establish contact with mesoneprhic tubule; formation of testicular capsule
7
Q
7 week development of female gonad
A
primitive sex chords only in cortical region; medullary cords degenerate
8
Q
20-24 week development of male gonad
A
formation of seminiferous cords connected to the mesonephric cords and wolffian duct
9
Q
20-24 week development of female gonad
A
cortical epithelial cells enclose germ cells to form cysts –> primordial follicles
10
Q
follicle
A
cells within follicle produce steroids
folliculogenesis accompanies and supports oogenesis
11
Q
regulators of primordial to preantral follicle
A
primary- early antral follicle the growth is gonadotrophin independent
intraovarian / paracrine growth factors and cytokines are important
anti mullerian hormone (AMH) produced by granulosa cells of larger follicles and inhibits the primordial follicle recruitment
LIF and Kit-ligand promote primordial follicle growth
antral follicle
12
Q
after ovulation what happens to the follicle?
A
regression of the follicle to produce the corpus luteum and release progesterone to maintain pregnancy
13
Q
cells in primordial follicle
A
oocyte and squamous granulosa cells
14
Q
cells in preantral follicle
A
cuboidal granulosa cells, membrane propria, theca cells for steroidalgenesis and stroma
15
Q
cells in early antral follicle
A
accumulation of fluid in the granulosa
theca differentiates into the interna (steroid) and externa (protective)
basement membrane separates interior (avascular) from blood vessels
16
Q
cells in the late antral follicle
A
antrum filled with fluid
granulosa thins out
cumulus- granulosa that surrounds the oocyte
still have basement membrane separating the two layers
LH surge causes these changes
enlarged antral cavity with folicular fluid
gap junctions connect follicle cells to each other and oocyte
17
Q
oogenesis stage in the primordial follicle
A
before birth = mitosis and beginning of meiosis I (primary oocyte arrested in prophase I)
infant / child = primary oocyte arrested in prophase I
18
Q
oogenesis stage in the primary - antral follicle
A
primary oocyte arrested in prophase I
19
Q
oogenesis stage in the preovulatory mature follicle
A
meiosis I completed- haploid secondary oocyte
20
Q
oogenesis stage in the ovulated follicle
A
secondary oocyte arrested in metaphase II
meiosis II is only completed if fertilised
21
Q
what do Amh KO studies show?
A
primordials grow prematurely and depletion of primordial pool much earlier
22
Q
regulators of early antral and beyond
A
gonadotrophin dependent- FSh and LH
granulosa and theca cells acquire FSHR and LHR
inhibin- activin - follistatin axis
23
Q
follicular phase
A
estrogen dominance
24
Q
luteal phase
A
progesterone dominance to support pregnancy
25
GnRH release
pulsatile release from the hypothalamus
26
LH and FSH release and their targets
LH to the theca cells (periphery) and have more access to blood
FSH release to granulosa cells
27
feedback in the hypothalamic-pituitary-gonadal axis
the granulosa cells produce peptide hormones inhibins and activins which feedback to anterior pituitary for FSH production
28
relationship between GnRH pulse rate and production of FSh or LH
pulse = high release of LH and FSH
| continuous stream = decrease in hormones
29
activitin
increases FSH binding and FSH induced aromatisation (estrogen)
participates in androgen synthesis, enhancing action of LH in the ovary
30
follistatin
inhibites FSH release
| bidning and bioneutralisation of activin- not directly to anterior pituitary
31
inhibin
supresses FSH
| reduced by GnRH and enhanced by IGF-1
32
2 cell 2 gonadotrophin hypothesis - early antral follicles
cholesterol enters the theca cells from the blood. in the presence of LH these are converted to androgen.
androgens from theca cells enter the granulosa cells. in the presence of FSH they produce estrogen which further stimulates granulosa cell proliferation
33
role of androgens in the early antral follicle
substrates for the conversion to estrogens
act with FSH to stimulate granulosa cell proliferation and increase follicle size
stimulate aromatase activity this promoting estrogen synthesis
34
2 cell 2 gonadotrophin hypothesis- late antral
increased estrogen acts with FSH to stmulate LHR expression on granulosa cells but NOT cumululs cells
also increases LH pulses from the pituitary
LH surge---> increased production of progesterone
granulosa cells convert cholesterol into progesterone in the presence of LH
35
actions of estrogen
egg maturation and release
growth and maintenance of female reproductive tract
stimulates granulosa cell proliferation, which leads to follicle maturation
thins cervical mucous to permit sperm penetration
stimulates upwards contractions of the uterus and oviduct
growth of endometrium and myometrium
induces synthesis of endometrial progesterone receptors
36
role of progesterone
prepares a suitable environment for nourishmtne of a developing embryo/fetus
promotes formation of a thick mucous plug in cervical canal
inhibits hypothalamic GnRH and gonadotrophin secretion
37
transports of ovarian steroid hormone in plasma
steroids are hydrophobic and require transport molecules
once unbound can freely diffuse into cell and bind to receptors
binding proteins = albumin, sex hormone binding globulin
38
FSH and LH throughout the female life course
baby = higher FSh than LH
| reproductive years = higher Lh than FSH
39
ovulation requires the coordination of many events
gene expression regulated by progesterone receptor
require vascular remodelling to increase permeability
proteases become active- model ECM
smooth muscle contraction - thinning of the wall
COC expansion- allows the oocyte to complete maturation
cumular cells adopt adhesive and migratory behaviour in response to LH
inflammatory response- why vascular remodelling is important
40
smooth muscle contraction and apical wall thinning
less granulosa cells along the wall
smooth muscle contractions allow layer to be broken down by proteases
EDN2 produced by granulosa cells- diffuses into theca layer where smooth muscle cells are found (externa). they contract and protude follicle forward
41
follicle wall structural changes from preantral to preovulatory
antral has large granulosa layers
have avariety of ECM proteins- collagen, laminin and fibronectin
lost basement membrane in the preovuatory
most surface epithelium is sloughed away
less granulosa- egg now has access to ECM proteins
42
proteolytic activity in the preovulatory follicle
produced from granulosa or invading immune cells
allow invagination of theca cells into follicle and provide nutrients from blood supply
include matrix metallo proteinases (MMPs), plasminogen activators, cathepsin L, ADAMTS1
43
which protease KO models don't ovulate?
ADAMTS1
required for structural remodelling of the basal region of preovulatory follicles/theca invagination
KO= no invagination, basement membane remains intact
regulated by progesterone
44
ADAMTS1
progesterone receptor
| link between this recepetor and remodelling of ECM
45
cumulus expansion
LH surge initiates an intrafollicular signalling cascade which converge on cumulus cells via GCs
EGF-like ligans most important for expansion
cumular cells are pushed out away from oocyte- lose connection
HA strands produced by cumular cells and form matrix
46
versican
substrate for ADAMTS1 to cells can move further away
47
oocyte secreted factors
GDF9, BMP15
acts on SMAD2/3 and MAPK to increase oocyte quality and increase embryo development and fetal viability
bidirectional signalling betwen oocyte and follicle cells
regulate cumular cell function
transzonal projections (gap junctions) connect CCs to oocyte via zona pellucida; also CC-CC
cAMP inhibits meiosis
cGMP stops enzyme from breaking down cAMP
48
LH and cumular cells
breakdown in connections between cumular cells and oocyte
| decrease in cAMP and cGMP wihtin oocyte and therefore resumption of meiosis
49
resumption of meiosis in the preovulatory oocyte
arrested in MII
decrease in cAMP and meoisis resumes to form a haploid secondary oocyte and is arrested in metaphse II until fertilisation
50
COC activation
treat with LH and cumular cells have projection and move away
granulosa cells dont become migratory only cumular cells
closer to ovulation increases their abiliyt to migrate
after ovulation decreases their ability to migrate
unexpanded COC dont bind to membrane very well
51
vascular remodelling
early follicles don't need vascular remodelling, as factors they requires diffuse in from small capillaries in the ovary
large follicles need vascularisation remodelling to supply them with what they need for growth
angiogenesis and blood flow peak during ovulation and luteinisation
factors such as VEGF are produced by granulosa cells to increase vascular growth and permability via VEGFR-2 allows the factors to get in
52
immune cell infilitration and activation in oocyte
increased vasodilation and permeability due to histamine and mast cells
may immune cell types in follicle
get in because basement membrane is getting broken down
driven by prostagladnins from PTGS2 in granulosa cells due to LH surge
53
2 isoforms of progesterone receptor
PGRA in ovary
| PGRB in uterus
54
PGR
exerts pleiotrophic control over many reproductive processes
- neuroendocrine gonadotrophin regulation
uterine decidualisation
mammary galnd development
ovulation
55
PRLACZ mouse
LacZ reporter gene into promoter region of PGR
56
PGR expression
higly expressed in granulosa cells
transiently expressed to do with ovulation
only in mural granulosa cells, not in cumular cells
57
PGR KO mouse
anovulatory
| defect in release - oocytes are trapped in the follicle
58
PGR regulated genes in the ovary
ADAMTS1 is essential for remodelling of the follicle wall
| defects in cumulus expansion
59
ovarian transplant experiment
PGR within ovary is important regulatory for ovulation
- WT ovary in WT ovary = normal
- KO ovary in WT ovary = didn't restore function at all, no ovulation
- KO transplant mated to WT produced no pups
WT ovary mated to WT male produced pups
60
PCOS
disrupted cycle and ovulation
polycystic ovaries- follicles develop to late antral phase, then arrest
hyperandrogensism
61
androgens and PCOS
androgen excess
62
experiment androgens and PCOS
four treatments
prenatal DHT (doesn't convert to estrogen)
postnatal DHT
postnatal DHEA (precursor to androgens)
letrozole (prevents androgen to estrogen)
post natal DHT condition has the most traits simialr to PCOS and arrested follicles
63
Androgen Receptor KO models to determine role of AR
use flox and cre
| causes subfertility, dysfunctional ovulation, abnormal folliclar development and defective neuroendocrine control
64
does androgen excess initate the development of PCOS via intra or extra ovarian AR-mediated mechanisms?
extra-ovarian - brain specific loss of AR signalling
intra-ovarian - granulose cell specific loss of AR signalling
if PCOS is not observed then AR signalling is required
therfore AR signalling within the brain, not ovary is a major mediator in PCOS development
65
testic migration during development
10-15 weeks - pelvic position, suspensory ligaments and regresses
25-28 weeks- migrates over pubic bone , reaches scrotum by 35-40 weeks
66
cremaster muscle
allows the sac to be withdrawn closer or further away
67
dartos muscle
wrinkles skin on scortum and decreases SA to control temperature
68
structure of testis
highly convoluted tubules to increase SA and increase sperm production
covered by thick connective tissue capsule - tunica albuginea
rete testis- labyrinth of tubules within mediastinum, drains to the head of the epididymis via efferent ductules
69
functional compartments of testis
intratubular compartment
- contains the sertoli cells
- sperm production
- seminiferous tubules
peritubular compartment
- neuronal and vascular elements
- leydig cells
- steroid production
70
adult seminiferous tubules
```
not homogenous
differnt types of cells
complex stratified epithelium
sertoli cells have sperm embedded in them
both mitosis and meiosis occurs
```
71
maturation of spermatogonia
spermatogonia --> spermatocytes --> spermatids --> spermatozoa
72
sertoli cells
columnar epithelial cells
provide structural organisation
connected by tight junctions - BLOOD TESTIS BARRIER
73
sertoli cell blood testis barrier
interstitial and basal compartments are separated by a cellular basement membrane
protects the sperm from damage from any toxins in the blood
spermatogonium is in close contact to eh peritubular region and blood. however just above that is the tight junctions which are protecting the more mature cels closer to the lumen. also protectin the sperm cells themselves because if they were to get into the blood they would produce antigens against the mature sperm which would have consequences for the fertilty of the male
74
sertoli functions
supportive -nursing'
exocrine- fluid production to move immobile sperm out of testis towards the epididymis
endocrine- androgen binding protein procution, androgen receptor and FSh receptor ecpression
aromatisation of testosterone to estradial
75
spermatogensis vs spermiogenesis
spermatogenesis:
1. mitotic proliferation
2. meiotic division - diversity
3. cytodifferentiation (SPERMIOGENESIS), package of the chromosomes for effective delivery to the oocyte round cells change to elongated sperm- packaged in a way for effective delivery. acrosome reaction
76
spermatozoan structure
head- condensed nucleus, acrosome
midpiece- mitochondria, provide energy for ATp
tail- fibrous sheath
77
organisation of spermatogenesis
temporally and spatially
rounds are initiated at time interveals that are constant and characteristics for each species
4 successive waves occur at the same time
human cycle = 16 days apart
adjacent segments of tubule are ither advanced to just behind
78
steroid production in the testis
NO POSITIzVE FEEDBACK
LH and FSH from ant pituitary
- LH acts on Leydig cell --> androgens
- FSH acts on the sertoli cell --> androgen binding protein, spermatogenesis
79
castrate male
removal of the testis- LH levels are higher than intact because there is no negative feedback from leydig and sertoli cells
80
estrogen in males
increase with age
negative feedback to the hypothalamus and pituitary
synthesied in leydig cells, sertoli cells, germ cells and sperm
81
activin male
androgen synthesis enhancing LH action in testis
| enhanced spermatogenesis and is elevated int he epididymis and vas deferens
82
follistatin in male
inhibits activin activity
| increases progressively from the testis to distal vas deferens
83
inhibin male
highly expressed in epidiymis and testis and regulates spermatogensis
secreted in sertoli cells
androgens stimualte inhibin production
84
spermatogenesis is dependent on endocrine support
surgical removal of pituitary = testicular shrinkage, declinei n sperm output, arrest in spermatogenesis
leydig cells become involuted, testosterone output falls and testosterone dependent male genetalia hypotrophy
LH controls Leydig cells!!!
85
sertoli receptors
androgen receptors - bind androgens and generate even more potent androgens than testosterone alone via 5alpha reductase activity
FSH stimulate expression of androgen receptors, inhibin ,activin and androgen binding protein
acts indirectly on spermatogenesis
86
Leydig cells
convert lipids to testosterone
87
steroidogenesis in the testis
leydig cell is the primary producer of steroids in the male
leydig cell releases testosterone, androstenedione and DHEA
these enter the sertoli cells and bind to ARs and convert to more potent DHT
88
actios of testosterone
spermatogenesis
development of male physical and behavioural characteristics
gametogenesis
maintenance of reproductive tract and production of semen
maintains blood testis barrier
accessory gland function
89
high E2 - follicluar phase
increase in cilia beat frequency
| smooth muscle contractions
90
high P4 phase
deciliation of cells
| smooth muscle relaxation - therefore zygote is trappe at junction until the muscles relax and it moves into isthmus
91
sperm maturation
maturation in the epididymis
| - DNA stabilisation, chromatin condensation, concentration
92
sperm storage
in vas eferneces before ejaculation in seminal fluid
93
accessory glands in males
```
seminal vesicles
- alkaline fluid, fructose (energy)
- energy/ muscular contractions in female tract
prostrate
- alkaline fluid, enhances sperm motility
antimicrobieal effects
bulbourethral glands
- mucous secretion - lubrication
```
94
seminal plasma
creation of alkaline environemnt in the vagina
coating the sperm cells with capacitation inhibitors- dont want sperm to start being degraded
activation of sperm
fluidizing ejaculate after 15-20 minutes (proteases from prostrate) so sperm can move within female tract
95
corpus cavernosum
engorgement of erectile tissue with blood --> erection
96
ejaculation
rhythmic contraction of vas deferens
97
sperm movement and maturation in female tract
ejaculate deposited in vagina at cervical os
fluidises after 15-20 minutes
uterus provide nutrients, physical mucous consistency and aid capacitation
ocoyte attracts sperm
- chemoattactant via odorant receptors
- progesterone produced by cumulus cells and progesterone receptors on sperm head
98
role of oviduct in sperm transport and maturation
formation of a holding reservoir i n the isthmus - so sperm can complete capacitation
binds ejactulated sperm to the epithelium
99
seminal fluid in oviduct
quality of seminal fluid impacts on future health of the baby
interacts with female tract- promotes an immuno-tolerant environment so mother's immune system doesn't attack foreign thing
100
capacitation
stripping of non-coalvently bound epidydiymal and seminal glycoproteins and sterols
decrease sperm plasma membrane stability and increase calcium permeability to increase cAMP
increased motility
female reproduction tract ideal for process due to proteolytic enzymes and high ionic strength
media supplemented with H2O2 assists with in vitro capcitation
101
acrosme reactions
initiated by sperm contactin the zona pellucida
acrosome swells
acrosome contents are exocytosed, includes proteolytic enzymes
acquires potential to fuse tih oocyte plasma membrane
hyaluronidase assists sperm through cumulus matrix
cortical granulase fuse to egg palsma membrane and undergo exocytosis - prevents polyspermy
102
zone pellucida glycoproteins
acellular glycoprotein coat
synthesised and secreted by oocyte in primary follicle
ZP3 allows specieis specific sperm-oocyte bidning
ZP3 target for immunocontraception - can induce a resposne against ZP3 agprotein in egg for pests
103
fertilisation
binding of 1 capacitated perm to ZP2/3 induces acroseom reaction
penetrates ZP to the perivitelline space
binds to a fuses with the oolema via fertilin-intgerin adhesion; activated calcium waves
calicum induces realse of cortical granules and resumption of meiosis; formation of asymmetrically located cleavage furrow
meiotic division completed
- 2nd polar body and female pronucleus
formation of male pronucleus
104
calcium spiking pattern in a fertilised oocyte
starts a few minutes after fusion
terminated at pronuclear stage
trigger the resumption of meiosis- oocyte activation, trigger release of cortical granules
gardeing of zona pellucida- zona reaction, prvenets polyspermy
preservation of euploidy- even nunber of chromosoems
105
syngamy
formation of zygote
4-7 hours post fertilisation
fusion of male and female pronuclei
106
contributions to zygote from male and female
male = centrosome, spindle formation
| female- cell membanre, cytoplasm, organells, mitochondria
107
preimplantation embryo
size of embryo does't change but the blastomeres get smaller
108
genetic activity in preimplantation embryo
first few cleavages rely on stored maternal mRNA and proteins
at 4- cell stage = wave of maternal mRNA degradation that destroys much of maternally inherited mRNA
improinting of DNA and or chromatin proteins such as histones
epigenetic process of inhertinace
109
energy metabolism in preimplantaiton embryos
cleavage stage = pyruvate --> lactate for energy
| compactino stage = glucose
