Aug30 M1-Oocyte Development Flashcards
2 phases of oocyte growth and maturation
- growth (3 months): primordial to fully grown with GCs and ZP. (primordial to pre-antral follicle)
- meiotic maturation, pre-ovulatory (36 hours = between LH surge and ovulation). FSH and LH (LH also responsible for the surge and the ovulation) are the hormones that triggers step 2 (antral follicle to ovulation)
primordial follicle charact
oocyte + surrounding GCs (somatic ovarian cells)
primary follicle charact
GCs increase in number to keep enclosing oocyte as it grows. give it molecules
secondary follicle charact
inside to outside
- oocyte
- GCs
- basement membrane
- theca cells
function of GCs and theca in secondary follicle
make estrogen
- theca makes androstenedione bc of LH infl
- GCs make estradiol (from androstenedione) using aromatase enzyme bc of FSH infl
early antral follicle is what
follicle with an antrum (cavity filled with fluid produced by GCs in between layers of GCs)
last step of growth phase
early antral follicle layers
inside to outside
- oocyte
- cumulus granulosa
- antrum
- mural granulosa
- BM
- theca cells
late antral follicle charact
- like early but more GC layers
- is the Graafian follicle
- is the dominant follicle that will be ovulated
- beginning of maturation, ovulation phase*
reserve oocytes in the ovary means what
oocytes that didn’t enter the growth phase yet
when did an ovulated oocyte start its growth phase
3-4 months before ovulation
when do oocytes enter the growth phase
constantly have oocytes entering growth phase
general concept of growth signaling between cells
-GF secreted by cell
1 interacts with an RTK on cell 2
-cell 2 activates a signaling pathway
-cell 2 increases prot synth
how GCs tell oocyte to grow
- GCs produce the KIT ligand (KITL)
- KITL binds Rs on oocyte
- oocyte increases prot synthesis and gets bigger
why not all follicles grow because of signals from granulosa cells
because of ovary architecture, not all follicles and oocytes can grow simultaneously
2 reasons why oocyte has to grow a lot
- after fertilization, will undergo many divisions without preceding cell growth, to form a blastomere
- during growth, accumulate factors (prot, RNA) needed for embryo to feed itself in week 1 (before implantation)
other role of GCs in growth of oocytes than telling them to grow
transfer to them the nutrients necessary for growth via gap junctions (adjacent channels forming holes in memb)
molecules passing in gap junctions from GC to oocyte
- aa
- small molecules
- pyruvate
- cholesterol
- nts (during meiotic maturation, triggered by EGF-like molecules of mural GCs binding EGF-Rs on mural and cumulus GCs)
gene of gap junctions between GCs and oocyte + KO consequence
- GJA4
- KO = oocyte 75% of normal size + can’t undergo meiotic maturation
zona pellucida is what
coat of glycoproteins made by oocyte surrounding it
2 fcts of ZP
- block 2nd sperm from fertilizing oocyte (chemically modified after fert)
- protect embryo before implant
how GCs reach oocyte and make gap junctions through the ZP
send transzonal projections (tube, foot with actin)
what triggers the transfer of nutrients from GCs to oocytes
oocytes themselves, have to tell GCs to do it
-secrete 3 molecules (GDF9, BMP15, FGF8B) that go on GC Rs.
what happens in the follicular phase of the menstrual cycle
many follicles complete the last two weeks of the growth phase to reach the early antral stage. many will die after that
pre-ovulatory phase (meiotic maturation) depends on what hormone
FSH (without it = only reach early antral stage)
what happens mid-cycle to the follicles that reached the early (pre) antral stage
- One follicle catches most of the FSH and becomes dominant. It makes more estradiol that shuts down the pit from making FSH. the GCs of the dominant follicle prolif.
- all other pre antral follicles get little FSH bc of that (FSH inhib in pit bc of dominant’s estrogen) and become atretic or remain for next cycle
goal of daily FSH injections in infertile women (assisted reproduction)
- enables all follicles to go from pre-antral stage to ovulatory
- more follicles can make eggs now
why chemo causes infertility (2 reasons, theories)
- attacks dividing, developing follicles die, reserve replaces them and reserve empties
- attacks dividing cells AND primordial follicles directly
meiotic divisions during the meiotic maturation
- beginning = meiosis not started
- undergoes first div (including metaphase 1) and gives polar body
- continues meiosis until metaphase 2
polar body def
daughter cell of maturing oocyte that is a dead end, results from spindle of metaphase 1 on extremity of cell. contains half chromosomes but useless
reason for most trisomies
errors in metaphase 1 (more) and metaphase 2 (also) of meiotic maturation of OOCYTES
prob of error goes up a lot after 35
FSH is necessary to complete meiotic maturation but what is the essential trigger for beginning of meiotic maturation
LH
how LH triggers meiotic maturation
- comes from pituitary (surge)
- binds Rs on mural GCs
- mural GCs produce epidermal growth factor-like molecules (not EGFs) that can bind EGF-Rs that are on mural and cumulus GCs
- mural and cumulus GCs receive EGF-like molecules from mural GCs on their EGF-Rs and this affects the level of cyclic nucleotides and regulates maturation
broad role of LH in triggering meiotic maturation
BREAKS a signaling cascade (mural GCs to cumulus GCs. these then make a lot of cGMP which goes in oocyte via gup junctions, inhibits PDE3A in oocyte and, since PDE3A lowers cAMP, cAMP in oocyte remains high) that causes high cAMP in the oocyte and INHIBITS maturation
after mural GCs bind LH with their LH GC Rs, and make EGF-like molecules that bind EGF-R on cumulus GCs, what happens to trigger maturation
- this binding inhibits cGMP in the cumulus GCs.
- PDEA3 (phosphodiesterase A3) in oocyte no longer inhibited
- cAMP goes down in oocyte bc of PDEA3 reducing it (now active)
- maturation starts
steps of meiotic maturation other than chromosomal changes (cytoplasmic)
- redistribution of mts
- redistribution of ER
- accum of cortical granules at cortex
- changes in prot synthesis
- start of degradation of oocyte mRNA (maternal)
how to trigger meiotic maturation without LH
- put cumulus GCs and oocyte alone in culture
- signaling from mural GCs to increase cumulus GCs’ cGMP is absent
- so can grow and fertilize oocytes in vitro*
one way to get oogonial stem cells experimentally even though we’re not sure these exist in the ovaries
use embryonic stem cells and induced pluripotent stem cells
