Ovulation and Fertilization Flashcards
Granulosa Cell Cohorts of Graafian Follicle
GCs
- closest to basement mem
- majority are mem bound
- acquire LH R
- not released during ovulation
Mural GCs
- preantral cells that line antrum
- released @ ovulation
- high FSH R levels
Cumulus Granulosa Cells
- surround oocyte
- expand just before ovulation
Cumulus Granulosa Cells
paracrine signaling
allow exhange of small molecs, glucose metabolites & ions b/t cumulus cells & oocyte
Required for cumulus expansion (remodeling & expansion of matrix surrounding cumulus cells)
Up reg connexins required for oocyte competence
Pre Ovulatory Changes & Oocyte competence
Oocyte competence- ability of oocyte to complete maturation, undergo fertilization & reach blastocyst stage
Communication pathways w/in dominant follicle
- theca cells-granulosa cells
- granulosa- granulosa
- oocyte-cumulus granulosa cells (oocyte cumulus cell complex OCCC)
Summary of Dominant Follicle
FSH leads to fluid accumulation
Folicular fluid= antrum expansion
increase FSH sensitivity
Increase LH response
Decreace AMH
High TGFs
Hormonal Changes
Large rise in estradiol E2
- 48-96 hrs before ovulation
- feedback on HP axis
- will not ovulate if <25 mm; 18-23 mm ideal
LH surge
- 30-36 hr windown
- peak 10-12 hr before ovulation
- LH acts directly on theca & granulosa cells to stim progesterone prodution
- stim resumption of meiosis I & extrusion of 1st polar body
FSH surge
- inhibin B levels drop
- Activin rise
LH & FSH Effects on Oocyte= GVBD Breakdown
Germinal Vesicle Breakdown - nuclear mem breakdown
- Disrupts gap junctions b/t cumulus cells & oocyte- no LH/FSH R on oocyte
- cAMP levels drop in oocyte
- loss of gap junctions & fall in cAMP stimulate Ca2+ release
- transient Ca2+ w/in oocyte- from ER, incrase intracell, in oscillations, increase in free Ca2+= meiotic resumption.
Relates back to follicular steroidogensis where GC releases progesterone under FSH & LH effect. Production of progesterone & LH surge= ovulation.
Mucification
secretion of hyaluronan
- induced by FSH & LH
- secreted by cumulus cells
- major component of ECM
- primary glue keeping OCCC intact
- rapid expansion of OCCC
- required for subsequent fertilization
Expansion of OCCC/mucification
LH & Graafian
Increase COX2
- stimulate PGE2 & F2 a
- PGE2 binds to EP1 R on granulosa & theca cells= directs site of follicle wall breakdwon
Increase matrix metalloproteinases MMPs
- MMP-1.2,9
- most active on BL & w/in GC matrix
- frees mural GCs & OCCC
FSH & Graafian Follicle
Increased production of plasminogen activator- serine protease
- increase active plasmin
- fibrinolysis of follicular wall
Increased production of VEGF
- FSH stimulated
- estradiol stim VEGF & VEGF R
- progesterone stim VEGF
High FSH, estradiol & progesterone increase VEGF production
Endothelins & Ovulation
Endothelin
- 21 aa
- ET 1,2,3
- potent vasoconstrictors
- ET R= GPCR
- ET R antagonists= for pulm hyperT
- induce smooth m. contraction:
- on cells surrounding follicle
- on ovarian surface
- shortens layer around follicle- fibrinolysis
Ovulation
Release of proteolytic enz that act in a very specific site in the follicle
Follicle looses all of the fluid , OCCC & mural granulosa cell
Very small portion of tissue is lost
Stages of Penile Erection
1- initial filling, psychological/sexual stimuli
2- tumescence/ partial erection, increase blood flow to penis to elongate & expand.
3- full erection, dilatation, trapping blood compression of v. , stretching tunica, increase in PO2 & intracavernous P
4- rigid erection, maximum, contraction of ischiocavernosus m., penile v. are forecefully compressed, emission & ejaculation
5- return to flaccid, detumescence, m. contraction to increase outflow, decreased lenght & flaccidity
Orgasm
Orgasm
Stimulation of female genitals lead to different activation patterns in brain
Due to diff innervations
Neurophys of Sexual Response
Inhibitory=
- SE
- PRL
- Opiods
- Endocanabinoids
- TRH
Stimulatory=
- sex steroids
- DA
- oxytocin
- NE
- melanocortin
Ovulatory Window changes
- increased vaginal secretions- during intercourse
- enhance lubrication
- stim sperm transport
- secretions increase semen loss due to flowback
- acid content liquifies sperm
- cervical mucus
- decreased viscosity
- facilitate sperm transport through cervical os
- cilia of uterine tube epith
- coordinated beat freq
- act as syncytium to facilitate gamete transport
- myometrium & uterine tube
- rhythmic contractility
- stim gamete transport in both dir
- enhance fluid movement
- stim sperm transport
- contractility will be completely suppressed w/ rising progesterone
Sperm transport through reproductive tract
sperm deposited into ant vagina & transported through cervical os
Majority of sperm deposited 99% are lost due to flowback
50 million in ejaculate
100,000 will reach uterine cavity
50-100 reach fallopian tube
Uterotubal Junction
Mucins in cervical os guide sperm through cervix
Health normal sperm less than 1- min to pass through uterine cavity
Uterotubal junction represents last barrier= have viscous mucus there
Fallopian Tube
Oviduct fluid doesn’t have immune cells
Fertilization Prep
- Capacitation- f maturation of sperm
- increase in mem fluidity
- change in swimming pattern to hyperactivity
- hyperactivation
- increased motility & E
- required for sperm to swim through oviduct mucus
- required to penetrate OCCC & matrix
- Chemotaxis
* sperm are attracted to egg
Hyaluronidase
released by sperm
enz degrading hyaluronan
degrades cumulus-cell matrix of OCCC
required for sperm to reach ZP
Degradation of matrix permits for increased tail whip, resulting in max penetration
Acrosome Rxn
When sperm contacts ZP & interacts with ZP glycoproteins- bind w/ ZP3
acrosin- serine protease that hydrolyzes ZP
Penetration
Penetration= when sperm passes through ZP to perivitellin space
Large rise in Ca2+ i that causes cortical rxn
Cortical Rxn
wave like release of cortical granules into perivitellin space
cortical granules contain enz that effectively alter ZP
These granules inhibit additional sperm from binding to ZP- referred to polyspermy block
2nd Polar Body
large rise in Ca2+ i & cortical rxn induce oocyte activation (so oocyte completes meiosis II)
This extrudes 2nd polar body
