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
