R for OT & PGF/PGE up regulated Ion channels activated Connexin 43 increase gap junctions contractility

FP GPCR smooth m. contraction vasoconstriction vasuclar smooth m. hypertrophy stim Ca2+ mobilization OTR smooth m. contraction inhibited by progesterone mRNA up reg by estradiol stim Ca2+ mobilization

EP1 & EP3 smooth m. contraction vasoconstriction EP1 Ca2+ mobilization EP3 decrease cAMP in upper fundus EP2 &EP4 smooth m. relax vasodilation stim adenylate cyclase stim cAMP production on the cervicx

Parturition & Lactation Flashcards by Esty Sherman

Phase 1 Quiescence

prelude to birth

2nd trimester & 1st part of 3rd trimester

Uterine quiescence

No contractility

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Phase 2 activation

R for OT & PGF/PGE up regulated

Ion channels activated

Connexin 43 increase

gap junctions
contractility

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Phase 3 Stimulation

labor & birth

contractions

cervical dilation

delivery of fetus & placenta

Myometrium responds to uterotropic agents, oxytocin & PGs

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Phase 4 Involution

Recovery

Facilitated by OT

delivery of placenta results in rapid hormone withdrawal

Uterine involution & cervical repair

Postpartum

lactation
depression

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Uterine Activity Regulation

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Oxytocin OT

Potent uterotonic agent

OT induced uterine contractions identical to endogenous ones

Uterine contractions can be induced w/ electrical stim of post pit or manual stim of nipple

OT R antagonist- competitive Inhibit labor

Atosiban inhibit preterm labor

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Myotmetrial response to OT

Increase sensitivity to OT with increase gestation time

Changes to myometrial OT R

Up reg OT R prior to parturition

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PG & parturition

COX inhibitors- inhibit myometrial contractility

Exogenous delivery of PGF2a & PGE2 stimulates uterine contractility in women

PG increase during labor!

COX2 upreg in myometrium & cervix just prior to parturition

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FP & OTR

GPCR
smooth m. contraction
vasoconstriction
vasuclar smooth m. hypertrophy
stim Ca2+ mobilization

OTR

smooth m. contraction
inhibited by progesterone
mRNA up reg by estradiol
stim Ca2+ mobilization

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EP R

EP1 & EP3

smooth m. contraction
vasoconstriction
EP1 Ca2+ mobilization
EP3 decrease cAMP
in upper fundus

EP2 &EP4

smooth m. relax
vasodilation
stim adenylate cyclase
stim cAMP production
on the cervicx

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Pre term uterus- quiescence

PGE2 & progesterone

relax tone
inhibit contractions
PR
high EP2 R esp in JZ
low EP1/EP3

Mem bound PR

PGRMCs
high in JZ

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Term uterus

Fundus & upper segments

decrease/loss PR
decrease/loss mPR
up reg OTR

Lower seg

slight increase in OTR

Cervix

no OTR

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Term uterus

Outer myometrium

up reg FP

fundus

up reg EP3
up reg FP

upper seg

up reg EP3
up reg FP

Lower seg & cervix

up reg EP4 & high level EP2
lower FP level

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Amnion & Fetus contribute to contractility

EP1, EP3 & FP are up reg in amnion during labor

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Contractile F & R gradient

smooth m. contractile OTR, FP & EP3 R are highest in fundus & upper seg of uterus

Strong contractions

Smooth m. relaxant EP2/EP4 are higest in lower seg & cervix.

Relaxation

Strong contractions initiated in fundus & radiate to cervix.

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Parturition requires uterine relaxation

myometrium must relax between contractions

tonic prolonged contraction can cause uterine tetany= life threatening to fetus

As labor progress

increase OT & PGF
increase contraction intensity
decrease relaxation

Net= increased contractile F & decreased time between contractions

Summary

PGF2 augments OT action

PGF binds to FP to cause intense smooth m. contractions throughout entire uterine body

PGF2 stim paracrine OT production

PGE contributes to smooth m. contraction, by binding to EP3 R in uterine fundus & EP1/EP3 R on amnion

PGE2 binds to EP2 R throughout uterus to reg smooth m. relaxation

PGE2 binds to EP2 & EP4 to stim relaxation of lower seg of uterus & cause relax & dilation of cervix!

Increase estrogen may induce parturition

localized E:P ratio shift @ end of gestation in favor of estrogen

stim formation of myometrial gap junctions

stim PGF2a & PGE2 production

stim OT production

stim upreg of myometrial OT R

stim cervical ripening

Intrauterine hormone

OT & PRL stim enz activity in decidual cells

increase hydrolysis of estrone sulfate in fetal mem

Together lead to increase production of locally acting intrauterine estrogens

local effects

changes due to increase local [] of estrogen

Localized progesterone withdrawal

Progesterone decreases myometrial tone, increased cervical rigidity & blocks OT R

Decrease in progesterone favors myometrial activation

Progesterone withdra permits for myometrial contractions & cervical ripening

Increase PGF2a & PGE2 production

Stim upreg of MMPs - breakdown of cervical plug

MMPs

Ovary, release OCCC & fibrinolysis of follicle wall

Endometrium, breakdwn functionalis & vascular remodeling

Endometerium, invasion & vascular remodel

cervix. dilation & ripening

Labor & Delivery

childbirth period of onset of regular uterine contractions until expulsion of placenta

Stage 1 labor

Latent phase

reg uterine contractions that bring dilation of cervix (2-4 cm)
Epidural

Active

rapid change in dilation to 10 cm

Stage 2 of labor

starts when cervix is fully dilated to delivery of infant

increase in bloody show

desire to push

pressure on rectum

onset of nausea & vomiting

Ferguson Reflex

increase in uterine stretch cervical P trigger neuroendocrine response + OT feedback loop b/t uterus & post pit Loop creates increasing levles of both local OT & systemic Increase in OT stim production of more OT R Until placenta delivered

Stage 3 of labor

after delivery of infant- to separation & delivery of placenta major complication is maternal hemorrhagin

Postpartum changes

6-8 wks after delivery 4-6 months Shivering Uterine involution- 6-8 wks normal size Cervix slightly dilated for 1 wk- returns to baseline 12-16 wks Vaginal tone may or may not return to baseline Av 13 lb weight loss After 3 monhts PRL will return to normal and FSH & LH (if breastfeeding) If not breasfeeding, PRL returns to normal 1-2 wks but no fertility until 3 monhts due to anatomy remodeling

Hormones Postpartum

hCG- 2-4 wks non pregnant FSH/LH- low for 2-3 wks after delivery Ovarian- low until FSH/LH stabilize Menstruation by 12th week

hPL

appears to stim mammogensis binds to PRL to stim breast dev

Stage 1 lactogenesis

2nd half of preg secretory initiation mammary gland secrete milk lactose, protein & immunglobin [] rise high progesterone suppresses milk secretion colostrum

Progesterone & lactogenesis

acts on breast PRL suppression of upreg Block lactogenesis PRL elevated but can't stim lactogensis Estrogen stim alveoli & duct deve Estrogen stimulates colostrum

Lactation

humoral & neuroendocrine mech reg lactation & milk let down are complex Repetitive breasfeeding stim milk prod (+ feedback sys) Lactogenesis requires PRL which is primary hormone associated w/ lactation. Insulin, glucocorticoids (cortisol) GH & IGFs involved Milk ejection dep on physical stimulus of suckling & OT (PRL prod) \*reg by many factors like emotional & visual\*

Stage 2 lactogenesis

onset of copious milk production secretory activation typically starts 2-3 days after delivery but may take 1 week Progesterone withdrawal leads to onset of copious milk secretion Blood flow, O2 & gluc uptake increase Progesterone withdrwal & loss of PR in breast tissue permit PRL action Maternal secretion of insulin, GH, cortisol, PTH facilitate nutrient mobilization required for milk Breasts swell

PRL

After 12 weeks: PRL levels still increase immed after feeding As daily feedings are red, PRL levels may fall to pre preg levels b/t feedings

Milk production- suckling reflex arc stim PRL

suckling stim hypothal nuclei TIDA neurosn inhibited & DA secretion red increase PRL PRL acts directly on alveolar epith cells to stim milk production

Milk Ejection- suckling reflex arch releases OT

sucking stim hypothal nuke triggers increased release of OT from post pit Increase levels of OT act on myoepith cells lining mammary alveoli leads to contraction of mammary alveoli & milk ejection

Breastfeeding difficulties

Milk letdown problems 1. imparied milk ejection- imparied OT release: * cause egorged breasts * leads to suckling problems * plugged milk ducts * mastitis 2. psychological diff * psopartum depression/stress/irritability * lack of visual stimuli