Parturition II Flashcards
Characteristics of smooth muscle
Shortening with contractions
Forces in multiple directions
Not organized as skeletal muscle
Greater multidirectional force
The interaction of myosin and actin activates
ATPase which hydrolyses ATP and generate force
Uterine relaxation
Maintained by
Increase Myocyte cAMP
Uterine relaxation
Activates protein kinase A to promote phosphodiesterase activity with de phosphorylation of
Myosin light chain kinase
Actin assumes a fibrillar form, and calcium enters the cell to combine with calmodulin to form complexes.
Uterine contraction
The complexes activate MLCK to bring about the phosphorylation of the myosin light chains
Uterine contraction
Generates ATPase activity to cause sliding of myosin over the actin fibrils, which is a uterine contractor
Uterine contraction
Agents that promote contraction act on myometrial cells to increase intracellular cytosolic calcium concentration.
Intracellular calcium
Conditions that decrease calcium and increase intracellular concentration of cAMP and cGMP ordinarily promote
Uterine contraction
Cellular signals that control myometrial contraction and relaxation can effectively transferred between cells through intercellular junctional channels
Myometrial gap junction
Proteins of gap junction
Connexon 1 and 2
Cell surface receptors
Categorized into 3
G protein linked - activate phospholipase C
Ion channel linked
Enzyme linked
Cell surface receptors are transferred to the uterus by either
Endocrine- via maternal blood
Paracrine - near target cell
Autocrine - itself
Phase 1
Uterine quiescence and cervical competence
Phase 1 Uterine Quiescence and Cervical Competnce
Factors
Estrogen and progesterone
Increase in cAMP
Generation of cGMP
Modification of myometrial cell ion channels
Phase 1 Uterine Quiescence and Cervical Competnce
Components of a broader based molecular system that implements and maintains uterine quiescence.
Progesterone
Estrogen
Phase 1 Uterine Quiescence and Cervical Competnce
Inhibit parturition
Maintains uterine quiescence by various mechanism that cause decreased expression of the contraction associated proteins (prostaglandin, oxytocin, connexin)
Progesterone
Phase 1 Uterine Quiescence and Cervical Competnce
Directly precedes progression of phase 1 into phase 2 of parturition
Pretogestrone withdrawal
Phase 1 Uterine Quiescence and Cervical Competnce
Promote parturition
Estrogen
Phase 1 Uterine Quiescence and Cervical Competence
Would promote myometrial gap junction thereby, promoting uterine contraction
Estrogen
Phase 1 Uterine Quiescence and Cervical Competnce
A number are associated with Gas mediated activation of adenyl cyclase and increased levels of cAMO are present in myometrium
G protein Coupled Receptors
Phase 1 Uterine Quiescence and Cervical Competnc
Mediate gas stimulated increases in adenylyl cyclase, increased levels of cAMP, and myometrial cell relaxation
Beta adrenoreceptors
Phase 1 Uterine Quiescence and Cervical Competnce
Has been demonstrated in myometrial smooth muscle and blood vessels.
LH and HCG receptors
Phase 1 Uterine Quiescence and Cervical Competnce
Acts to activate adenyly cyclase by way of a plasma membrane receptors Gas linked system
Chorionic gonadotropin
Phase 1 Uterine Quiescence and Cervical Competnce
This decreases contraction frequency and force and decreases the number of tissue specific myometrial cell gap junctions.
High circulating levels of HCG may be one mechanism causing quiescence
LH and HCG receptor
Phase 1 Uterine Quiescence and Cervical Competnce
Peptide hormone that is a member of insulin like GF
Relaxin
Phase 1 Uterine Quiescence and Cervical Competnce
Relaxin originate exclusively from the
Corpus luteum
Phase 1 Uterine Quiescence and Cervical Competnce
Relaxin greates amount found between
8-12 weeks gestation
Phase 1 Uterine Quiescence and Cervical Competnce
Mediates activation of adenylyl cyclase
Effect on cervical softening
Promote myometrial quiescence
Relaxin
Phase 1 Uterine Quiescence and Cervical Competnce
Synthesized in the placenta and hypothalamus
CRH
Phase 1 Uterine Quiescence and Cervical Competnce
CRn increase during the
Final 6-8 weeks of normal pregnancy
Phase 1 Uterine Quiescence and Cervical Competnce
CRH has dual effect
Utero relaxant at first
Utero contraction later
Phase 1 Uterine Quiescence and Cervical Competnce
These interact with a family of different G protein coupled receptors, several of which are expressed in myometrial
Prostaglandin
Phase 1 Uterine Quiescence and Cervical Competnce
Prostaglandin usually considered as
Uterotonins
Phase 1 Uterine Quiescence and Cervical Competnce
Prostaglandins with diverse effects
Prostacyclin E2 - relaxation
Prostacyclin F2- contraction
Phase 1 Uterine Quiescence and Cervical Competnce
Prostaglandin produced using plasma membrane derived arachidonic acid, which usually is released by the action of the
Phospholipase A2 or C
Phase 1 Uterine Quiescence and Cervical Competnce
Activation of gaunylyl cyclase increases intracellular cGMP levels, which promotes smooth muscle relaxation
ANP and BNP and cGMP
Phase 1 Uterine Quiescence and Cervical Competnce
Striking increases in the activity of enzymes that degrade or inactivate endogenously produced uterotonins
PGDH and prostaglandins Enkephalins and endothelins Oxytocinase and oxytocin Diamine oxidase and histamine Cetechol O methyl transferase and cathecolamines Angiotensinases and angiotensin II PAF acetylhydrolase and PAF
Phase 2
Uterine activation and cervical ripening
Phase 2 Uterine activation and cervical ripening
May be used to prevent preterm labor has been studied in trials
Progesterone containing injections or vaginal suppositories
Phase 2 Uterine activation and cervical ripening
Administered during the latter phase of the ovarian cycle, which induces menstruation prematurely
Mifepristone (RU-486)
Phase 2 Uterine activation and cervical ripening
Effective abortifacients in early pregnancy, not so much in the latter part
Mifepristone
Phase 2 Uterine activation and cervical ripening
Must play a central role in spontaneous labor
Oxytocin
Phase 2 Uterine activation and cervical ripening
Primary regulators of oxytocin receptor expression
Progesterone and estradiol
Phase 2 Uterine activation and cervical ripening
In vivo or in myometrial explants increases myometrial oxytocin receptor concentration,
Promote parturition
Estradiol treatment
Phase 2 Uterine activation and cervical ripening
Increase oxytocin receptor degradation and inhibit oxytocin activation at the cell surface
Inhibit parturition
Progesterone
Phase 2 Uterine activation and cervical ripening
Remodeling of the ECm of the uterus, cervix, vagina, breast and pubic symphis as well as promoting cell proliferation and inhibiting apoptosis
Relaxin
Phase 2 Uterine activation and cervical ripening
Promotes growth of the cervix, vagina, and pubic symphysis and is necessary for breast remodeling for lactation
Relaxin
Phase 2 Uterine activation and cervical ripening
Also significant more common in pregnancies complicated by hydramnios
Preterm labor
Phase 2 Uterine activation and cervical ripening
May include activation of cell surface receptors or ion channels, transmission of signals through ECM or release of Autocrine molecules that act directly on myometrium
Mechanotransduction
Phase 2 Uterine activation and cervical ripening
Ability of the fetus to provide endocrine signals that initiate parturition has been demonstrated in several species.
Fetal endocrine cascades leading to parturition
Phase 2 Uterine activation and cervical ripening
Synthesized by placenta in relatively large amounts
Maternal plasma CRH levels are low in the 1st T and rise from mend gestation to term
Placental CRH production
Phase 2 Uterine activation and cervical ripening
Only tropic hormone releasing factor to have a specific serum binding protein
CRH
Phase 2 Uterine activation and cervical ripening
Binds most maternal circulating CRH and this inactivated it
CRH binding protein
Phase 2 Uterine activation and cervical ripening
CRH Bp levels in both maternal plasma and amniotic fluid decline, leading to markedly increase level of
Bio available CRH
Phase 2 Uterine activation and cervical ripening
Placental CRH may enhance fetal cortisol production to provide positive feedback so that the placenta produces. Ore CRH
CRH and parturition timing
Phase 2 Uterine activation and cervical ripening
Some have proposed that the rising levels of CRH at the end of gestation reflects
Fetal placental clock
Phase 2 Uterine activation and cervical ripening
Produced by the fetal lung is required for lung maturation
Surfactant protein A
Phase 2 Uterine activation and cervical ripening
Activate fluid macrophage to migrate into the myometrium and induce NF-KB factor that activated inflammatory response
Increased SP-A
Phase 2 Uterine activation and cervical ripening
Diminished estrogen production
Fetal anomalies and delayed parturition
Phase 3 uterine stimulation
Oxytocin and phase 4 parturition
Phase 3 uterine stimulation
Literally, quick birth, first uterotonin to be implicated in parturition initiation
Oxytocin
Phase 3 uterine stimulation
Nano peptide synthesized in the magnocellular neurons of the supraoptic and para ventricular neurons
Oxytocin
Phase 3 uterine stimulation
Pro hormone-> oxytocin during transport
Neurophysin
Phase 3 uterine stimulation
Role of oxytocin in phase 3 and 4
Increase near the end of gestation
Promote prostaglandin release
Synthesized directly in decidual and extra embryonic fetal tissues and in the placenta
Phase 3 uterine stimulation
End of phase 3 of parturition
2nd stage of labor
Phase 3 uterine stimulation
Early past partum period
Early puerperum
Phase 3 uterine stimulation
Phase 4
Oxytocin infusions promotes increased levels of mRNAs from myometrial genes that encode proteins essential for uterine involution
Breast feeding
Prostaglandin and phase 4 of parturition
Levels of prostaglandin or their metabolites in amniotic fluid, maternal plasma, and maternal urine are increased during
Labor
Prostaglandin and phase 4 of parturition
Treatment of pregnant women with prostaglandin by any route causes
Abortion or labor on all gestational ages
Prostaglandin and phase 4 of parturition
Inhibitors to pregnant women will delay spontaneous labor onset and sometimes arrest preterm labor
Administration of prostaglandin H synthase type 2
Prostaglandin and phase 4 of parturition
Prostaglandin synthesis is high and unchanging in the decidua during
Phase 2 and 3 of parturition
Prostaglandin and phase 4 of parturition
Increased in the decidua at term
PGF2
Prostaglandin and phase 4 of parturition
Myometrium synthesis PGHS-2 with labor onset but most prostaglandins likely come from the
Decidua
Prostaglandin and phase 4 of parturition
Also produce prostaglandins
Fetal membrane
Placenta
Prostaglandin and phase 4 of parturition
Further degrade the ECM weakening of fetal membranes
Increase in cytokines
Prostaglandins
Endothelin 1
Is preferentially expressed in smooth muscle and effects an increase in intracellular calcium
Endothelin A receptor
Endothelin 1
Evidence of pathologies and aberrant expression.
Premature birth and uterine leiomyomas
Angiotensin I
There are two G protein linked angiotensin II receptors expressed in the uterus
AT1
AT2
Angiotensin I
Non pregnant
AT2
Angiotensin I
Pregnant
AT1
Angiotensin I
Evokes contraction
Angiotensin II
Maybe another component of the uterotonin system of parturition phase 3
Angiotensin II
Highly resistant to penetration leukocytes, microorganism and neoplastic cells
Amnion
Constitute a selective filter to prevent fetal particulate bound lung and skin secretions from reaching the maternal compartment
Amnion
Amnion
Late pregnancy, amniotic prostaglandin biosynthesis is increased and ________ show increased activity too
A2 and PGH-2
Primary protective and provides immunological acceptance
Relaxation
Also enriched with enzymes that inactivate uterotonin a
Chorion laeve
Generation of decidual uterotonins that act in a paracrine manner on contagious myometrium
Contraction
Decidua
Which of the following is/are not related to uterine contraction?
A. Prostaglandin B. Estrogen C. Oxytocin D. Angiotensin 2 E. Progesterone F. D and E G. NOTA
E. Progesterone
Two general contemporaneous theorems concerning labor initiation
Functional loss of pregnancy maintenance factors
Synthesis of factors that induce parturition