Term
| Explain why smooth muscle remodeling is so important in the uterus. |
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Definition
During pregnancy, the myometrium must enlarge to encompass an infant and placenta, and then involute and return to its original size.
The myometrium must also balance contractility (menstruation and birth) with quiescence (protection during pregnancy) |
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Term
| Explain the basic structure of the uterus |
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Definition
Unitary smooth muscle (few innervations and large amount of local contacts)
1) Inner layer contains longitudinal fibers
2) Middle layer contains vascular supply in mesh of multi-directional muscle fibers.
3) Outer- longitudinal and circular fibers with nervous innervation in between muscle bundles via varicosities in Schwann cell neuronal coating. |
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Term
| Explain how contractility is regulated in the myometrium during Pregnancy |
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Definition
Pregnant= Stop the contraction by limiting gap junctions and inducing NO!
1) GPCR/cAMP signaling closes gap junctions and progesterone decreases their synthesis (they undergo endocytosis and degradation)
2) Progesterone induces iNOS, which directly inhibits VDCC’s and leads to PKG-activation, which (-) calcium influx, (+) Ca-activated K channels to decrease contractility and (-) sensitivity of calcium-dependent contractile proteins such as calmodulin/MLCK.
Detailed Explanation:
a. Uterine quiescence and low neural conductivity are maintained through GPCR-mediated cAMP signaling, which closes gap junction ion channels.
b. High progesterone levels reduce gap junction protein synthesis (connexin)- reactivation of nuclear connexin synthesis during parturition requires 12-24 hours.
c. Gap junction invagination, endocytosis and degradation are increased.
d. iNOS is induced in smooth muscle cells by progesterone (inhibited by estradiol), where it both directly inhibits voltage-gated calcium channels and binds to GC, increasing cGMP and activating PKG. PKG 1) inhibits calcium influx from ECF and SR, 2) activates Ca-activated K channels to decrease contractility and 3) decrease sensitivity of contractile proteins to calcium. These changes decrease calmodulin/MLCK signaling. |
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Term
| Name 4 types of signaling factors important for pregnancy/parturition in the uterus. |
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Definition
1) Classical Neurotransmitters (NOT REQUIRED for pregnancy)
2) Hormones (oxytocin, estradiol, progesterone)
3) Lipid mediators (prostaglandins, platelet activating
4) Gas (NO) all affect uterine activity. |
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Term
| How is uterine contractility activated in parturition? |
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Definition
| During the last 4-6 weeks, fetal/placental growth > uterine growth, causing uterine tension. This activates stretch-sensitive calcium channels, which causes contraction. |
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Term
| What changes in Neurogenic uterine regulation occur between pregnancy and parturition? |
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Definition
1) Pregnancy (relaxation)- βARs are mostly active. NE…cAMP..cAMP-dependent kinase….calcium-channel and gap junction closure causes relaxation.
2) Parturition (increase contractility)- αARs are mostly active. NE…Receptor-operated channels and IP3 activation….increase in calcium from extracellular environment and SR leading to contraction. |
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Term
| What changes in Hormonal uterine regulation occur between pregnancy and parturition? |
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Definition
1) Pregnancy- Progesterone suppresses gap junctions, increases K permeability (reduces calcium entry), reduced pacemaker activity and increased membrane stability.
2) Parturition- Estrogens increase gap junctions, depolarize sarcolema, increase contractile-factors, induces oxytocin receptors for oxytocin action during labor. |
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