title: Progesterone-regulated caspase 3 action in the mouse may play a role in uterine quiescence during pregnancy through fragmentation of uterine myocyte contractile proteins.
abstract: The appropriate timing of the onset of labor is critical to a successful pregnancy, with potentially devastating consequences resulting to both the mother and child with the onset of preterm labor. In this study, we tested the central hypothesis that progesterone maintains uterine quiescence through regulation of active uterine caspase 3. Using the mouse as our model system, we examined, by Western blot analysis, levels of active caspase 3 and its association with the degradation of uterine contractile proteins during pregnancy. Our data demonstrate that caspase 3-specific cleavage fragments of uterine myocyte contractile proteins are elevated in late gestation. Prior to the onset of labor, active caspase 3 levels and fragmentation of the uterine myocyte contractile proteins decline. We postulate that uterine caspase 3 acts as an anticontractile agent maintaining uterine quiescence through degradation of uterine contractile proteins during late pregnancy. We propose that decreased progesterone action during the final days of pregnancy controls the timing of the onset of uterine contractions by removing the anticontractile action of the apoptotic protein caspase 3 locally in the pregnant myometrium.
authors.affiliation: Department of Cell Biology and Physiology, Magee-Women's Research Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Pancharatnam
authors.initials: P
authors.lastname: Jeyasuria
authors.forename: Jaime
authors.initials: J
authors.lastname: Wetzel
authors.forename: Megan
authors.initials: M
authors.lastname: Bradley
authors.forename: Kalpana
authors.initials: K
authors.lastname: Subedi
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Condon
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007745:Labor Onset / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009124:Muscle Proteins / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism* / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014590:Uterine Contraction / Q000378:metabolism; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000199:Actins; D009124:Muscle Proteins; D012333:RNA, Messenger; D011374:Progesterone; C505409:Casp3 protein, mouse; D053148:Caspase 3