title: Cross-species withdrawal of MCL1 facilitates postpartum uterine involution in both the mouse and baboon.
abstract: A successful postpartum involution permits the postnatal uterus to rapidly regain its prepregnancy function and size to ultimately facilitate an ensuing blastocyst implantation. This study investigates the molecular mechanisms that govern the initiation of the involution process by examining the signaling events that occur as the uterus transitions from the pregnant to postnatal state. Using mouse and baboon uteri, we found a remarkable cross-species conservation at the signal transduction level as the pregnant uterus initiates and progresses through the involution process. This study originated with the observation of elevated levels of caspase-3 activation in both the laboring mouse and baboon uterus, which we found to be apoptotic in nature as evidenced by the concurrent appearance of cleaved poly(ADP-ribose) polymerase. We previously defined a nonapoptotic and potential tocolytic role for uterine caspase-3 during pregnancy regulated by increased antiapoptotic signaling mediated by myeloid cell leukemia sequence 1 and X-linked inhibitor of apoptosis. In contrast, this study determined that diminished antiapoptotic signaling in the postpartum uterus allowed for both endometrial apoptotic and myometrial autophagic episodes, which we speculate are responsible for the rapid reduction in size of the postpartum uterus. Using our human telomerase immortalized myometrial cell line and the Simian virus-40 immortalized endometrial cell line (12Z), we demonstrated that the withdrawal of antiapoptotic signaling was also an upstream event for both the autophagic and apoptotic processes in the human uterine myocyte and endometrial epithelial cell.
authors.affiliation: PhD, B301, Magee Women's Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213. condonj@pitt.edu.
authors.forename: Chandrashekara
authors.initials: C
authors.lastname: Kyathanahalli
authors.forename: Jason
authors.initials: J
authors.lastname: Marks
authors.forename: Kennedy
authors.initials: K
authors.lastname: Nye
authors.forename: Belinda
authors.initials: B
authors.lastname: Lao
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Albrecht
authors.forename: Graham W
authors.initials: GW
authors.lastname: Aberdeen
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nathanielsz
authors.forename: Pancharatnam
authors.initials: P
authors.lastname: Jeyasuria
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Condon
mesh_terms: D000818:Animals; D001343:Autophagy; D053148:Caspase 3; D002460:Cell Line; D005260:Female; D020287:In Situ Nick-End Labeling; D007743:Labor, Obstetric / Q000502:physiology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism*; D009215:Myometrium / Q000166:cytology; D048530:Papio anubis; D049590:Postpartum Period; D011247:Pregnancy; D015398:Signal Transduction; D015854:Up-Regulation; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D051636:X-Linked Inhibitor of Apoptosis Protein; D053148:Caspase 3