Cross-species withdrawal of MCL1 facilitates postpartum uterine involution in both the mouse and baboon

Chandrashekara Kyathanahalli, Jason Marks, Kennedy Nye, Belinda Lao, Eugene D. Albrecht, Graham W. Aberdeen, Peter W. Nathanielsz, Pancharatnam Jeyasuria, Jennifer C. Condon

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 non-apoptotic 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.

Original languageEnglish (US)
Pages (from-to)4873-4884
Number of pages12
JournalEndocrinology
Volume154
Issue number12
DOIs
StatePublished - Dec 1 2013

ASJC Scopus subject areas

  • Endocrinology

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