Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor

Thomas R. Gawriluk, Che Myong Ko, Xiaoman Hong, Lane K. Christenson, Edmund B. Rucker

Research output: Contribution to journalArticle

Abstract

Autophagy is an important cellular process that serves as a companion pathway to the ubiquitin-proteasome system to degrade long-lived proteins and organelles to maintain cell homeostasis. Although initially characterized in yeast, autophagy is being realized as an important regulator of development and disease in mammals. Beclinl (Becn1) is a putative tumor suppressor gene that has been shown to undergo a loss of heterozygosity in 40-75% of human breast, ovarian, and prostate cancers. Because Becnl is a key regulator of autophagy, we sought to investigate its role in female reproduction by using a conditional knockout approach in mice. We find that pregnant females lacking Becn1 in the ovarian granulosa cell population have a defect in progesterone production and a subsequent preterm labor phenotype. Luteal cells in this model exhibit defective autophagy and a failure to accumulate lipid droplets needed for steroidogenesis. Collectively, we show that Becnl provides essential functions in the ovary that are essential for mammalian reproduction.

Original languageEnglish (US)
Pages (from-to)E4194-E4203
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number40
DOIs
StatePublished - Sep 22 2014

ASJC Scopus subject areas

  • General

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