title: Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor.
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. Beclin1 (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 Becn1 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 Becn1 provides essential functions in the ovary that are essential for mammalian reproduction.
authors.affiliation: Department of Biology, University of Kentucky, Lexington, KY 40506;
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Gawriluk
authors.affiliation: Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL 61802; and.
authors.forename: CheMyong
authors.initials: C
authors.lastname: Ko
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Hong
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160.
authors.forename: Lane K
authors.initials: LK
authors.lastname: Christenson
authors.affiliation: Department of Biology, University of Kentucky, Lexington, KY 40506; edmund.rucker@uky.edu.
authors.forename: Edmund B
authors.initials: EB
authors.lastname: Rucker
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency* / Q000235:genetics; D001343:Autophagy; D000071186:Beclin-1; D053898:Biosynthetic Pathways / Q000235:genetics; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism / Q000648:ultrastructure; D008184:Luteal Cells / Q000378:metabolism; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D007752:Obstetric Labor, Premature / Q000235:genetics*; D010053:Ovary / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism / Q000648:ultrastructure; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D049452:Green Fluorescent Proteins; D011374:Progesterone