Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor.
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Abstract |
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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. |
Year of Publication |
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2014
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Journal |
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Proceedings of the National Academy of Sciences of the United States of America
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Volume |
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111
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Issue |
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40
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Number of Pages |
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E4194-203
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Date Published |
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2014
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ISSN Number |
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0027-8424
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URL |
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https://www.pnas.org/doi/10.1073/pnas.1409323111?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed
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DOI |
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10.1073/pnas.1409323111
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Short Title |
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Proc Natl Acad Sci U S A
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