Skip to main content

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

Author
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.

Year of Publication
:
2014
Journal
:
Proceedings of the National Academy of Sciences of the United States of America
Volume
:
111
Issue
:
40
Number of Pages
:
E4194-203
Date Published
:
2014
ISSN Number
:
0027-8424
URL
:
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
DOI
:
10.1073/pnas.1409323111
Short Title
:
Proc Natl Acad Sci U S A
Download citation