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 language | English (US) |
|---|---|
| Pages (from-to) | E4194-E4203 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 111 |
| Issue number | 40 |
| DOIs | |
| State | Published - Sep 22 2014 |
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Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor. / Gawriluk, Thomas R.; Ko, CheMyong; Hong, Xiaoman; Christenson, Lane K.; Rucker, Edmund B.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 40, 22.09.2014, p. E4194-E4203.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor
AU - Gawriluk, Thomas R.
AU - Ko, CheMyong
AU - Hong, Xiaoman
AU - Christenson, Lane K.
AU - Rucker, Edmund B.
PY - 2014/9/22
Y1 - 2014/9/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84907705896&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84907705896&partnerID=8YFLogxK
U2 - 10.1073/pnas.1409323111
DO - 10.1073/pnas.1409323111
M3 - Article
C2 - 25246579
AN - SCOPUS:84907705896
VL - 111
SP - E4194-E4203
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 40
ER -