Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

PNAS 108 (44): 18073-18078

Copyright © 2011 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / MEDICAL SCIENCES

Heightened uterine mammalian target of rapamycin complex 1 (mTORC1) signaling provokes preterm birth in mice

Yasushi Hirotaa,b,c, Jeeyeon Chaa, Mikihiro Yoshiea, Takiko Daikokua, and Sudhansu K. Deya,1

aDivision of Reproductive Sciences, Perinatal Institute, Cincinnati Children's Research Foundation, Cincinnati, OH 45229; bDepartment of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan; and cPrecursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan

Edited by Bert W. O'Malley, Baylor College of Medicine, Houston, TX, and approved September 23, 2011 (received for review May 22, 2011)

Abstract: Although preterm delivery is a major global health issue, its causes and underlying mechanism remain elusive. Using mutant mice, mimicking aspects of human preterm birth, we show here that uterine decidual senescence early in pregnancy via heightened mammalian target of rapamycin complex 1 (mTORC1) signaling is a significant contributor of preterm birth and fetal death, and that these adverse phenotypes are rescued by a low dose of rapamycin, an inhibitor of mTORC1 signaling. This role of mTORC1 signaling in determining the timing of birth in mice may help us better understand the mechanism of the timing of birth in humans and develop new and improved strategies to combat the global problem of preterm birth.

Key Words: uterus • phospho-S6 • p21 • prostaglandins • parturition


Author contributions: Y.H., J.C., T.D., and S.K.D. designed research; Y.H., J.C., M.Y., T.D., and S.K.D. performed research; Y.H., J.C., M.Y., T.D., and S.K.D. analyzed data; and Y.H., J.C., T.D., and S.K.D. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1108180108/-/DCSupplemental.

1To whom correspondence should be addressed. E-mail: sk.dey{at}cchmc.org.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Inhibition of Autophagy by Sera From Pregnant Women.
T. T. Kanninen, B. R. de Andrade Ramos, S. Jaffe, A. M. Bongiovanni, I. M. Linhares, G. C. D. Renzo, and S. S. Witkin (2013)
Reproductive Sciences 20, 1327-1331
   Abstract »    Full Text »    PDF »
Conditional deletion of Tsc1 in the female reproductive tract impedes normal oviductal and uterine function by enhancing mTORC1 signaling in mice.
T. Daikoku, M. Yoshie, H. Xie, X. Sun, J. Cha, L. H. Ellenson, and S. K. Dey (2013)
Mol. Hum. Reprod. 19, 463-472
   Abstract »    Full Text »    PDF »
Contribution of Maternal NODAL to Term Pregnancy.
S. K. Das (2012)
Biol Reprod 86, 193
   Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882