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

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.

SUBMITTER: Hirota Y

PROVIDER: S-EPMC3207648 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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

Hirota Yasushi Y Cha Jeeyeon J Yoshie Mikihiro M Daikoku Takiko T Dey Sudhansu K SK

Proceedings of the National Academy of Sciences of the United States of America 20111024 44

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 ...[more]

PMID: 22025690

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