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

Y Hirota, J Cha, M Yoshie… - Proceedings of the …, 2011 - National Acad Sciences
Y Hirota, J Cha, M Yoshie, T Daikoku, SK Dey
Proceedings of the National Academy of Sciences, 2011National Acad Sciences
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 …
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.
National Acad Sciences