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

Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):18073-8. doi: 10.1073/pnas.1108180108. Epub 2011 Oct 24.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Female
  • Fetal Death
  • Immunohistochemistry
  • Mechanistic Target of Rapamycin Complex 1
  • Mice
  • Multiprotein Complexes
  • Premature Birth*
  • Proteins / metabolism*
  • Signal Transduction*
  • TOR Serine-Threonine Kinases
  • Tumor Suppressor Protein p53 / genetics
  • Uterus / metabolism*

Substances

  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Multiprotein Complexes
  • Proteins
  • Tumor Suppressor Protein p53
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases