Heightened uterine mammalian target of rapamycin complex 1 (mTORC1) signaling provokes preterm birth in mice
Open accessAbstract
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.
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Rapamycin can prolong the life cycle of many species as diverse as worms and mice, and its signaling system has been implicated as the master regulator of cellular growth and metabolism.
“Rapamycin can also prolong the life cycle of many species as diverse as worms and mice, and its signaling system has been implicated as the master regulator of cellular growth and metabolism.”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [231]
A family of molecules that are the mechanistic target of the rapamycin (mTOR) complex has been attributed a major role in the biology of cell metabolism, growth, longevity, and even preterm birth.
“A family of molecules that are the mechanistic target of the rapamycin (mTOR) complex has been attributed a major role in the biology of cell metabolism, growth, longevity, and even preterm birth(230–236).”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [231]
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- Authors
- Hirota, Y., Cha, J., Yoshie, M., Daikoku, T., & Dey, S. K.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Dey, Sudhansu K.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-10-24
- Volume
- 108
- Issue
- 44
- Pages
- 18073-18078
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3207648
- OpenAlex
- W2107663200
- Cited by
- 125
- References
- 36
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 6 · 2023: 11 · 2022: 6 · 2021: 8 · 2020: 7 · 2019: 8 · 2018: 7 · 2017: 16 · 2016: 9 · 2015: 6 · 2014: 12 · 2013: 10 · 2012: 6
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bill and Melinda Gates Foundation
- Harvard University
- Takeda Science Foundation
- Uehara Memorial Foundation
- National Institutes of Health (HD12304, DA06668)
- University of Illinois at Urbana-Champaign
- Japan Society for the Promotion of Science (23890045)
- National Institute on Aging (F30AG040858)
- National Institute on Drug Abuse (DA06668, R01DA006668, R37DA006668)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32-HD-07463, R37HD012304, T32HD007463, HD-12304)
- Precursory Research for Embryonic Science and Technology
- Topics
- Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- preterm birth, mTORC1 signaling, rapamycin, fetal death, birth timing, decidual cells, mouse model
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Animals, Female, Fetal Death, Immunohistochemistry, Proteins, Uterus, Blotting, Western, Signal Transduction, Tumor Suppressor Protein p53, Multiprotein Complexes, Premature Birth, Cyclin-Dependent Kinase Inhibitor p21, Mice, TOR Serine-Threonine Kinases
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