More than 15 million babies are currently born preterm each year. A better mechanistic understanding of prematurity is required for its effective prevention. This study revealed that a mild inflammation induced by LPS absolutely causes preterm birth and neonatal deaths in a genetically-modified mouse model, which naturally exhibits approximately 50% incidence of spontaneous preterm delivery due to cellular senescence and prostaglandin induction in the uterus, and these impairments of parturition are markedly rescued by the combination treatment with an mTOR inhibitor rapamycin and progesterone. Our findings suggest that superimposition of inflammation on genetic predisposition results in high incidence of preterm birth and combined treatment with low doses of rapamycin and progesterone may help reduce the incidence of preterm birth in high-risk women.
JST PRESTO Research Area:
"Elucidation and control of the mechanisms underlying chronic inflammation"
"Molecular aspects of senescence-induced inflammation in mouse models of female reproductive diseases"
Authors: Jeeyeon Cha, Amanda Bartos, Mahiro Egashira, Hirofumi Haraguchi, Tomoko Saito-Fujita, Emma Leishman, Heather Bradshaw, Sudhansu K. Dey, Yasushi Hirota
Title: “Combinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions”
The Journal of Clinical Investigation, Published online 27th, August 2013
Yasushi Hirota, M.D./Ph.D.
Graduate School of Medicine, University of Tokyo
Takafumi Kawaguchi, Fumiharu Kimura,
Life Science Group, Department of Innovation Research, JST