Open AccessDecidual cell FKBP51–progesterone receptor binding mediates maternal stress–induced preterm birth
Author(s) -
Ozlem GuzelogluKayisli,
Nihan Semerci,
Xin Guo,
Kellie Larsen,
Aslı Özmen,
Sefa Arlıer,
Duygu Mutluay,
Chinedu Nwabuobi,
Bradley Sipe,
Irina A. Buhimschi,
Catalin S. Buhimschi,
Frederick Schatz,
Umit A. Kayisli,
Charles J. Lockwood
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2010282118
Subject(s) - receptor , progesterone receptor , mediator , endocrinology , medicine , biology , cancer , estrogen receptor , breast cancer
Significance Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality. The genetics and molecular characteristics of PTB remain unclear. FKBP51 is an important mediator of the stress response and is implicated in the etiology of stress-related disorders. By combining studies in humans andFkbp5 −/− mice, we show that maternal stress up-regulates FKBP51 levels and enhances binding of FKBP51 to progesterone receptors. FKBP51 binding to progesterone receptors reduces progesterone receptor activity by causing functional progesterone withdrawal that induces PTB. In contrast,Fkbp5 −/− mice are resistant to maternal stress–induced PTB and exhibit prolonged gestation. These findings provide molecular insights into stress-related PTB, indicating the importance of the potential use of inhibitor(s) against FKBP51 to treat PTB in future studies.