气候变化领域集成服务门户(CCPortal): Decidual cell FKBP51-progesterone receptor binding mediates maternal stress-induced preterm birth

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DOI	10.1073/pnas.2010282118
	Decidual cell FKBP51-progesterone receptor binding mediates maternal stress-induced preterm birth
	Guzeloglu-Kayisli O.; Semerci N.; Guo X.; Larsen K.; Ozmen A.; Arlier S.; Mutluay D.; Nwabuobi C.; Sipe B.; Buhimschi I.; Buhimschi C.; Schatz F.; Kayisli U.A.; Lockwood C.J.
发表日期	2021
ISSN	00278424
卷号	118 期号:11
英文摘要	Depression and posttraumatic stress disorder increase the risk of idiopathic preterm birth (iPTB) however, the exact molecular mechanism is unknown. Depression and stress-related disorders are linked to increased FK506-binding protein 51 (FKBP51) expression levels in the brain and/or FKBP5 gene polymorphisms. Fkbp5- deficient (Fkbp5-/-) mice resist stress-induced depressive and anxiety-like behaviors. FKBP51 binding to progesterone (P4) receptors (PRs) inhibits PR function. Moreover, reduced PR activity and/ or expression stimulates human labor. We report enhanced in situ FKBP51 expression and increased nuclear FKBP51-PR binding in decidual cells of women with iPTB versus gestational age-matched controls. In Fkbp5+/+mice, maternal restraint stress did not accelerate systemic P4 withdrawal but increased Fkbp5, decreased PR, and elevated AKR1C18 expression in uteri at E17.25 followed by reduced P4 levels and increased oxytocin receptor (Oxtr) expression at 18.25 in uteri resulting in PTB. These changes correlate with inhibition of uterine PR function by maternal stress-induced FKBP51. In contrast, Fkbp5-/-mice exhibit prolonged gestation and are completely resistant to maternal stress-induced PTB and labor-inducing uterine changes detected in stressed Fkbp5+/+mice. Collectively, these results uncover a functional P4 withdrawal mechanism mediated by maternal stress-induced enhanced uterine FKBP51 expression and FKPB51- PR binding, resulting in iPTB. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Decidual cells; FKBP51; Maternal stress; Preterm birth; Progesterone receptor
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180265
作者单位	Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, United States; Department of Obstetrics and Gynecology, University of Illinois College of Medicine, Chicago, IL 60612, United States
推荐引用方式 GB/T 7714	Guzeloglu-Kayisli O.,Semerci N.,Guo X.,et al. Decidual cell FKBP51-progesterone receptor binding mediates maternal stress-induced preterm birth[J],2021,118(11).
APA	Guzeloglu-Kayisli O..,Semerci N..,Guo X..,Larsen K..,Ozmen A..,...&Lockwood C.J..(2021).Decidual cell FKBP51-progesterone receptor binding mediates maternal stress-induced preterm birth.Proceedings of the National Academy of Sciences of the United States of America,118(11).
MLA	Guzeloglu-Kayisli O.,et al."Decidual cell FKBP51-progesterone receptor binding mediates maternal stress-induced preterm birth".Proceedings of the National Academy of Sciences of the United States of America 118.11(2021).