Affiliation:
1. Guangzhou Key Laboratory of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University , Guangzhou, China
Abstract
Abstract
Uterine contraction is crucial for a successful labor and the prevention of postpartum hemorrhage. It is enhanced by hypoxia; however, its underlying mechanisms are yet to be elucidated. In this study, transcriptomes revealed that hypoxia-inducible factor-1alpha was upregulated in laboring myometrial biopsies, while blockade of hypoxia-inducible factor-1alpha decreased the contractility of the myometrium and myocytes in vitro via small interfering RNA and the inhibitor, 2-methoxyestradiol. Chromatin immunoprecipitation sequencing revealed that hypoxia-inducible factor-1alpha directly binds to the genome of contraction-associated proteins: the promoter of Gja1 and Ptgs2, and the intron of Oxtr. Silencing the hypoxia-inducible factor-1alpha reduced the expression of Ptgs2, Gja1, and Oxtr. Furthermore, blockade of Gja1 or Ptgs2 led to a significant decrease in myometrial contractions in the hypoxic tissue model, whereas atosiban did not remarkably influence contractility. Our study demonstrates that hypoxia-inducible factor-1alpha is essential for promoting myometrial contractility under hypoxia by directly targeting Gja1 and Ptgs2, but not Oxtr. These findings help us to better understand the regulation of myometrial contractions under hypoxia and provide a promising strategy for labor management and postpartum hemorrhage treatment.
Funder
Department of Science and Technology of Guangdong Province
High-tech Major Featured Technology Program of Guangzhou Municipal Health Commission
Guangzhou Municipal Science and Technology Bureau
National Natural Science Foundation of China
Publisher
Oxford University Press (OUP)
Subject
Cell Biology,General Medicine,Reproductive Medicine
Cited by
5 articles.
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