Deciphering a critical role of uterine epithelial SHP2 in parturition initiation at single cell resolution

• Published in: Nature communications Vol. 14; no. 1; pp. 7356 - 14
• Main Authors: Liu, Meng, Ji, Mengjun, Cheng, Jianghong, Li, Yingzhe, Tian, Yingpu, Zhao, Hui, Wang, Yang, Zhu, Sijing, Zhang, Leilei, Xu, Xinmei, Feng, Gen-Sheng, Liang, Xiaohuan, Bao, Haili, Tang, Yedong, Kong, Shuangbo, Lu, Jinhua, Wang, Haibin, Lu, Zhongxian, Deng, Wenbo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.11.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 14; 14/19; 14/32; 38; 49/1; 49/91; 631/250/2504/342; 631/443/494/2732/1577; 64/60; 692/699/2732/1577; Animals; Biochemical Phenomena; Cell proliferation; Communication; Cyclooxygenase-2; Decidua; Enzymes; Epithelium; Female; Fetuses; Humanities and Social Sciences; Humans; Infant, Newborn; Labor, Obstetric; Laboratories; Localization; Macrophages; Mice; Microenvironments; multidisciplinary; Ovaries; Parturition; Pregnancy; Premature Birth; Prostaglandins; Proteins; Science; Science (multidisciplinary); Signal transduction; Stromal cells; Uterus
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-43102-8

The timely onset of female parturition is a critical determinant for pregnancy success. The highly heterogenous maternal decidua has been increasingly recognized as a vital factor in setting the timing of labor. Despite the cell type specific roles in parturition, the role of the uterine epithelium in the decidua remains poorly understood. This study uncovers the critical role of epithelial SHP2 in parturition initiation via COX1 and COX2 derived PGF2α leveraging epithelial specific Shp2 knockout mice, whose disruption contributes to delayed parturition initiation, dystocia and fetal deaths. Additionally, we also show that there are distinct types of epithelium in the decidua approaching parturition at single cell resolution accompanied with profound epithelium reformation via proliferation. Meanwhile, the epithelium maintains the microenvironment by communicating with stromal cells and macrophages. The epithelial microenvironment is maintained by a close interaction among epithelial, stromal and macrophage cells of uterine stromal cells. In brief, this study provides a previously unappreciated role of the epithelium in parturition preparation and sheds lights on the prevention of preterm birth. The mechanism of parturition initiation remains elusive. Here, authors show that epithelium is an underestimated site for parturition initiation via epithelial PGF2a regulated by SHP2-COX1/COX2.