Role of Slit2 upregulation in recurrent miscarriage through regulation of stromal decidualization. (1st January 2021)

• Record Type: Journal Article
• Authors: Chen, Jialing; Liu, Jing; Gao, Shuangquan; Qiu, Yue; Wang, YuJia; Zhang, Yingye; Gao, Lufen; Qi, Guolong; Wu, Yongqi; Lash, Gendie E.; Li, Ping
• Is Part Of: Placenta. Volume 103(2021)
• Page Start: 1
• Page End: 9
• Publication Date: 2021-01-01
• Subjects: Decidualization -- Endometrium -- Human endometrial stromal cell (hESC) -- Decidual stromal cell (DSC) -- Mesenchymal–epithelial transformation (MET) -- Recurrent miscarriage; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2020.10.008
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: Knockout mouse model has shown a relationship between Slit2/Robo1 signalling and altered fertility. Altered expression by endometrial epithelium and trophoblast and is associated with the pathogenesis of pregnancy complications but few studies have investigated the expression of decidual Slit2 in miscarriage. Methods: Expression profiles of Slit2 and Robo1 were measured in human endometrial tissues during the menstrual cycle phases (n = 30), in decidua tissues from recurrent miscarriage (n = 20) and healthy control (n = 20) at 6–8 weeks of gestation. The hormonal regulation of Slit2/Robo1 expression and the role of Slit2/Robo1 signalling in decidualization was investigated in vitro, along with its effects on β-catenin and MET expression. Results: In human endometrium, Slit2 and Robo1 protein expression in stromal cells were decreased between the late-proliferative and early-secretory phase. In recurrent miscarriage patients, decidual expression Slit2 was increased and associated with lower expression of E-cadherin and higher level vimentin compared to controls. In vitro, the expression of Slit2 was downregulated by cAMP and progesterone in hESCs. Upregulation of Slit2 resulted in inhibition of cell decidualization and β-catenin translocation to nucleus. Discussion: This study indicates a functional role for Slit2 in endometrial stromal cell decidualization and the pathogenesis of recurrent miscarriage. Aberrant Increase in Slit2 expression may impairs decidualization of endometrial stromal cells leading to recurrent in recurrent miscarriage. Highlights: Expression of Slit2 in decidua tissues are increased in recurrent miscarriage. Slit2/Robo1 signalling may be associated with the proliferation and differentiation behavior of hESCs. Slit2 inhibits hESCs decidualization via regulating β-catenin and MET transition.