Decreased CD44v3 expression impairs endometrial stromal cell proliferation and decidualization in women with recurrent implantation failure

Reproductive Biology and Endocrinology

Research

Yanqin Hu¹  Yi Cao²  Aijun Zhang³  Mi Han³  Mengyu Liu³  Xiaowei Zhou³  Mingjuan Zhou³  Bufang Xu⁴ 

[1] Department of Histo-Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, 200025, Shanghai, China;Department of Obstetrics and Gynecology, Minhang Hospital, Fudan University, 170 Xin Song Road, 201100, Shanghai, People’s Republic of China;Department of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2Nd Road, 200025, Shanghai, China;Department of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2Nd Road, 200025, Shanghai, China;Department of Histo-Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, 200025, Shanghai, China;

关键词: Recurrent implantation failure;    Endometrial receptivity;    CD44v3;    Proliferation;    Endometrial decidualization;   

DOI  :  10.1186/s12958-022-01042-w

 received in 2021-11-05, accepted in 2022-11-22,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundThe precise pathogenesis of poor endometrial receptivity in recurrent implantation failure (RIF) remains unclear. This study was aimed at exploring the effects of different CD44 isoforms in the mid-secretory phase endometrium on endometrial receptivity in women with RIF.MethodsMid-secretory phase endometrial tissue samples were obtained from the following two groups of women who had undergone IVF: (a) 24 patients with RIF and (b) 18 patients with infertility due to tubal obstruction, who had achieved a successful clinical pregnancy after the first embryo transfer in IVF (control group). Identification of differentially expressed CD44 isoforms in endometrial tissues was assessed using immunohistochemistry, qPCR, and western blotting. Effects of overexpression and knockdown of CD44v3 on proliferation and decidualization of immortalized human endometrial stromal cells (T-HESCs) and primary HESCs were investigated by qPCR and western blot analysis. A heterologous coculture system of embryo implantation was constructed to mimic the process of trophoblast invasion during implantation.ResultsThe expression of CD44v3 was significantly higher in the mid-secretory phase of endometrial stromal cells than in the proliferation phase, but was notably lower in RIF patients. Knockdown of CD44v3 significantly downregulated cell proliferation both in T-HESCs and HESCs. The expression of decidualization markers, prolactin (PRL) and insulin like growth factor binding protein-1 (IGFBP1), was notably decreased following the knockdown of CD44v3, whereas the expression of both PRL and IGFBP1 increased after its overexpression in HESCs. Furthermore, the CD44v3-knockdown HESCs displayed significant deficiency in supporting trophoblast outgrowth in a coculture system of embryo implantation; however, overexpression of CD44v3 in HESCs promoted trophoblast outgrowth.ConclusionThe reduced expression of CD44v3 suppresses the proliferation and decidualization of HESCs, which might play a pivotal role in poor endometrial receptivity in women with RIF.

【 授权许可】

CC BY   
© The Author(s) 2022

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