Decreased CD44v3 Expression Impairs Endometrial Stromal Cell Decidualization in Women With Recurrent Implantation Failure
Decreased CD44v3 Expression Impairs Endometrial Stromal Cell Decidualization in Women With Recurrent Implantation Failure
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CD44v3 表达减少会损害反复着床失败女性的子宫内膜基质细胞蜕膜化
DOI：
10.21203/rs.3.rs-1043935/v1
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发表时间：
2021-11
影响因子：
4.4
通讯作者：
Aijun Zhang
中科院分区：
文献类型：
--
作者：
Xiaowei Zhou;Yi Cao;mingjuan Zhou;Mi Han;mengyu Liu;Yanqin Hu;Bufang Xu;Aijun Zhang
复发性着床失败(RIF)患者子宫内膜容受性差的确切发病机制尚不清楚。本研究旨在探讨RIF患者分泌中期子宫内膜不同CD44亚型对子宫内膜容受性的影响。方法采集24例RIF患者和18例输卵管阻塞性不孕症患者(对照组)的分泌期子宫内膜组织标本。用免疫组织化学、定量聚合酶链式反应和免疫印迹法鉴定子宫内膜组织中差异表达的CD44亚型。采用定量聚合酶链式反应(QPCR)和免疫印迹法检测CD44v3过表达和基因敲除对永生化人子宫内膜间质细胞(T-hESCs)和原代hESCs增殖和蜕膜化的影响。结果CD44v3在子宫内膜间质细胞分泌中期的表达明显高于增殖期，而在RIF患者中表达明显降低。CD44v3基因敲除hESCs后，蜕膜化标志物催乳素(PRL)和胰岛素样生长因子结合蛋白-1(IGFBP1)的表达显著降低，而CD44v3过表达后PRL和IGFBP1的表达水平显著升高。此外，CD44v3基因敲除的hESCs在胚胎着床共培养系统中对滋养层细胞生长的支持作用明显不足，而hESCs中CD44v3的过表达促进了滋养层细胞的生长。结论CD44v3基因的低表达抑制了hESCs的增殖和蜕膜化，这可能是RIF患者子宫内膜容受性降低的重要原因。
BackgroundThe precise pathogenesis of poor endometrial receptivity in recurrent implantation failure (RIF) still remains unclear. This study aims to explore 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 two groups of women who had undergone IVF: a) 24 patients with RIF, 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 with immunohistochemistry, qPCR and western blotting. Effects of CD44v3 overexpression and knockdown on proliferation and decidualization of Immortalized human endometrial stromal cells (T-HESCs) and primary HESCs were investigated by qPCR and Western blot. A heterologous co-culture system of embryo implantation was constructed to mimics the process of trophoblast invasion during implantation.ResultsCD44v3 was significantly higher expressed in mid-secretory phase of endometrial stromal cells than proliferation phase, but was notably lower in RIF patients. The expression of decidualization markers, prolactin (PRL) and insulin like growth factor binding protein-1 (IGFBP1), was notably decreased following CD44v3 knockdown, whereas the expression levels of both PRL and IGFBP1 increased after CD44v3 overexpression in HESCs. Furthermore, the CD44v3-knockdown HESCs displayed a significantly deficiency in supporting trophoblast outgrowth through a co-culture system of embryo implantation; however, CD44v3 overexpression in HESCs promoted trophoblast outgrowth.ConclusionThe reduced expression of CD44v3 suppresses HESCs proliferation and decidualization, which might play a pivotal role in poor endometrial receptivity in women with RIF.
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