Data_Sheet_1_Annexin A7 Regulates Endometrial Receptivity.PDF

A limited window of receptivity is a prerequisite of reproductive success. Indispensable receptivity genes include cyclooxygenase 2 (COX2), an enzyme accomplishing formation of prostaglandin E2 (PGE2). A powerful regulator of PGE2 formation is Annexin A7 (ANXA7). The present study thus explored whether ANXA7 impacts on implantation and fertility. Here we show that ANXA7 is expressed in endometrial tissue and increases upon decidual transformation of human endometrial stromal cells (HESCs) in a time-dependent manner. Silencing ANXA7 significantly decreased the expression of PRL and IGFBP1, canonical decidual marker genes, but enhances COX2 and PGE2 levels. Genetic knockout of AnxA7 in mice significantly increases the number of implantation sites and litter sizes. Further, analysis of human endometrial biopsies showed that ANXA7 transcript and protein levels are decreased during the midluteal window of implantation in women suffering from recurrent pregnancy loss (RPL) when compared to subfertile patients. Taken together, the data indicate that ANXA7 has a conserved role in regulating endometrial receptivity and implantation.

受精成功率之实现，须臾间之接纳窗口为不可或缺之先决条件。其中，不可或缺的接纳相关基因包括环氧化酶2（COX2），该酶负责生成前列腺素E2（PGE2）。前列腺素E2形成之强大调控者，则为Annexin A7（ANXA7）。因此，本研究旨在探究ANXA7是否对着床与生育能力产生影响。本研究结果表明，ANXA7在子宫内膜组织中表达，且随时间推移，在人类子宫内膜基质细胞（HESCs）的蜕膜转化过程中呈现时间依赖性增加。沉默ANXA7显著降低PRL和IGFBP1的表达，这两者均为经典蜕膜标志基因，但同时增强COX2和PGE2的水平。在鼠模型中，AnxA7基因的遗传敲除显著增加了着床位点数量和产仔数。此外，对人类子宫内膜活检的分析显示，与不孕症患者相比，反复妊娠丢失（RPL）患者在植入中期窗口期，ANXA7的转录本和蛋白质水平均降低。综合以上数据，表明ANXA7在调节子宫内膜接纳性和着床过程中的作用具有保守性。