ATF3 deficiency impairs the proliferative-secretory phase transition and decidualization in RIF patients.
ATF3 deficiency impairs the proliferative-secretory phase transition and decidualization in RIF patients.
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ATF3 缺乏会损害 RIF 患者的增殖分泌相变和蜕膜化
DOI：
10.1038/s41419-021-03679-8
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发表时间：
2021-04-12
影响因子：
9
通讯作者：
Yan G
中科院分区：
文献类型：
--
作者：
Wang Z;Liu Y;Liu J;Kong N;Jiang Y;Jiang R;Zhen X;Zhou J;Li C;Sun H;Yan G
蜕膜化是一个复杂的过程，涉及子宫内膜基质的细胞增殖和分化，是建立和支持妊娠所必需的。据报道，蜕膜功能失调是导致复发性植入失败(RIF)的重要原因。在本研究中，我们发现激活转录因子3(ATF3)在RIF患者的子宫内膜中的表达显著下调。ATF3基因在人子宫内膜间质细胞(HESCs)中的敲除阻碍蜕膜的形成，而过表达可触发蜕膜标志物基因的表达，从而改善RIF患者hESCs的蜕膜形成。机制上，ATF3通过抑制miR-135B的表达上调FOXO1，从而促进蜕膜化。此外，RIF患者子宫内膜呈高增殖状态，而ATF3过表达则通过CDKN1A抑制hESCs的增殖。这些数据表明，子宫内膜ATF3在调节蜕膜化和增殖中起着关键作用，子宫内膜ATF3的失调可能是RIF的一个新的原因，因此是RIF的潜在治疗靶点。
Decidualization is a complex process involving cellular proliferation and differentiation of the endometrial stroma and is required to establish and support pregnancy. Dysregulated decidualization has been reported to be a critical cause of recurrent implantation failure (RIF). In this study, we found that Activating transcription factor 3 (ATF3) expression was significantly downregulated in the endometrium of RIF patients. Knockdown of ATF3 in human endometrium stromal cells (hESCs) hampers decidualization, while overexpression could trigger the expression of decidual marker genes, and ameliorate the decidualization of hESCs from RIF patients. Mechanistically, ATF3 promotes decidualization by upregulating FOXO1 via suppressing miR-135b expression. In addition, the endometrium of RIF patients was hyperproliferative, while overexpression of ATF3 inhibited the proliferation of hESCs through CDKN1A. These data demonstrate the critical roles of endometrial ATF3 in regulating decidualization and proliferation, and dysregulation of ATF3 in the endometrium may be a novel cause of RIF and therefore represent a potential therapeutic target for RIF.
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DOI：
10.1186/1477-7827-11-64
发表时间：
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期刊：
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