The SARS-CoV-2 receptor, angiotensin-converting enzyme 2, is required for human endometrial stromal cell decidualization†.
The SARS-CoV-2 receptor, angiotensin-converting enzyme 2, is required for human endometrial stromal cell decidualization†.
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DOI：
10.1093/biolre/ioaa211
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发表时间：
2021-02-11
影响因子：
3.6
通讯作者：
Kommagani R
中科院分区：
文献类型：
--
作者：
Chadchan SB;Popli P;Maurya VK;Kommagani R
冠状病毒病2019(新冠肺炎)最早出现在2019年12月，并在全球迅速传播。SARS-CoV-2病毒通过与血管紧张素转换酶2(ACE2)结合进入宿主细胞。尽管大部分关注都集中在呼吸道症状上，但最近的报告表明，SARS-CoV-2会导致早产和流产等妊娠并发症；患有新冠肺炎的女性胎盘曾出现过母体血管灌注不良和蜕膜动脉病。在此，我们报道了ACE2蛋白在月经周期增殖期的子宫内膜上皮细胞和间质细胞中都有表达，在分泌期的间质细胞中的表达增加。原代培养的人子宫内膜间质细胞(HESC)蜕膜化过程中，ACE2的mRNA和蛋白丰度显著增加。此外，转染ACE2靶向siRNA的hESCs的蜕膜化反应减弱，表现为蜕膜化标志物PRL和IGFBP1表达降低，形态缺乏变化。此外，在怀孕期间的小鼠中，ACE2蛋白在子宫上皮细胞中表达，并在怀孕第6天增加基质细胞。黄体酮对小鼠子宫ACE2基因表达的诱导作用强于雌激素组和安慰剂组。这些数据证实了血管紧张素转换酶2在子宫内膜生理学中的作用，提示SARS-CoV-2可能能够进入子宫内膜间质细胞，并引发新冠肺炎患者的病理表现，包括增加早期妊娠丢失的风险。摘要：ACE2蛋白在分泌期人子宫内膜间质细胞中高表达，是子宫内膜间质细胞蜕膜化所必需的。
The coronavirus disease 2019 (COVID-19) first appeared in December 2019 and rapidly spread throughout the world. The SARS-CoV-2 virus enters the host cells by binding to the angiotensin-converting enzyme 2 (ACE2). Although much of the focus is on respiratory symptoms, recent reports suggest that SARS-CoV-2 can cause pregnancy complications such as pre-term birth and miscarriages; and women with COVID-19 have had maternal vascular malperfusion and decidual arteriopathy in their placentas. Here, we report that the ACE2 protein is expressed in both endometrial epithelial and stromal cells in the proliferative phase of the menstrual cycle, and the expression increases in stromal cells in the secretory phase. It was observed that the ACE2 mRNA and protein abundance increased during primary human endometrial stromal cell (HESC) decidualization. Furthermore, HESCs transfected with ACE2-targeting siRNA impaired the full decidualization response, as evidenced by a lack of morphology change and lower expression of the decidualization markers PRL and IGFBP1. Additionally, in mice during pregnancy, the ACE2 protein was expressed in the uterine epithelial cells, and stromal cells increased through day 6 of pregnancy. Finally, progesterone induced Ace2 mRNA expression in mouse uteri more than vehicle or estrogen. These data establish a role for ACE2 in endometrial physiology, suggesting that SARS-CoV-2 may be able to enter endometrial stromal cells and elicit pathological manifestations in women with COVID-19, including an increased risk of early pregnancy loss. Summery Sentence ACE2 protein is highly expressed in human endometrial stromal cells during the secretory phase and is essential for human endometrial stromal cell decidualization.
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影响因子：
3.8
作者：
Brosnihan, K. B.;Bharadwaj, M. S.;Yamaleyeva, L. M.;Neves, L. A. A.
通讯作者：
Neves, L. A. A.
影响因子：
8.3
作者：
Rivière, G;Michaud, A;Vieau, D
通讯作者：
Vieau, D
影响因子：
7.3
作者：
Hamming, I;Timens, W;van Goor, H
通讯作者：
van Goor, H
影响因子：
3.7
作者：
Merrill, DC;Karoly, M;Brosnihan, KB
通讯作者：
Brosnihan, KB
影响因子：
4.5
作者：
Kommagani R;Szwarc MM;Vasquez YM;Peavey MC;Mazur EC;Gibbons WE;Lanz RB;DeMayo FJ;Lydon JP
通讯作者：
Lydon JP