Center for Reproductive Health Sciences, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
Biol Reprod. 2021 Feb 11;104(2):336-343. doi: 10.1093/biolre/ioaa211.
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.
新型冠状病毒病 2019（COVID-19）于 2019 年 12 月首次出现，并迅速在全球范围内传播。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。尽管人们的注意力主要集中在呼吸道症状上，但最近的报道表明，SARS-CoV-2 可导致妊娠并发症，如早产和流产；COVID-19 患者的胎盘出现母体血管功能不全和蜕膜动脉病变。在这里，我们报告 ACE2 蛋白在月经周期增殖期的子宫内膜上皮和基质细胞中表达，在分泌期基质细胞中表达增加。观察到在原代人子宫内膜基质细胞（HESC）蜕膜化过程中 ACE2 mRNA 和蛋白丰度增加。此外，用 ACE2 靶向 siRNA 转染的 HESCs 破坏了完全蜕膜化反应，表现为形态变化缺乏和蜕膜化标志物 PRL 和 IGFBP1 的表达降低。此外，在妊娠小鼠中，ACE2 蛋白在子宫上皮细胞中表达，在妊娠第 6 天，基质细胞增加。最后，孕激素诱导的小鼠子宫中 Ace2 mRNA 表达高于载体或雌激素。这些数据确立了 ACE2 在子宫内膜生理学中的作用，表明 SARS-CoV-2 可能能够进入子宫内膜基质细胞，并在 COVID-19 患者中引起病理表现，包括早期妊娠丢失的风险增加。
