Department of Obstetrics and Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region of China; Department of Animal Science, Faculty of Animal Science and Export Agriculture, Uva Wellassa University, Badulla, Sri Lanka.
Department of Obstetrics and Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region of China.
Reprod Biol. 2022 Sep;22(3):100666. doi: 10.1016/j.repbio.2022.100666. Epub 2022 Jun 7.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells via receptor angiotensin-converting enzyme 2 (ACE2) and co-receptor transmembrane serine protease 2 (TMPRSS2). However, patients with SARS-CoV-2 infection receiving ACE1 inhibitors had higher ACE2 expression and were prone to poorer prognostic outcomes. Until now, information on the expression of ACE1, ACE2, and TMPRSS2 in human endometrial tissues, and the effects of ACE inhibitors on embryo implantation are limited. We found human endometria expressed ACE1, ACE2, and TMPRSS2 transcripts and proteins. Lower ACE1, but higher ACE2 transcripts were found at the secretory than in the proliferative endometria. ACE1 proteins were weakly expressed in endometrial epithelial and stromal cells, whereas ACE2 and TMPRSS2 proteins were highly expressed in luminal and glandular epithelial cells. However, ACE1 and TMPRSS4 were highly expressed in receptive human endometrial epithelial (Ishikawa and RL95-2) cells, but not in non-receptive AN3CA and HEC1-B cells. Treatment of human endometrial epithelial cells with ACE1 (Captopril, Enalaprilat, and Zofenopril) or ACE2 (DX600) inhibitors did not significantly alter the expression of ACE1, ACE2 and TMPRSS2 transcripts and spheroid (blastocyst surrogate) attachment onto Ishikawa cells in vitro. Taken together, our data suggest that higher ACE2 expression was found in mid-secretory endometrium and the use of ACE inhibitors did not alter endometrial receptivity for embryo implantation.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）通过受体血管紧张素转换酶 2（ACE2）和共受体跨膜丝氨酸蛋白酶 2（TMPRSS2）进入细胞。然而，接受 SARS-CoV-2 感染的患者服用 ACE1 抑制剂后 ACE2 表达更高，预后更差。到目前为止，有关人类子宫内膜组织中 ACE1、ACE2 和 TMPRSS2 的表达以及 ACE 抑制剂对胚胎着床的影响的信息有限。我们发现人类子宫内膜表达 ACE1、ACE2 和 TMPRSS2 转录本和蛋白。与增殖期子宫内膜相比，分泌期子宫内膜中 ACE1 的转录本较低，但 ACE2 的转录本较高。ACE1 蛋白在子宫内膜上皮细胞和基质细胞中表达较弱，而 ACE2 和 TMPRSS2 蛋白在腔上皮细胞和腺上皮细胞中表达较高。然而，在接受性的人子宫内膜上皮（Ishikawa 和 RL95-2）细胞中高度表达 ACE1 和 TMPRSS4，但在非接受性的 AN3CA 和 HEC1-B 细胞中不表达。用 ACE1（卡托普利、依那普利和佐芬普利）或 ACE2（DX600）抑制剂处理人子宫内膜上皮细胞，并未显著改变 ACE1、ACE2 和 TMPRSS2 转录本的表达，也未改变体外胚泡（囊胚替代物）附着在 Ishikawa 细胞上的情况。综上所述，我们的数据表明，中分泌期子宫内膜中 ACE2 表达较高，而 ACE 抑制剂的使用并未改变子宫内膜对胚胎着床的接受能力。
