Single‐cell RNA expression profiling of SARS‐CoV‐2‐related ACE2 and TMPRSS2 in human trophectoderm and placenta

Objectives To examine the characteristics and distribution of possible severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) target cells in the human trophectoderm (TE) and placenta. Methods Bioinformatics analysis was performed based on published single‐cell transcriptomic datasets of early TE and first‐ and second‐trimester human placentae. We conducted the transcriptomic analysis of 4198 early TE cells, 1260 first‐trimester placental cells and 189 extravillous trophoblast cells (EVTs) from 24‐week placentae (EVT_24W) using the SMART‐Seq2 method. In addition, to confirm the bioinformatic results, we performed immunohistochemical staining of three first‐trimester, three second‐trimester and three third‐trimester placentae from nine women recruited prospectively to this study. We evaluated the expression of the SARS‐CoV‐2‐related molecules angiotensin‐converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Results Via bioinformatic analysis, we identified the existence of ACE2 and TMPRSS2 expression in human TE as well as in first‐ and second‐trimester placentae. In the human TE, 54.4% of TE1 cells, 9.0% of cytotrophoblasts (CTBs), 3.2% of EVTs and 29.5% of syncytiotrophoblasts (STBs) were ACE2‐positive. In addition, 90.7% of TE1 cells, 31.5% of CTBs, 22.1% of EVTs and 70.8% of STBs were TMPRSS2‐positive. In placental cells, 20.4% of CTBs, 44.1% of STBs, 3.4% of EVTs from 8‐week placentae (EVT_8W) and 63% of EVT_24W were ACE2‐positive, while 1.6% of CTBs, 26.5% of STBs, 1.9% of EVT_8W and 20.1% of EVT_24W were TMPRSS2‐positive. Pathway analysis revealed that EVT_24W cells that were positive for both ACE2 and TMPRSS2 (ACE2 + TMPRSS2‐positive) were associated with morphogenesis of branching structure, extracellular matrix interaction, oxygen binding and antioxidant activity. The ACE2 + TMPRSS2‐positive TE1 cells were correlated with an increased capacity for viral invasion, epithelial‐cell proliferation and cell adhesion. Expression of ACE2 and TMPRSS2 was observed on immunohistochemical staining in first‐, second‐ and third‐trimester placentae. Conclusions ACE2‐ and TMPRSS2‐positive cells are present in the human TE and placenta in all three trimesters of pregnancy, which indicates the possibility that SARS‐CoV‐2 could spread via the placenta and cause intrauterine fetal infection. © 2020 International Society of Ultrasound in Obstetrics and Gynecology