SARS-CoV-2 Entry Factors: ACE2 and TMPRSS2 Are Expressed in Peri-Implantation Embryos and the Maternal-Fetal Interface.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the world, leading to large-scale population infection. Angiotensin-converting enzyme 2 (ACE2) is the receptor of both severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. However, it is still controversial whether vertical transmission exists. In order to investigate the potential risk of SARS-CoV-2 vertical transmission, we explored ACE2 and transmembrane protease serine 2 (TMPRSS2) expression patterns in peri-implantation embryos and the maternal-fetal interface using previously published single-cell transcriptome data. The results show that day 6 (D6) trophectoderm cells (TE) in peri-implantation embryos, as well as syncytiotrophoblast (STB) at 8 weeks of gestation (STB_8W) and extravillous trophoblasts cells (EVT) at 24 weeks of gestation (EVT_24W) in the maternal-fetal interface, strongly co-expressed ACE2 and TMPRSS2, indicating SARS-CoV-2 infection susceptibility. The ACE2 positive-expressing cells in the three cell types mentioned above are found to share common characteristics, which are involved in autophagy and immune-related processes. ACE2 showed no gender bias in post-implantation embryos but showed a significant gender difference in D6_TE, D6 primitive endoderm cells (PE), and ACE2 positive-expressing STBs. These findings indicate that there may be different SARS-CoV-2 infection susceptibilities of D6 embryos of different genders and during the gestation of different genders. Our results reveal potential SARS-CoV-2 infection risks during embryo transfer, peri-implantation embryo development, and gestation.