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Objective: Pregnant women can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet the incidence of perinatal infection is low. We hypothesized that this could be related to low expression of the membrane receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), in the fetoplacental unit. We evaluated protein expression of ACE2 at various gestational ages in both placentae and fetal organs from pregnancies not infected with SARS-CoV-2.Methods: In May 2020, using samples from a registered biobank, we performed immunohistochemical analysis for ACE2 in tissue samples from fetal organs and placentae from five cases of second- or third-trimester medical termination of pregnancy in healthy women (performed between 15 and 38 weeks' gestation), as well as a further two placentae, one from a 7-week spontaneous miscarriage in a non-infected woman and one from a symptomatic pregnant woman positive for SARS-CoV-2 delivered by Cesarean section at 34 weeks. Samples were paraffin-embedded and organ tissues included kidney, brain, lung, intestinal tract, heart and testis. Matching tissues (kidney, intestinal tract, lung and testis) from autopsies of four 8-year-old children were tested as controls. Tissue sections were incubated with rabbit monoclonal anti-ACE2, and protein expression of ACE2 was detected by immunohistochemistry.Results: ACE2 expression was detected in fetal kidney, rectum and ileum samples from 15 weeks onwards and in the pediatric controls. It was barely detectable in fetal lung samples at 15 + 5 weeks' gestation and not detectable thereafter, and, in the pediatric controls, ACE2 was detectable only in type-2 pneumocytes. No ACE2 expression was found in the cerebral ependymal or parenchymal tissues or in cardiac tissues. ACE2 was expressed in placental syncytiotrophoblast and cytotrophoblast samples, but not in the amnion, from 7 weeks onwards. The intensity and distribution of ACE2 staining in the placenta from the symptomatic SARS-CoV-2 woman was similar to that in the non-infected placentae.Conclusions: Marked placental expression of ACE2 provides a rationale for vertical transmission at the cellular level. Absence of ACE2 expression in the fetal brain and heart is reassuring regarding the risk of congenital malformation. Clinical follow-up of infected pregnant women and their children is needed to validate these observations. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]