Protein expression of angiotensin-converting enzyme 2, a SARS-CoV-2-specific receptor, in fetal and placental tissues throughout gestation: new insight for perinatal counseling

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 feto-placental 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 38weeks' 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 34weeks. 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 15weeks onwards and in the pediatric controls. It was barely detectable in fetal lung samples at 15 + 5weeks' 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. (C) 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Automated summary

The study found that ACE2 expression can be detected in fetal kidney, rectum, and ileum samples from 15 weeks onward, and was barely detectable in fetal lung samples at 15 + 5 weeks' gestation. ACE2 expression was not found in the fetal brain, heart, or cardiac tissues.