![]() ![]() To study the biology of SARS-CoV-2 in human placenta, we exposed PCS cultures to the virus and collected cell culture media and tissue at selected times p.i. 28, 29 We detected a sharp BCL-2 signal at the surface of the villi with partial overlap with TROP-2, the latter also being detected in the stroma of the villi ( Figure 1C). To further characterize placenta PCS cultures, we used B cell lymphoma 2 (BCL-2) and trophoblast cell-surface antigen 2 (TROP-2), to visualize syncytiotrophoblasts and cytotrophoblasts, respectively. The stereomicroscopic picture in Figure 1B indicates that villous and microstructure in placenta PCSs were preserved following culture over a prolonged period ( Figure 1B). 27 To recapitulate human biology at the maternal-fetal interface, we used an ex vivo model based on organotypic cultures of precision-cut slices (PCSs) of human placenta and evaluated the permissiveness and tropism of third-trimester placenta to SARS-CoV-2.įollowing childbirth, placenta PCSs with a thickness of 500 to 700 μm were prepared and exposed to SARS-CoV-2 or mock treated and analyzed 24–120 h post-infection (p.i.) ( Figure 1A). However, due to the high degree of interspecies placenta diversity, animal models of human placenta diseases are of limited relevance. 22, 23, 24, 25, 26Īssuming the critical nourishing and protecting functions of the placenta, it is crucial to evaluate in further detail the impact of SARS-CoV-2 infection during pregnancy. 20, 21 Severe neonatal COVID-19 is described and sporadic cases of vertical transmission were reported. 14, 16, 17, 18, 19 Moreover, placental infection was reported with the presence of the viral RNA in the umbilical cord, the placental villi, fetal membranes, and trophoblasts, raising concerns that SARS-CoV-2 could affect fetal development. 15 Furthermore, there are indications from several case reports that SARS-CoV-2 infection during pregnancy is associated with placental pathological changes, including placentitis, intervillositis, fibrin deposition, and decidual vascular injury. 5, 12, 13, 14 Large cohort studies have shown that preterm birth, stillbirth, and preeclampsia were significantly increased. 9, 10, 11 Also, up to 40% of SARS-CoV-2 infections during pregnancy are associated with adverse outcomes such as prematurity, miscarriage, preeclampsia, and stillbirth. There is epidemiologic evidence that pregnant women have an elevated risk of developing severe COVID-19 in comparison to age-matched non-pregnant women. 2, 3, 4, 5, 6 Several extrapulmonary complications are described, including acute cardiac and kidney injury, neurological and gastrointestinal manifestations, endothelial damage, and thrombosis in various organs. ![]() Interestingly, the expression of ACE2 and TMPRSS2 are not restricted to the lung tissue but are also expressed in cardiomyocytes, enterocytes, endothelial cells, and placental trophoblasts, indicating that SARS-CoV-2 may have a wide cellular tropism. 1 In addition, SARS-CoV and SARS-CoV-2 both use the endogenous plasma membrane serine protease transmembrane serine protease 2 (TMPRSS2) as a factor for priming and activation. The cell surface receptor for both viruses, the angiotensin-converting enzyme 2 (ACE2), is highly expressed by epithelial cells of the upper and lower respiratory tract. The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), a betacoronavirus with major similarities to SARS-CoV, the causative pathogen of SARS. In conclusion, our data demonstrate the capacity of SARS-CoV-2 to infect and propagate in human placenta and constitute a basis for further investigation of SARS-CoV-2 biology at the maternal-fetal interface. While SARS-CoV-2 infection of placenta PCSs does not cause a detectable cytotoxicity or a pro-inflammatory cytokine response, an upregulation of one order of magnitude of interferon type III transcripts is measured. Viral proteins and/or viral RNA are detected in syncytiotrophoblasts, cytotrophoblasts, villous stroma, and possibly Hofbauer cells. Moreover, the susceptibility of placental tissue to SARS-CoV-2 replication relates to the expression levels of ACE2. Microsynth primer full#Remarkably, exposure of placenta PCSs to SARS-CoV-2 leads to a full replication cycle with infectious virus release. We evaluate SARS-CoV-2 infection at the maternal-fetal interface using precision-cut slices (PCSs) of human placenta. During pregnancy, severe maternal and neonatal outcomes and placental pathological changes have been described. The ongoing SARS-CoV-2 pandemic continues to lead to high morbidity and mortality. ![]()
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