Whole transcriptome profiling of placental pathobiology in SARS-CoV-2 pregnancies identifies placental dysfunction signatures

Abstract

Pregnant people infected with the SARS-CoV-2 virus have shown a higher incidence of "preeclampsia-like syndrome". Preeclampsia is a systematic syndrome that affects 5% of people worldwide and is the leading cause of maternal mortality. It is characterised by placental dysfunction, leading to poor placental perfusion, maternal hypertension and neurological disturbances. Here, we used whole-transcriptome, spatial profiling of placental tissues to analyse the expression of genes between placentae from pregnant participants who contracted SARS-CoV-2 and those prior to the pandemic. Our analysis of the trophoblast and villous core stromal cell populations revealed tissue-specific pathways enriched in the SARS-CoV-2 placentae that align with a pre-eclampsia signature. Most notably, we found enrichment of pathways involved in vascular tension, blood pressure, inflammation, and oxidative stress. This study illustrates how spatially resolved transcriptomic analysis can aid in understanding the underlying pathogenic mechanisms of SARS-CoV-2 in pregnancy that are thought to induce "preeclampsia-like syndrome". Our study highlights the benefits of spatial profiling to map the crosstalk between trophoblast and villous core stromal cells linked to pathways involved in "preeclampsia-like syndrome."

Implication of viruses in the etiology of preeclampsia

“…96 Notably, this study also identified the upregulation of HSPA1A, an alarmin previously reported to be linked with preeclampsia, 97 in the placenta of SARS-CoV-2-positive women, supporting the mechanistical link between SARS-CoV-2 and preeclampsia. 96 Spatial transcriptomic analysis comparing SARS-CoV-2 infected and non-infected placentas identified the enrichment of signatures associated with hypoxia and placenta dysfunction in SARS-CoV-2 infected placentas, 98 showing the similarity of local changes occurring in preeclampsia and SARS-CoV-2 infection. Using an in vitro STB model induced from trophoblast stem cells, another study demonstrated that SARS-CoV-2 infects the STB via ACE-2, an entry receptor of this virus, 99 leading to cytotoxicity and impaired differentiation of the STB model evaluated by fusion index and human chorionic gonadotropin (hCG) production.…”