Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Global Transcriptomic Analysis of Placenta From Women With Gestational Sars-Cov-2 Infection During the 3rd Trimester of Pregnancy

Version 1 : Received: 30 May 2023 / Approved: 30 May 2023 / Online: 30 May 2023 (12:36:54 CEST)

How to cite: Tang, Y.; Boggavarapu, N.R.; Aronsson, A.; Gemzell-Danielsson, K.; Lalitkumar, P.G. Global Transcriptomic Analysis of Placenta From Women With Gestational Sars-Cov-2 Infection During the 3rd Trimester of Pregnancy. Preprints 2023, 2023052140. https://doi.org/10.20944/preprints202305.2140.v1 Tang, Y.; Boggavarapu, N.R.; Aronsson, A.; Gemzell-Danielsson, K.; Lalitkumar, P.G. Global Transcriptomic Analysis of Placenta From Women With Gestational Sars-Cov-2 Infection During the 3rd Trimester of Pregnancy. Preprints 2023, 2023052140. https://doi.org/10.20944/preprints202305.2140.v1

Abstract

The COVID-19 pandemic has led to a significant and enduring influence on global health, in-cluding maternal and fetal well-being. Evidence suggests that placental dysfunction is a potential consequence of SARS-CoV-2 infection during pregnancy, which may result in adverse outcomes such as preeclampsia and preterm birth. However, the molecular mechanisms underlying this association remain unclear, and it is uncertain whether a mature placenta can protect the fetus from SARS-CoV-2 infection. To address the above hiatus, we conducted a transcriptome-based study of the placenta in both maternal and fetal compartments. We collected placental samples from 16 women, immediately after term delivery, of which seven had confirmed SARS-CoV-2 in-fection by PCR before parturition. Notably, we did not detect any viral load in either the maternal or fetal compartments of the placenta, regardless of symptomatic status. We extracted total RNA from placental tissues, separately from maternal and fetal compartments, constructed cDNA li-braries, and sequenced them to assess mRNA and small RNA expression. Our analysis revealed 727 differentially expressed genes (DEG) in the maternal placental tissue, with 608 upregulated and 109 downregulated in SARS-CoV-2-positive women compared with healthy, negative wom-en. In contrast, the fetal compartment did not exhibit any significant changes in gene expression with SARS-CoV-2 infection. Specifically, we observed significant downregulation of seven genes belonging to the pregnancy-specific glycoprotein (PSG), related to the immunoglobulin superfam-ily in the maternal compartment with active SARS-CoV-2 infection (fold change range from -13.70 to -5.28, FDR ≤ 0.05). Additionally, comparing symptomatic women with healthy, we identified 14,223 DEGs, with high expression of the inflammatory cytokine IL6 in the maternal placenta of the symptomatic women. Furthermore, KEGG analysis revealed that pathways relat-ed to viral infection, vascular smooth muscle contraction, and oxytocin signaling were altered significantly in symptomatic women. Overall, our study sheds light on the molecular mechanisms underlying the reported clinical risk of preeclampsia and preterm delivery in women with SARS-CoV-2 infection. Nonetheless, studies with larger sample sizes are warranted to further deepen our understanding of the molecular mechanisms of the placenta’s anti-viral effects in ma-ternal SARS-CoV-2 infection.

Keywords

SARS-CoV-2; COVID-19; term pregnancy; vertical transmission; placental gene expression; molecular pathways

Subject

Medicine and Pharmacology, Obstetrics and Gynaecology

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