Project Details
Early Career
Status: Funded - Open
SARS-CoV-2 Infection During Pregnancy: Reprogramming of Lipid Metabolism and impact on Fetal Growth
Summary
BACKGROUND: Maternal COVID-19 infection increases the risk of severe adverse obstetric outcomes that can affect neonatal health, including preterm birth, fetal growth restriction (FGR), and in some cases neurodevelopmental defects in the offspring. Global incidence of FGR is approximately 9.4%, varying by region/country (3.4%-19.3%), with overall adverse outcome estimates ranging from about 5% to 15%. GAP: Studies have shown that SARS-CoV-2 induces dyslipidemia by upregulating lipid metabolism pathways and promoting lipid droplet (LD) accumulation in host cells. There is a lack of research on the impact of SARS-CoV-2 on placental lipid metabolic pathways as an underlying factor associated with the various fetal and neonatal risks that stem from COVID-19 during pregnancy. HYPOTHESIS: SARS-CoV-2 infection during pregnancy reprograms placental lipid metabolism and nutrient transport in trophoblasts via viral protein NSP6, leading to increased inflammation and reduced nutrition available to the developing fetus, resulting in fetal growth restriction. METHODS: This study is designed to compare lipidomic profiles and LD accumulation in placental tissues and cord blood of pregnant women infected with SARS-CoV-2 with healthy pregnancies to determine the impact of SARS-CoV-2 on LD biogenesis pathways. Placental tissue and cord blood samples from pregnant women infected with SARS-CoV-2 and healthy controls for comparison and in vitro studies will utilize cytotrophoblast Jeg-3 cells, primary human trophoblasts, and placental trophoblast organoids. RESULTS: Pending. IMPACT: Our study will identify novel lipid biomarkers associated with SARS-CoV-2 exposed pregnancies and provide insights into the mechanism(s) by which the NSP6 protein may affect lipid dysregulation in trophoblast cells and ultimately contribute to possible FGR. Identification of distinct lipid species associated with SARS-CoV-2 exposure and/or FGR could help clinical management of at-risk pregnancies and improve early pediatric development and health outcomes. Website Link: https://www.bcm.edu/people-search/deepak-kumar-83831