AUTHOR=Ouidir Marion , Chatterjee Suvo , Mendola Pauline , Zhang Cuilin , Grantz Katherine. L. , Tekola-Ayele Fasil 

TITLE=Placental Gene Co-expression Network for Maternal Plasma Lipids Revealed Enrichment of Inflammatory Response Pathways

JOURNAL=Frontiers in Genetics

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.681095

DOI=10.3389/fgene.2021.681095

ISSN=1664-8021

ABSTRACT=Maternal dyslipidemia during pregnancy has been associated with suboptimal fetal growth and increased cardiometabolic disease risk in offspring. Altered placental function driven by placental gene expression is a hypothesized mechanism underlying these associations. We tested the relationship between maternal plasma lipid concentrations and placental gene expression. Among 64 pregnant women from the NICHD Fetal Growth Studies – Singleton cohort with maternal first trimester plasma lipids we extracted RNA-Seq on placental samples obtained at birth. Placental gene co-expression networks were validated by regulatory network analysis that integrated transcription factors and gene expression, and genome-wide transcriptome analysis.  Network analysis detected 24 gene co-expression modules in placenta, of which one module was correlated with total cholesterol (r =0.27, P-value =0.03) and LDL-C (r =0.31, P-value =0.01). Genes in the module (n =39 genes) were enriched in inflammatory response pathways. Out of the 39 genes in the module, three known lipid-related genes (MPO, PGLYRP1 and LTF) and MAGEC2 were validated by the regulatory network analysis, and one known lipid-related gene (ALX4) and two germ-cell development-related genes (MAGEC2 and LUZP4) were validated by genome-wide transcriptome analysis. Placental gene expression signatures associated with unfavorable maternal lipid concentrations may be potential pathways underlying later life offspring cardiometabolic traits.