Trichloroethylene and perchloroethylene metabolites have fetal sex-specific RNA expression impacts in a full term placental villous explant model

Exposure to volatile organic chemicals (VOCs) like trichloroethylene (TCE) and perchloroethylene (PCE) has been associated with adverse pregnancy outcomes. We conducted an analysis of gene expression responses to the TCE metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) and the PCE metabolite S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC) in placental explants. Explants from placentas with male and female fetuses were treated with either metabolite at 10 μM or 20 μM (n=4). We measured gene expression using RNA sequencing, conducted differential gene expression analysis, cell type deconvolution and Geneset Enrichment Analysis (GSEA). Gene expression changes were correlated between sexes for DCVC (10 μM: r=0.21; 20 μM: r=0.21) but not for TCVC (10 μM: r=0.02; 20 μM: r=0.01). Despite the small sample size, we observed >100 significant gene expression changes (adjusted p-value < 0.05, absolute log 2 fold-change > 1) and decreased estimated abundance of several immune cells. GSEA showed that downregulated pathways were related to immune processes like phagocytosis and immune tolerance.