Effects of exposure to the trichloroethylene metabolite S-(1,2-dichlorovinyl)-L-cysteine on HTR-8/SVneo differential gene expression under hypoxic vs. normoxic conditions (O2 < 2%)

Trichloroethylene (TCE) is an industrial solvent and widespread environmental contaminant. Human TCE exposure is prevalent, though epidemiological studies testing TCE exposure and adverse birth outcomes are inconclusive. The TCE metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) exhibits toxicity at human-relevant concentrations in a placental cell line. To date, DCVC cytotoxicity mechanistic studies have only been performed under normoxic conditions. In the current study, two parallel experiments under hypoxic or normoxic conditions were conducted. Genome-wide gene expression and gene set enrichment analyses (GSEA) were used to identify novel genes and pathways altered by human exposure-relevant DCVC concentrations in the human placental cell line HTR-8/SVneo. Differential gene expression in hypoxic vs. normoxic condition and treated vs. control within each condition were explored.