Trichloroethylene modifies energy metabolites in the amniotic fluid of Wistar rats

Exposure to trichloroethylene (TCE), an industrial solvent, is associated with several adverse pregnancy outcomes in humans and decreased fetal weight in rats. However, effects of TCE on energy metabolites in amniotic fluid, which have associations with pregnancy outcomes, has not been published previously. In the current exploratory study, timed-pregnant Wistar rats were exposed to 480 mg TCE/kg/day via vanilla wafer or to vehicle (wafer) alone from gestational day (GD) 6-16. Amniotic fluid collected on GD 16 was analyzed for metabolites important in energy metabolism using short chain fatty acid and tricarboxylic acid plus platforms (N = 4 samples/sex/treatment). TCE decreased concentrations of the following metabolites in amniotic fluid for both fetal sexes: 6-phosphogluconate, guanosine diphosphate, adenosine diphosphate, adenosine triphosphate, and flavin adenine dinucleotide. TCE decreased fructose 1,6-bisphosphate and guanosine triphosphate concentrations in amniotic fluid of male but not female fetuses. Moreover, TCE decreased uridine diphosphate-D-glucuronate concentrations, and increased arginine and phosphocreatine concentrations, in amniotic fluid of female fetuses only. No metabolites were increased in amniotic fluid of male fetuses. Pathway analysis suggested that TCE altered folate biosynthesis and pentose phosphate pathway in both sexes. Using metabolite ratios to investigate changes within specific pathways, some ratio alterations, including those in arginine metabolism and phenylalanine metabolism, were detected in females only. Ratio analysis also suggested enzymes, including gluconokinase, as potential TCE targets. Together, results from this exploratory study suggest that TCE differentially modified energy metabolites in amniotic fluid based on sex. These findings may inform future studies of TCE reproductive toxicity.