Metabolomics Approach to Investigate Estrogen Receptor-Dependent and Independent Effects of o,p′-DDT in the Uterus and Brain of Immature Mice

Previous studies have demonstrated the endocrine disruption of o,p′-DDT. In this study, we used a 1H NMR based metabolomics approach to investigate the estrogenic effects of o,p′-DDT (300 mg/kg) on the uterus and brain after 3 days of oral gavage administration, and ethynylestradiol (EE, 100 μg/kg) was used as a positive control. A supervised statistical analysis (PLS-DA) indicated that o,p′-DDT exerted both estrogenic receptor-(ER)-dependent and independent effects on the uterus but mainly ER-independent effects on the brain at metabolome levels, which was verified by coexposing with the antiestrogenic ICI 182,780. Four changed metabolitesglycine, choline, fumarate, and phenylalaninewere identified as ER-independent alterations in the uterus, while more metabolites, including γ-aminobutyrate, N-acetyl aspartate, and some amino acids, were disturbed based on the ER-independent mechanism in the brain. Together with biological end points, metabolomics is a promising approach to study potential estrogenic chemicals.