Combining transcriptomics and metabolomics to assess neurodevelopmental alteration caused by in utero exposure of mice to three putative thyroid hormone system disruptors

Abstract

Gestating mice were exposed to three chemicals, tetrabromo-bisphenol A (TBBPA; 2 mg/kg/day), amitrole (25 and 50 mg/kg/day) and pyraclostrobin (0.4 and 2 mg/kg/day) to assess their capacity to act as thyroid hormone disruptors and compromise neurodevelopment. Propyl-thio-uracyl, a known pharmacological inhibitor of thyroid gland secretion, was used at both high and low dose as a reference thyroid hormone system disruptor (1 ppm, 1500 ppm). A combination of plasma metabolomics and striatum transcriptomics revealed the induced change in pups at the postnatal stages. Although the underlying mechanism is unlikely to involve thyroid hormone disruption, these chemicals had a detectable effect on pups’ neurodevelopment.