Effect of in utero and lactational exposure to a thyroid hormone system disrupting chemical on mouse metabolome and brain transcriptome.

Mice were exposed to a low dose of the model thyroid hormone disruptor, propylthiouracil. Although this had only a modest effect on maternal thyroid hormones production, postnatal analysis of the pups' plasma by mass spectrometry and the brain striatum by RNA sequencing gave evidence of low lasting changes that could reflect an adverse effect on neurodevelopment. Overall, these methods proved to be sensitive enough to detect minor disruptions of thyroid hormone signalling in vivo.

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

Gestating mice were exposed to three chemicals, tetrabromo-bisphenol A (TBBPA; 2mg/kg/day)), amitrole (25 and 50mg/kg/day) and pyraclostrobin (0.4 and 2mg/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 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.