Biomarkers of Neurodevelopmental Effect Can Reduce Uncertainty When Assessing the Risks of Thyroid Disrupting Chemicals
On this page:
Various environmental contaminants can reduce serum thyroid hormones (THs) in laboratory animals and are correlated to thyroid disease in epidemiological studies. As THs control normal brain patterning and function, thyroid disrupting chemicals could also harm neurodevelopment. To address this risk to children’s health, some standardized developmental and reproductive toxicity studies suggest or require serum thyroxine (T4) measures in pregnant, lactating, and developing rats. Any chemical capable of reducing serum T4 in vivo could therefore be considered a thyroid disruptor. However, the developing brain is not often examined concurrently by either histopathology or neurobehavior, making it is unclear when a serum T4 reduction is adverse. To address this data gap, we have worked to understand mechanisms of brain TH action to identify potential biomarkers of neurodevelopmental effect in the rat. In a series of publications, we have shown that abnormal cell migration and brain barrier disruption are two reproducible effects of TH interference in vivo. In these hypothesis-driven investigations, we demonstrated that targeted brain gene expression and histopathology assays, as well as serum microRNAs, could be used in toxicology studies as potential biomarkers of neurodevelopmental effect. Importantly, not only are these biomarkers rooted in the biology of TH action, but they can be assessed in young rats (postnatal day 0 – 14) using relatively rapid and cost effective methodologies. In all, this work suggests that directed evaluation of TH targets in the developing rat brain can strengthen the interpretation of serum T4 measures, thus improving chemical assessment.