Exploring thyroid development and function: A systems biology search for new chemical disruptor targets

Indiscriminate exposure to chemical substances has emerged as a critical global health concern. Human exposure to emerging contaminants, including pharmaceutical residues, pesticides, food additives, and chemicals employed in packaging and bottle production, is associated with an increased incidence of diseases, including thyroid disorders. Several chemicals potentially dysregulate thyroid embryonic development and the adult hypothalamic‒pituitary‒thyroid (HPT) axis. In this study, we applied systems biology approaches to identify biological processes associated with the most highly upregulated and downregulated genes in human thyroid transcriptome data from both the embryonic and adult stages. As a result, new gene/protein‒chemical interactions linked to recognized toxicities in the thyroid gland and the HPT axis were identified. This analysis identified 195 distinct chemical substances that may interact with these highly expressed proteins and exhibit thyroid toxicity. Our findings underscore the developmental period as a critical window of vulnerability to chemical exposure, with potential adverse effects on thyroid development and programming. Finally, our data suggest new targets for emerging chemicals in the thyroids of adult individuals, potentially compromising thyroid function.