Cross-species physiological interactions of endocrine disrupting chemicals with the circadian clock

Endocrine disrupting chemicals (EDCs) are endocrine-active chemical pollutants that disrupt reproductive, neuroendocrine, cardiovascular and metabolic health across species. The circadian clock is a transcriptional oscillator responsible for entraining 24-hour rhythms of physiology, behavior and metabolism. Extensive bidirectional cross talk exists between circadian and endocrine systems and circadian rhythmicity is present at all levels of endocrine control, from synthesis and release of hormones, to sensitivity of target tissues to hormone action. In mammals, a range of hormones directly alter clock gene expression and circadian physiology via nuclear receptor (NR) binding and subsequent genomic action, modulating physiological processes such as nutrient and energy metabolism, stress response, reproductive physiology and circadian behavioral rhythms. The potential for EDCs to perturb circadian clocks or circadian-driven physiology is not well characterized. For this reason, we explore evidence for parallel endocrine and circadian disruption following EDC exposure across species. In the reviewed studies, EDCs dysregulated core clock and circadian rhythm network gene expression in brain and peripheral organs, and altered circadian reproductive, behavioral and metabolic rhythms. Circadian impacts occurred in parallel to endocrine and metabolic alterations such as impaired fertility and dysregulated metabolic and energetic homeostasis. Further research is warranted to understand the nature of interaction between circadian and endocrine systems in mediating physiological effects of EDC exposure at environmental levels.