TDK conference 2025

Nowadays, with packaged products and processed foods being so widely available, the topic of endocrine disruptors is very often discussed in the contexts of the food industry, skincare products and animal health. Environmental exposure to multiple endocrine disruptors is therefore currently a hot-topic in both human- and veterinary medical research that, in certain areas, still remains to be underexplored. In the present in vitro study, our aim is to evaluate whether, and how, combined endocrine disruptor exposure alters the expression of estrogen receptor-β, thyroid hormone receptor-α, and thyroid hormone receptor-β in cerebellar granule neurons. Since both humans and animals are constantly exposed to complex mixtures of known and likely hundreds of unidentified artificial and naturally occuring endocrine disruptors, we aimed to better understand their effects on individual, isolated primary cell cultures, examining a wide range of well-known compounds with such endocrine-disrupting effects.

Our in vitro study demonstrates the impact of exposure to endocrine disruptors on both the mRNA and protein expression of the cell cultures examined. While all four endocrine disruptors (bisphenol-A, zearalenone, camphor and arsenic) visibly altered mRNA expression levels of estrogen receptor-β, thyroid hormone receptor-α, and thyroid hormone receptor-β, their effects on protein expression were markedly less pronounced. This disparity suggests the involvement of post-transcriptional regulatory mechanisms that reduce changes at the translational level.

Contrary to our expectations of additive or synergistic toxicity, co-exposure to multiple endocrine disruptors did not seem to increase receptor expression changes. Instead, certain combinations produced antagonistic or mutually dampening effects, suggesting an “attenuation” phenomenon in which one compound’s activity offset the influence of another. In the present study, we speculate on mechanisms behind this unexpected occurrence, and suggest the potential of arsenic to limit the endocrine disrupting potential of the other three compounds we examined.