Endocrine-Disrupting chemicals (EDCs): evaluation of sex-specific effects on developmental neurotoxicity using microelectrodes array (MEA) recordings

Abstract

Endocrine-disrupting chemicals (EDCs) are known to disturb normal hormone signaling. Disruptors of hormone pathways, such as cypermethrin, permethrin, benzyl butyl phthalate (BBzP) and perfluorooctane sulfonate (PFOS) are associated with human health adverse outcomes, mainly during the neurodevelopmental window. However, there is a knowledge gap that links the neurodevelopmental toxicity of these chemicals and their endocrine disruptor activity. A key aspect of this study is that hormone receptors are differentially expressed between females and males. Thus, the current study aimed to assess the sex-specific effects on the development of neuronal activity of endocrine disrupting chemicals. To do so, rat cortical cells were exposed for 21 days in vitro to different concentrations of EDCs, and the neuronal activity was measured using 48-well microelectrode array (MEA) recordings. Our findings suggest a sex-specific effect after the exposure to PFOS showing an increase of network activity over time only in females. Besides, permethrin presents a decrease in neuronal activity in females and an increase in males. Moreover, results represent a concentration-dependent decrease on neuronal activity after exposure to cypermethrin over time. These findings suggest a relationship between these compounds and the effects on neurodevelopmental effects. Therefore, this research provides a further step to establish scientific evidence on the neuronal toxicity caused by the endocrine disruptor effects. However, more studies are needed to improve the lack of information on the impact of EDCs on neuronal activity and human health.