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Impact of endocrine disruptors on androgen and estrogen receptors during intrauterine brain development

Transplacental exposure to endocrine disruptors (EDs) may impair concentration, motor function, and language development, reduce IQ, and possibly induce autism. In addition to epigenetic modifications of DNA and noncoding RNAs, diverse exposure profiles and mixtures of EDs, such as heavy metals, plasticizers, coupled with estrogen receptors (ER) and androgen receptors (AR), may trigger adverse pathways in the developing brain at much lower toxic levels than conventional. Disturbance of estrogen/testosterone balance during early brain development may cause discordance of mitotic dynamic and maturation sequence during neuron migration crucial for building of complex brain architecture. Subplate zone as a major site of synaptogenesis is a transient part of the human brain whose peak of activity is seen at 22-24 gestational weeks (GW). The expression of aromatase in the subplate zone starts around 16th GW but there is no data available on its possible alterations by EDs. As majority of environmental EDs are xenoestrogens it is important to stress that ER-alpha is detected in the human cortex as early as during the 9th GW, with high expression in proliferating zones and cortical plate. In an animal model is has been shown that bisphenol A disturbs levels of ER- alpha, and accelerates neuronal differentiation and migration. Additionally, aromatase inhibitor cotinin increases testosterone levels and disturbs AR levels, which have crucial roles in hippocampal neurogenesis and corpus callosum development. It is hoped that prospective data integration by Systems Biology Graphical Notation using deep learning artificial intelligence could serve for real time investigation of complex EDs effects during intrauterine brain development.

intrauterine brain development ; androgen receptors ; estrogen receptors ; endocrine disruptors ; bisphenol A ; cotinin ; plasticizers ; machine learning ; artificial intelligence

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