Phthalates are commonly used in plastic products in daily life. The endocrine-disrupting effects of phthalates have been widely reported. Accumulating evidence from human cohorts and lab animals indicate exposure to phthalates might impair neurodevelopment. However, the direct causal relationship and mechanism between phthalates with neurodevelopment and neurotoxicity have not been firmly established. We found that phthalates (i.e. DBP, DINP, BBP) disrupted the expression of estrogen receptors (esr1, esr2a, esr2b), and impaired neurogenesis in the brain of zebrafish during embryonic development. Moreover, the abnormal expression of estrogen receptors, especially esr2a, was partly rescued in zebrafish which exposed to phthalates, with the estrogen receptor antagonist tamoxifen. Hence, impaired neurogenesis of zebrafish exposed to phthalates was partly reversed by tamoxifen treatment. Moreover, our results show that induced pluripotent stem cells (iPSC)-derived human neurons exposed to phthalates triggered double-strand DNA breaks in vitro. Overall, this study demonstrates that exposure to phthalates affects neurodevelopment in zebrafish embryos and induces neurotoxicity in human neurons partly through disrupting the expression of estrogen receptors.

中文翻译：

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暴露于邻苯二甲酸盐会通过雌激素作用损害神经发育，并在神经元中引起DNA损伤。

邻苯二甲酸酯在日常生活中通常用于塑料产品中。邻苯二甲酸酯的内分泌干扰作用已被广泛报道。来自人类和实验动物的越来越多的证据表明，接触邻苯二甲酸盐可能会损害神经发育。然而，邻苯二甲酸酯与神经发育和神经毒性之间的直接因果关系和机理尚未得到牢固确立。我们发现邻苯二甲酸盐（即DBP，DINP，BBP）破坏了雌激素受体（esr1，esr2a，esr2b）的表达，并损害了斑马鱼大脑在胚胎发育过程中的神经发生。此外，在雌激素受体拮抗剂他莫昔芬的作用下，在暴露于邻苯二甲酸盐的斑马鱼中，部分挽救了雌激素受体，特别是esr2a的异常表达。因此，他莫昔芬治疗可部分逆转斑马鱼暴露于邻苯二甲酸盐的神经发生。此外，我们的结果表明，暴露于邻苯二甲酸盐的诱导多能干细胞（iPSC）衍生的人神经元在体外触发了双链DNA断裂。总体而言，这项研究表明，邻苯二甲酸盐的暴露会影响斑马鱼胚胎中的神经发育，并部分地通过破坏雌激素受体的表达而诱发人神经元的神经毒性。