环境内分泌干扰物对性分化和性发育的神经内分泌调控网络的影响

Effects of environmental endocrine disruptors on neuroendocrine regulatory networks related to sexual differentiation and sexual development:a review of recent studies

环境内分泌干扰物(environmental endocrine disrupters,EEDs)是环境中存在的一大类外源性化合物,可干扰机体神经内分泌系统,影响体内天然激素的合成、释放及与受体结合、代谢等过程,进而导致机体及其子代异常发育。神经内分泌调控网络(尤其是下丘脑调控网络)在机体性分化、性发育中发挥关键作用。神经内分泌系统稳态的失衡可致一系列的异常发育,尤其是处于性发育关键时期的胚胎期与青春期。越来越多的研究表明,大脑是EEDs直接作用位点,神经内分泌调控网络中受EEDs显著干扰的主要有促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)神经元、神经胶质细胞、吻肽/G蛋白偶联受体54(kisspeptin/GPR54)系统及脑内芳香化酶等。此外,EEDs还具有传代效应。笔者就近年来EEDs对性分化和性发育的神经内分泌调控网络影响的研究作一综述。

Environmental endocrine disruptors （EEDs） are pollutants of many exogenous chemical classes, which are ubiquitous and persistent in the environment and can interfere with the neuroendocrine systems,disturb body＇s natural steroidogenesis, secretion, and receptor binding,removal of other aspects, thus lead to abnormal development of the human bodies and their progenies. Neuroendocrine regulatory networks, especially the regulatory networks of the hypothalamus play vital roles in sexual differentiation and the process of puberty. When neuroendocrine homeostasis is disrupted by environmental endocrine chemicals, a variety of perturbations about sexual differentiation and sexual development can ensue,particularly when endocrine disruption occurs during critical developmental periods. Emerging evidences have shown that the brain can he the direct targets of EEDs. Among neuroendocrine regulatory networks, gonadotropin-releasing hormone （GnRH） neurons, the kisspeptin/GPR54 system, glial cells, and brain aromatase are significantly disrupted by EEDs. Besides, EEDs also have trans-generational effects. This article will provide an overview of the effect of environmental endocrine disruption on neuroendocrine regulatory networks related to sexual differentiation and sexual development.