Rosenfeld Cheryl S, Denslow Nancy D, Orlando Edward F, Gutierrez-Villagomez Juan Manuel, Trudeau Vance L
a Department of Biomedical Sciences , University of Missouri , Columbia , MO , USA.
b Thompson Center for Autism and Neurobehavioral Disorders , Columbia , MO , USA.
J Toxicol Environ Health B Crit Rev. 2017;20(5):276-304. doi: 10.1080/10937404.2017.1370083.
In vertebrates, sexual differentiation of the reproductive system and brain is tightly orchestrated by organizational and activational effects of endogenous hormones. In mammals and birds, the organizational period is typified by a surge of sex hormones during differentiation of specific neural circuits; whereas activational effects are dependent upon later increases in these same hormones at sexual maturation. Depending on the reproductive organ or brain region, initial programming events may be modulated by androgens or require conversion of androgens to estrogens. The prevailing notion based upon findings in mammalian models is that male brain is sculpted to undergo masculinization and defeminization. In absence of these responses, the female brain develops. While timing of organizational and activational events vary across taxa, there are shared features. Further, exposure of different animal models to environmental chemicals such as xenoestrogens such as bisphenol A-BPA and ethinylestradiol-EE2, gestagens, and thyroid hormone disruptors, broadly classified as neuroendocrine disrupting chemicals (NED), during these critical periods may result in similar alterations in brain structure, function, and consequently, behaviors. Organizational effects of neuroendocrine systems in mammals and birds appear to be permanent, whereas teleost fish neuroendocrine systems exhibit plasticity. While there are fewer NED studies in amphibians and reptiles, data suggest that NED disrupt normal organizational-activational effects of endogenous hormones, although it remains to be determined if these disturbances are reversible. The aim of this review is to examine how various environmental chemicals may interrupt normal organizational and activational events in poikilothermic vertebrates. By altering such processes, these chemicals may affect reproductive health of an animal and result in compromised populations and ecosystem-level effects.
在脊椎动物中,生殖系统和大脑的性别分化是由内源性激素的组织效应和激活效应精确调控的。在哺乳动物和鸟类中,组织期的典型特征是特定神经回路分化过程中性激素激增;而激活效应则取决于性成熟后期这些相同激素的增加。根据生殖器官或脑区的不同,初始编程事件可能受雄激素调节,或需要将雄激素转化为雌激素。基于哺乳动物模型研究结果的普遍观点是,雄性大脑被塑造为经历雄性化和去雌性化。如果没有这些反应,雌性大脑就会发育。虽然组织事件和激活事件的时间在不同分类群中有所不同,但也有共同特征。此外,在这些关键时期,将不同动物模型暴露于环境化学物质,如双酚A(BPA)和乙炔雌二醇(EE2)等异雌激素、孕激素和甲状腺激素干扰物,这些被广泛归类为神经内分泌干扰化学物质(NED),可能会导致大脑结构、功能以及行为发生类似改变。哺乳动物和鸟类神经内分泌系统的组织效应似乎是永久性的,而硬骨鱼类的神经内分泌系统具有可塑性。虽然两栖动物和爬行动物的NED研究较少,但数据表明NED会扰乱内源性激素正常的组织 - 激活效应,不过这些干扰是否可逆仍有待确定。本综述的目的是研究各种环境化学物质如何干扰变温脊椎动物正常的组织和激活事件。通过改变这些过程,这些化学物质可能会影响动物的生殖健康,并导致种群数量减少和生态系统层面的影响。