Environmental toxicants and reproductive health

描述（申请人提供）：目前，人们对环境污染物通过影响内分泌功能而导致包括人类在内的各种物种生殖和发育异常的可能性表示了相当大的关注和辩论，也越来越清楚的是，由内源激素介导的细胞信号可以被内分泌干扰化合物的存在完全掩盖或触发（EDCs），其充当雌激素模拟物或雌激素拮抗剂。在胎儿发育的关键阶段的这种扰动可能导致发育器官的异常和不可逆的编程，并最终导致成人器官功能障碍或疾病。然而，迄今为止进行的大多数研究未能：1）利用环境相关的低剂量内分泌干扰物和/或适当的控制; 2）将选定的剂量与人体暴露水平联系起来; 3）深入研究胎儿暴露及其对成年生殖能力的影响。本研究的目的是将绵羊胎儿暴露于环境相关的低浓度的常见异种雌激素（双酚和甲氧滴滴涕）在生殖神经内分泌系统分化的关键阶段，并确定这些污染物对生殖周期和模式的卵巢卵泡纵向分布的影响。本研究将利用一种特征良好的动物模型进行生殖研究，明确识别发育关键期，以达到EDC治疗的目标。

DESCRIPTION (provided by applicant): At present, there is considerable concern and debate about the possibility that environmental pollutants, through their effect on endocrine function, are responsible for reproductive and developmental abnormalities in various species including humans, it is also becoming increasingly clear that cellular signals mediated by endogenous hormones can be completely obscured or triggered by the presence of endocrine disrupting compounds (EDCs) which act as estrogen mimics or estrogen antagonists. Such perturbations during critical stages of fetal development can lead to abnormal and irreversible programming of developing organs and finally culminate in adult organ dysfunction or diseases. However, majority of the studies conducted thus far have failed to 1) utilize environmentally relevant low doses of EDCs and/or appropriate controls; 2) relate the selected doses to human exposure levels; and 3) take an indepth took at fetal exposures and its impact on reproductive competence as adult. The goal of this study is to expose sheep fetuses to environmentally relevant low concentrations of common xenoestrogens (bisphenol and methoxychlor) during critical stages of reproductive neuroendocrine system differentiation and to determine the impact of these pollutants on reproductive cyclicity and patterns of ovarian follicular distribution longitudinally. This study will utilize a well-characterized animal model for reproductive research with clearly identified developmental critical periods to target EDC treatment.