Endocrine/reproductive disruption by ground and surface waters

一些众所周知的野生动物种群内分泌干扰（ED）的案例已经被记录在案。在大多数情况下，单一类别的化合物（通常是异种雌激素或芳香烃）已被确定为ED的可能原因。然而，由于暴露于低水平的环境相关混合物而导致的潜在ED的知识很少。目前的建议是根据该实验室以前对一种哨兵物种——淡水龟（Chrysemys picta）的观察而提出的。在马萨诸塞州军事保留区（MMR）进行的一项研究表明，在一个可能受到地下水污染影响的试验场，海龟的繁殖能力明显不足。与对照组动物相比，动物成熟缓慢，卵母细胞群减少，精子数量减少，血浆雌二醇水平降低，卵黄蛋白原水平降低。假设是1)生殖缺陷是过去和/或持续暴露于未识别的内分泌干扰物的结果，2)内分泌干扰物干扰(a)下丘脑-垂体-性腺-靶器官轴在一个或多个位置或(b)直接或间接地干扰配子发生过程。具体目标如下：确定肝生机素对雌二醇的反应是否受损。测定体内对促性腺激素的性腺反应，1c。确定垂体对不同数量的促性腺激素释放激素（GnRH）的反应，2。在成年、幼年和胚胎龟中，根据参考和受影响的部位，确定小卵母细胞和精子数量的减少是由于生殖细胞迁移受损、卵原细胞或精原细胞增殖受损、促性腺激素水平降低还是由于细胞凋亡率提高。体内和体外肝脏、性腺和下丘脑对激素刺激反应的研究将使用各种终点（卵黄蛋白原、类固醇合成和促性腺激素分泌）进行评估。

A number of well-known cases of endocrine disruption (ED) in wildlife populations have been documented. In most instances, a single class of compounds (commonly xenoestrogens or aromatic hydrocarbons) has been identified as the probable cause of the ED. However, knowledge of potential ED caused by exposure to low level, environmentally relevant mixtures is poor. The current proposal is developed from previous observations made by this laboratory on a sentinel species, the freshwater turtle, Chrysemys picta. Studies conducted in the area of the Massachusetts Military Reservation (MMR), a Superfund site, have revealed significant reproductive deficits in turtles from a test site potentially impacted by a contaminated groundwater plumes. Animals are slow to mature, have a reduced oocyte cohort, reduced sperm number, lower plasma estradiol and reduced vitellogenin levels compared to animals from a control site. The hypothesis is 1) that the reproductive deficits are the result of past and/or continuous exposure to unidentified endocrine disruptors, 2) that the endocrine disruptors interfere with (a) the hypothalamic-pituitary-gonadal-target organ axis at one or more sites or (b) directly or indirectly with the process of gametogenesis. The Specific Aims are as follows: 1a. Determine whether the hepatic vitallogenin response to estradiol is impaired, 1b. Determine the gonadal response to gonadotropin in vivo, 1c. Determine pituitary responsiveness to varying amounts of gonadotropin releasing hormone (GnRH), 2. Determine in adult, juvenile and embryonic turtles, from the reference and impacted sites, whether the reduced number of small oocytes and sperm are due to impaired germ cell migration, impaired oogonial or spermatogonial proliferation, reduced gonadotropin levels or to an enhanced rate of apoptosis. In vivo and in vitro studies of liver, gonadal and hypothalamic response to hormone stimuli will be assessed using a variety of endpoints (vitellogenin, steroid synthesis and gonadotropin secretion).