Endocrine/reproductive disruption by ground and surface waters

一些著名的案例内分泌干扰（艾德）的野生动物种群已被记录。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烃）已被确定为ED的可能原因。然而，对暴露于低水平、环境相关混合物引起的潜在艾德的了解很少。目前的建议是根据本实验室以前对一个哨兵物种-淡水龟-的观察而提出的。在马萨诸塞州军事保留区（MMR）（一个超级基金场地）进行的研究表明，来自一个可能受到污染的地下水羽流影响的试验场地的海龟存在严重的生殖缺陷。与来自对照部位的动物相比，动物成熟缓慢，卵母细胞群减少，精子数量减少，血浆雌二醇降低，卵黄蛋白原水平降低。假设1）生殖缺陷是过去和/或持续暴露于不明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-靶器官轴的一个或多个部位或（B）直接或间接与配子发生过程。具体目标如下：1A。确定肝脏对雌二醇的反应是否受损，1b。测定体内性腺对促性腺激素的反应，1c。测定垂体对不同量促性腺激素释放激素（GnRH）的反应性，2.从参考和受影响部位确定成年、幼年和胚胎海龟中小卵母细胞和精子数量的减少是否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或细胞凋亡率增加所致。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）评估肝脏、性腺和下丘脑对激素刺激反应的体内和体外研究。

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).