EAPSI: Investigating the effect of environmental contaminants on female reproductive systems in American alligators, an indicator species

越来越多的证据表明，胚胎发育期间暴露于环境污染物可能导致成年生殖功能受损。一个众所周知的例子是，暴露于杀虫剂滴滴涕如何通过蛋壳变薄严重影响许多野生鸟类的繁殖成功。研究表明，出生前接触滴滴涕会改变鸟类雌性生殖道的发育，造成结构变化，从而改变成年后的生殖功能。这项研究将集中在一个重要的哨兵物种，美洲鳄，它拥有一个独特的进化位置，具有类似于其他爬行动物以及鸟类的生殖道的FRT的发展。本研究将探讨是否与雌激素变化相关的途径在鳄鱼FRT的发展中发挥作用。这项研究将在日本冈崎的国家基础生物学研究所进行，与著名的雌激素在女性生殖系统发育和内分泌干扰中的作用专家Taisen Iguchi博士合作。在哺乳动物中，雌性生殖道的区域发育受Hoxa 5'基因时空表达的影响。这些基因在发育中的哺乳动物FRT的区域表达受雌激素调节。由于Hox基因在脊椎动物类群的身体计划规范的高度保守性，本研究假设，Hox基因也参与了发展中的鳄鱼FRT的区域分化，而且，进一步，这些基因是由内源性雌激素调节。Hoxa 5'在胚胎短吻鳄FRT中的表达将通过原位杂交进行定位，雌激素在调节这些基因中的作用将通过比较暴露于外源性雌激素和雌激素受体亚型特异性激动剂的组织中的表达模式来表征。这项研究将提供深入了解健康的生殖系统形成的关键因素，在这个哨兵物种，以及暴露于雌激素环境污染物的潜在破坏性影响。这个NSF EAPSI奖是与日本科学促进协会合作资助的。

There is increasing evidence that exposure to environmental contaminants during embryonic development can lead to impaired adult reproductive function. A well-known example is how exposure to the pesticide DDT severely impacted the reproductive success of many wild birds via eggshell thinning. Studies have shown that exposure to DDT prenatally alters the development of the female reproductive tract (FRT) of birds, causing structural changes that alter adult reproductive function. This study will focus on the development of the FRT in an important sentinel species, the American alligator, which holds a unique evolutionary position with a reproductive tract that bears similarities to other reptiles as well as to birds. This study will investigate whether pathways related to estrogen changes play a role in the development of alligator FRT. This research will be conducted at the National Institute for Basic Biology in Okazaki, Japan, in collaboration with Dr. Taisen Iguchi, a renowned expert on the role of estrogens in female reproductive system development and endocrine disruption. In mammals, regional development of the female reproductive tract is influenced by spatiotemporal expression of Hoxa 5' genes. Regional expression of these genes in the developing mammalian FRT is regulated by estrogens. Due to the highly conserved nature of Hox genes in body plan specification across vertebrate taxa, this study hypothesizes that Hox genes are also involved in regional differentiation of the developing alligator FRT, and, further, that these genes are regulated by endogenous estrogens. Hoxa 5' expression in the embryonic alligator FRT will be localized via in situ hybridization, and the role of estrogens in regulating these genes will be characterized by comparing expression patterns in tissues exposed to exogenous estrogen and estrogen receptor isoform-specific agonists. This study will provide insight into the factors critical for healthy reproductive system formation in this sentinel species, and the potential disruptive impact of exposure to estrogenic environmental contaminants. This NSF EAPSI award is funded in collaboration with the Japan Society for the Promotion of Science.