内分泌干扰物对动物和人体生殖系统的影响是生态毒理和环境健康研究领域的前沿课题。资料显示环境雌激素可诱导两栖动物发生雌性化性逆转，然而目前对其分子机制的认识还很缺乏。在前期工作基础上我们提出“环境雌激素通过与雌激素受体（ER）结合激活与卵巢发育相关的ER靶基因的转录直接启动卵巢的分化，而跨过由基因型决定的精巢的早期分化过程，最终导致由雄到雌的性逆转”的假设。本项目围绕这一假设，以对环境雌激素高度敏感的非洲爪蟾为模型动物，以环境雌激素炔雌醇为模式化合物，开展环境雌激素诱导两栖动物雌性化分子机制的研究，核心内容是发现参与雌性化过程的若干关键ER靶基因，在此基础上阐明诱导雌性化的分子机制，同时建立基于ER靶基因表达的表征雌性化效应的早期生物标记物方法。本研究可促进环境雌激素对两栖动物生殖内分泌干扰和生态风险的认识，同时也为进一步研究环境雌激素对高等脊椎动物性腺分化发育的影响提供线索。

Effects of endocrine disrupting chemicals on the reproductive systems of animals and humans have received much attention. Data show that environmental estrogens can induce male-to-female sex reversal in amphibians, but the involved molecular mechanisms have been unclear. Based on preliminary work, we proposed that environmental estrogens activate ovarian differentiation by binding ER and activating ER target genes, which strides over testicular differentiation process, resulting in male-to-female reversal. Focusing on this hypothesis, we will use Xenopus laevis as model animal and ethinyloestradiol as model chemical to explore the molecular mechanisms involved in feminization induced by environmental estrogens in amphibians. The core tasks of this project are to find key ER target genes involved in feminization, and then to clarify the molecular mechanisms and establish molecular biomarkers for feminizing effects using sensitive ER target genes. This project will improve the understanding about endoccrine disruption and ecological risk of environmental estrogens on amphibians, and provide a clue for further study on effects of environmental estrogens on gonadal differentiaton and development in higher vertebrates.