Biological impact of xenobiotics in the female reproductive tract

环境污染物难以生物降解，在食物链中积累，影响各种生物功能。二恶英类化学物质干扰类固醇激素的作用，损害生殖功能。越来越多的证据表明，产前暴露于二恶英类环境化学品会导致暴露母亲的后代甚至后代的长期生殖障碍。这些遗传性生殖功能障碍的分子机制尚未完全了解。拟议的研究将使用独特的细胞模型和转基因小鼠来研究这些化学物质诱导的分子机制。利用女性生殖器官的永生化细胞，我们将研究这些化学物质对上皮细胞功能分化的影响，上皮细胞的功能分化受雌激素和孕激素的影响。我们推测二恶英类化学物质干扰分泌和吸收功能所必需的分子机制。使用二恶英反应的小鼠模型，我们将确定最敏感的时间窗口二恶英暴露在产前和产后的发展。我们将采用现代荧光成像技术和新的高灵敏度的检测和分析技术，以调查染色体外的DNA序列和microRNA模式的改变后，出生前暴露于二恶英。我们的长期目标是确定基因组动力学的机制，这可能会导致遗传性功能性生殖障碍。

Environmental pollutants are resistant to biodegradation, accumulate in the food chain and affect various biological functions. Dioxin-type chemicals interfere with steroid hormone action and impair reproductive functions. There is increasing evidence that prenatal exposure to dioxin-type environmental chemicals results in long-term reproductive disturbances in the offspring of exposed mothers and even in further generations. The molecular mechanisms underlying these heritable reproductive dysfunctions are not fully understood. The proposed research will investigate the molecular mechanisms induced by these chemicals using unique cell models and transgenic mice. Utilizing immortalized cells of female reproductive organs we will study the impact of these chemicals on the functional differentiation of epithelial cells which is regulated under the influence of estrogen and progesterone. We hypothesize that dioxin-type chemicals interfere with molecular mechanisms essential for secretory and resorptive functions. Using dioxin-responsive mouse models we will determine the most sensitive time windows for dioxin exposure during pre- and post-natal development. We will employ modern fluorescence imaging techniques and novel highly sensitive detection and analysis techniques to investigate extra-chromosomal DNA sequences and alterations in microRNA patterns following pre-natal exposure to dioxin. Our long-term goal is to identify the mechanisms of genome dynamics which may confer heritable functional reproductive disorders.