典型环境污染物对性别决定和性别稳定性的干扰作用机制研究

According to recent research, besides Sry gene on the Y chromosome and Dax1 gene on the X chromosome, some autosomal genes, such as Sox9, Fox12, and Wnt4 etc., could also play important roles in the gonadal differentiation and development as well as the stability of gender. Abnormal expression or mutation of any of these genes could be able to induce gonadal dysgenesis and gender alteration. This was the first study to hypothesize that environmental contaminants might induce gonadal dysgenesis and gender alteration, through the potential interruption in sex determination- and sex stability-related gene expression. This experimental animal-based study aims to 1) reveal the impact of environmental contaminants on the expression of sex determination-related gene(s) in the embryonic gonadal primordial germ cells and alteration in the gonadal histology; 2) find out the impact of environmental contaminants on the expression of sex stability-related gene(s) in the adult mouse testis or ovary and variation in the histology and sex hormone levels; and 3) demonstrate the environmental contaminants interference on sex determination and sex stability and their mechanisms. The expected results from this study would not only reveal the new toxicity of environmental contaminants that is helpful to further explore the action mechanism of environmental hormones and human reproductive disorders, but also provide scientific supports for protecting and improving the human reproductive health and drawing up the prevention strategies.

近年的研究发现，除了Y染色体上的Sry和X染色体上的Dax1基因之外，常染色体上的Sox9、Foxl2和Wnt4等基因，在性腺分化和发育以及性别稳定中起着非常重要的作用，并且其中某一个基因的表达异常或突变，均可以引起性腺发育异常和性别转化。本项目首次提出，环境污染物通过干扰性别决定和性别稳定性相关基因表达，引起性腺分化异常和性别转化的假说。欲通过动物实验，弄清典型环境污染物对胚胎性腺原基细胞中性别决定基因表达以及性腺组织学影响；弄清对成年小鼠睾丸或卵巢中性别稳定性相关基因的表达、组织学改变和性激素水平的影响。阐明环境污染物对性别决定和性别稳定性的干扰作用及其机理。研究结果，不仅首次发现环境污染物的新毒性，有助于进一步深入阐明环境激素的作用机制和人类生殖障碍原因，将为保障和提高人类生殖健康，建立预防对策提供科学依据。