不同形状纳米金的雄性生殖系统毒性研究

Recently, with the rapid worsening of environmental pollution, man sperm qualities were decreased and sperm abnormalities were increased, which caused the high incidence of man infertility. New environmental pollutants as nanomaterials may be potentially harmful to reproductive toxicity, causing male infertility. Previous studies indicated nano-sized titanium dioxide (TiO2) administered subcutaneously to pregnant mice, would reduce sperm production of the male offspring mice. Repeated intravenous injections of water-soluble multi-walled carbon nanotubes into male mice can decrease the thickness of the seminiferous epithelium in the testis. Meanwhile, previous studies indicated nanomaterial size, surface area, and shape were the critical factors, which determined the toxicity of nanomaterials. Therefore, we intend to investigate gold nanoparticles, because it is widely used nanomaterials. With the shape feature, we will investigate the enrichment in the testes of different shape gold nanoparticles, such as the spherical, rod, cage, star shape； whether they can penentrate the blood testis barrier (BTB) and the mechanism of them. We will also study male reproductive cells and male reproductive system toxicity of different shape gold nanoparticles in vitro and in vivo. As far as we know, there are no systematic research on male reproductive toxicity of different shape gold nanoparticles. The successful implementation of this project will evaluate the saftey of different shape gold nanoparticles, avoiding to exposure to high dose of toxic gold nanoparticles for reproductive safety. This will be helpful to guide the development of nano industry, synthesis safe and reliable nanomaterials.

近年来随着环境污染的急剧加重，男性精子质量持续下降，精子异常增多，导致男性不育发生率不断增高。新型环境污染物--纳米材料可能存有潜在的生殖毒性，导致男性不育的发生。已有研究证实，孕鼠暴露纳米二氧化钛，将导致子代的睾丸中精子发生异常。雄鼠多次尾静脉注射水溶性的多壁碳纳米管，可导致睾丸的生精管壁变薄。同时，已有研究结果表明尺寸、表面修饰、形状等性质是决定纳米材料毒性的关键因素。因此，本项目拟选一类研究和应用广泛的纳米材料--纳米金为研究对象。围绕形状特征, 研究球形、棒状、笼形、星形等不同形状的纳米金，在睾丸中的富集，能否通过血睾屏障及其机制研究，并评价其对雄性生殖细胞和雄性生殖系统的毒性影响。目前，尚无系统地研究不同形状纳米金的雄性生殖毒性的报道。本项目的顺利实施有助于评价不同形状纳米金的生殖安全性，避免接触毒性较高的纳米金；有利于指导纳米工业的发展，合成出更安全可靠的纳米材料。

申请人按照基金项目任务书进行相关实验研究，取得预期的实验进展。首先利用铜、金为原料合成了五角星状的纳米金星。研究了纳米金星对雄性精原细胞系GC-2和雄性小鼠的生殖毒性。发现聚乙二醇修饰的纳米金星没有明显的雄性生殖毒性。进一步，对幼年雄性大鼠的生殖毒性研究，发现纳米金星进入幼年大鼠睾丸的量会显著增加。最后，我们围绕聚乙二醇修饰的纳米金星对小鼠的成熟精子的影响，研究结果表明聚乙二醇修饰的纳米金星不能进入小鼠的成熟精子，但可以促进小鼠的精子尾部的线粒体空泡化，可能存在一定的雄性生殖毒性风险。综合考虑提示纳米金星毒性较低，可以进入雄性生殖系统，提示纳米金星可成为潜在应用载体，为进一步研究雄性生殖过程调控打下基础。