二噁英暴露对男性生殖健康的损害及其甲基化作用

Toxicology and epidemiological studies have shown that dioxins (PCDD/Fs) have reproductive toxicity and may cause adverse effect on the male semen quality. And sperm DNA methylation was closely associated with male semen quality. There is a hypothesis that exposure to PCDD/Fs may cause change of sperm DNA methylation to affect male reproductive health. Thus, our study will conduct a nested case-control study to investigate the association between PCDD/Fs exposure and male reproductive health. We will recruit 50 child-bearing age men in case and control group respectively, to analysis the levels of 17 kinds of PCDD/Fs in serum as the exposure biomarkers, to determine the sperm DNA methylation as the epigenetic biomarkers, to detect the semen quality parameters and indices of sperm apoptosis and sperm DNA damage as the effect biomarkers. We will investigate the relevance of PCDD/Fs exposure - sperm DNA methylation level - male reproductive health. Our results would get the PCDD/Fs exposure levels in male population. It may also provide the important basis for the evaluation of exposure to PCDD/Fs and male reproductive health and the effect biomarkers, and would be helpful to fulfill the effects assessment on <Stockholm convention on persistent organic pollutants >by provide basic data.

毒理学和流行病学研究显示，二噁英（PCDD/Fs）具有生殖毒性，损害男性精液质量，且精子DNA甲基化水平与男性精液质量密切相关。基于PCDD/Fs暴露通过影响精子DNA甲基化水平而造成男性生殖健康损害的假设，本项目围绕PCDD/Fs暴露水平与男性生殖损害的关系开展巢式病例对照研究，选择病例组和对照组的育龄期男性各50例，分析研究对象外周血17种PCDD/Fs含量，评估男性人群PCDD/Fs内暴露水平；以精子DNA甲基化作为表观遗传标志物，以精液质量常规参数、精子凋亡、精子DNA损伤为效应指标，探讨PCDD/Fs暴露-精子DNA甲基化水平-男性生殖健康损害的关联性。研究结果将为PCDD/Fs暴露致男性生殖健康损害的风险评估提供基础研究资料和早期生物标志，为我国履行《关于持久性有机污染物的斯德哥尔摩公约》成效评估提供基础数据。

毒理学和流行病学研究显示，二噁英（PCDD/Fs）具有生殖毒性，损害男性精液质量，且精子DNA甲基化水平与男性精液质量密切相关。基于PCDD/Fs暴露通过影响精子DNA甲基化水平而造成男性生殖健康损害的假设，本项目围绕PCDD/Fs暴露水平与男性生殖损害的关系开展研究，检测了育龄期男性外周血中17种PCDD/Fs含量，评估男性人群PCDD/Fs内暴露水平，以精液质量常规参数、精子凋亡、DNA损伤为效应指标，以DNA甲基化作为表观遗传标志物，探讨PCDD/Fs暴露- DNA甲基化水平-男性生殖健康损害的关联性。研究结果发现研究对象血清PCDD/Fs浓度和TEQ-PCDD/Fs处于较低水平，血清中∑PCDFs 和TEQ-∑PCDFs浓度增高与精子总活力降低存在剂量效应关系（p for trend＜0.05；p for trend＜0.01）；血清∑PCDDs和∑PCDD/Fs与彗星长度呈正相关（p for trend＜0.02；p for trend＜0.02）；血清TEQ-∑PCDD、TEQ-∑PCDF增加与死亡细胞率升高呈潜在正相关（p for trend=0.09，p for trend=0.06）。研究结果提示PCDD/Fs环境暴露可能会损害男性生殖健康，引起精液质量下降、精子DNA损伤和细胞凋亡；未发现DNA甲基化在PCDD/Fs环境暴露致精液质量损害中的作用。这些研究结果为PCDD/Fs暴露致男性生殖健康损害的风险评估提供基础研究资料和早期生物标志物，为我国履行《关于持久性有机污染物的斯德哥尔摩公约》成效评估提供基础数据。