多环芳烃环境暴露、精浆miRNA表达与男性精液质量损害的关联研究

Toxicological and epidemiological studies have suggested that exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with decreased semen quality. Recent studies have suggested that miRNA express is closely associated with semen quality. Based on the hypothesis that exposure to PAHs can influence the miRNA express related to spermatogenesis to cause adverse effects on semen quality, the project will explore the associations of environmental exposure to PAHs, seminal plasma miRNA express and semen quality damage, utilizing the data from a large-scale cross-sectional study on exposure to environmental pollutants and male reproductive health conducted in our previous research group. In this project, 12 metabolites of PAHs concentrations in urine will be measured to assess the individual’s exposure levels, 4 candidate miRNA express levels related to spermatogenesis in seminal plasma will be measured as epigenetic biomarkers, and conventional semen quality parameters, sperm apoptosis, and sperm DNA damage will be analyzed as effect biomarkers, and thus to uncover the effect of exposure to PAHs on semen quality damage in agreement of exposures, epigenetics, and effects. The results will provide the basic research data and early biological biomarkers for the risk assessment of human male exposure to PAHs associated with adverse reproductive health outcomes.

毒理学和流行病学研究显示，多环芳烃（PAHs）暴露具有损害男性精液质量的生殖毒性。近年来的研究表明，miRNA表达与男性精液质量密切相关。基于PAHs暴露通过影响精子发生相关miRNA表达而造成男性精液质量损害的假设，本项目依托于课题组已开展的环境污染物暴露与男性生殖健康状况的大样本横断面研究，通过测定研究对象尿样中12种PAHs代谢产物含量评估个体的环境暴露水平，以精浆中4种精子发生相关的候选miRNA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PAHs环境暴露-精浆miRNA表达-男性精液质量损害的关联，在“暴露-表观遗传-效应”一致原则上深入认识PAHs暴露对男性精液质量损害的影响。研究结果将为PAHs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。

毒理学研究显示多环芳烃（PAHs）具有损害男性精液质量的生殖毒性，但流行病学研究结论并不一致。此外，有关PAHs暴露致精液质量损害的作用机制也尚不清楚。本项目通过测定研究对象尿样（n=993）中12种PAHs代谢产物含量评估个体环境暴露水平，以精浆中3种精子发生相关的候选miRNA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，分析了PAHs环境暴露-精浆miRNA表达-男性精液质量损害的关联。.在分析PAHs环境暴露与精液质量常规参数关系时，本项目发现尿1-羟基萘（1-OHNa）与精子总数、精子密度和精子正常形态学百分比降低有关（All P for trends<0.05）；尿总羟基萘（1-OHNa和2-OHNa浓度之和，∑OHNa）与精子密度降低有关（P for trend=0.04）。此外，还发现尿9-羟基菲（9-OHPh）与精液体积和精子直线运动速率降低有关（Both P for trends<0.05）；尿总羟基菲（1-OHPh, 2-OHPh, 3-OHPh, 4-OHPh和 9-OHPh浓度之和，∑OHPh）与精子总数降低有关（P for trend=0.04）。这些剂量-反应关系在限制性立方样条曲线模型中被进一步证实。.在分析PAHs环境暴露与精子凋亡和精子DNA损伤时，本项目发现尿9-羟基芴（9-OHFlu）与精子彗星尾长及精子彗星总长增加有关（P for trend 分别为 0.05 和0.01），尿9-OHPh与正常精子细胞数降低有关（P for trend = 0.04）。这些剂量-反应关系同样在限制性立方样条曲线模型中得到进一步证实。在探讨精子发育相关miRNA在PAHs环境暴露与精液质量关联中的中介作用时，本项目发现精浆miRNA106a在尿9-OHPh与精子密度降低的关联中存在显著的中介效应，中介效应占总效应的43.8%（β= -8.55%; 95%CI：-16.15%，-0.26%）。.本项目研究结果显示环境暴露某些PAHs与男性精液质量降低、精子损伤和精子凋亡有关，精浆miRNA106a可能在菲暴露致精子密度降低中起着介导作用。研究成果相继发表于环境与健康领域顶级期刊《Environ Sci Technol》和《J Hazard Mater》等，为PAHs暴露致男性生殖健康损害的风险评估提供了基础研究资料。