精子表观遗传信息对男性不育及胚胎发育具有重要作用。乙肝病毒x蛋白（HBx）广泛参与宿主细胞表观遗传修饰，但其对受精及胚胎发育影响的机制不够明确。申请人前期研究发现，HBV感染者精子组蛋白转换异常且组蛋白甲基转移酶Suv39h1等基因表达下调，印迹基因IGF2、KCNQ1OT1甲基化异常，故我们推测：HBx可参与人精子表观遗传修饰，引起组蛋白异常保留区印迹基因甲基化异常，携带异常印迹基因的精子进而影响胚胎发育。本项目拟探究HBV感染者精液参数与组蛋白异常转换率的相关性，制定HBV感染者组蛋白异常转换率标准；采用免疫共沉淀及鼠精原干细胞质粒转染等技术明确组蛋白异常保留区异常印迹基因形成的机制；在动物水平，过表达/沉默IGF2、KCNQ1OT1探究其对胚胎发育的影响。本研究能从表观遗传角度阐明HBV导致人精子功能及胚胎发育异常的分子机制，为HBV感染者生育力的诊断及治疗措施的研发提供新的理论依据。

The epigenetic information of sperm plays an important role in the male infertility and early development of embryos. Hepatitis B virus X protein (HBx) can be widely involved in the epigenetic modification of the host cell. But the effect mechanism of HBx on hunman sperm function and the development of embryos is still remains unclear.In our pre-experiments, we found that the histone-protamine alternation of HBV infected patients’s sperm is abnomal and the expression of histone methyltransferase Suv39h1 were reduced.Futhermore, the methylation level of promoter area in imprinted gene IGF2、KCNQ1OT1 is abnomal. So we speculate that HBx may be involved in the epigenetic modification of hunman sperm and lead to the abnormality of imprinted gene in the histone retained district. The sperm which carried the abnormal epigenetic information might lead to abnormal embryonic development. The purpose of this project is to analyze the correlation between the semen parameters and the sperm histone-protamine abnormal alternation rate of HBV infected patients, developing the histone-protamine abnormal alternation standard. We will study the mechanism of formation of abnormality of imprinted gene in the histone retained district through co-immunoprecipitation and mass spectrum and plasmid transfection of spermatogonial stem cells arrays.In animal level,we will discuss aberrant imprinted genes on the development of embryos by overexpression or silencing of imprinted gene IGF2、 KCNQ1OT1. This study can elucidate the molecular mechanisms of the effect of HBV on hunman sperm function and embryo development. Aslo,it can provide a new theoretical basis for the diagnosis and develop treatment measures for HBV patients’s fertility.