DEFB126是由附睾分泌并包裹到精子表面的一种β防御素，最近文献报道男性DEFB126基因突变率高达20%，纯合子突变精子密度和活力均正常，但穿透宫颈粘液能力降低，导致男性生育力下降。我们新近也发现一个DEFB126基因中新的移码突变，可能导致该蛋白无活性。此外，我们发现DEFB126突变在我国不同地区存在显著差异，变化区间为1.4%-39%。鉴于DEFB126基因突变对男性生育影响显著，我们拟以突变率高的贵州水族育龄男性为研究对象，通过问卷调查和精液检查获得生育信息，荧光定量PCR检查DEFB126基因突变，以多因素统计法获取该人群DEFB126基因突变（特别是新突变）与生育的相关性；自制DEFB126特异性抗体用于抗体封闭实验；通过宫颈粘液穿透试验和凝集素芯片实验等，分析DEFB126基因新突变对精子功能的影响。项目研究所获结果可为辅助生殖临床男性不育病因诊断提供理论依据和方法技术。

A glycosylated polypeptide, β-defensin 126 (DEFB126), derived from the epididymis and adsorbed onto the sperm surface, has been implicated in efficient movement of sperm in mucosal fluids of the female reproductive tract. A recent study shows that ?20% of men carry a dysfunctional polymorphism in the open reading frame of DEFB126 gene. The density and activity of sperms in men with the homozygous variant genotype appear to be normal, but these sperms have a reduced ability to penetrate cervical mucus, and this polymorphism in men is associated with reduced fertility. Our recent study found a novel frame-shift mutation of human DEFB126 gene, which may result in an inactive protein and impair sperm function. In addition, we found that the frequency of DEFB126 mutation is region-dependent in China, varied from 1.4% to 39%. Given the significant impairment of reproductive function by DEFB126 gene mutation, we will further investigate the effect of sequence variation in DEFB126 on reproductivity in a cohort study of the adult males of the Shui Nationality in Guizhou province, who carry high mutation rate of DEFB126 gene. In this research plan, we will analyze the answer sheet of questionnaire survey, genotype allele frequency of DEFB126 gene using real-time PCR from adult males of the Shui Nationality, and use multiple-factor Statistics to analyze the correlation between DEFB126 gene mutation and reproductivity in the population. The results will bring us the relevance of sperm fertility and the mutation of DEFB126 gene, especially for the novel DEFB126 mutant. Moreover, to further study the mutations of DEFB126 on sperm function, we will generate human DEFB126-specific antibody, measure the cervical mucus penetration ability of sperm carrying the novel mutation of DEFB126 gene, test sperm fertility coated by anti-DEFB126 antibody, and identify sarccharide component of DEFB126 using lectin chip assays. The obtained epidemiological data and experimental results of sperm parameters will provide us the relevance of the novel mutation of DEFB126 and sperm infertility, and help us develop a novel diagnostic criteria used in clinical evaluation of Assistant Reproductive Technology.