摘要：一项新的研究报告说，研究人员已经精确地找到了一种基因变异，该变异可帮助解释为什么某些男子会比正常人的生育能力差。 该基因所编码的是一种叫做β-防御素126，该蛋白覆盖在精子的表面并帮助精子穿过女性的子宫颈粘液。 携带这种基因变异株（叫做DEFB126）的男子缺乏β-防御素126，这使得精子游动穿过粘液并最终与卵子结合变得困难得多。 这一DEFB126的遗传变异或许可解释许多无法解释的不育症病例。此外，在男性中进行DEFB126变异株的筛选，可以改进目前的测试，因为目前的测试无法找到近乎五分之一的不孕症夫妇的不孕原因。 Theodore Tollner及其同事对500名新婚的华人夫妇进行了检查并发现，因DEFB126突变而缺乏β-防御素126的男子常常与不育有关（即使是那些没有显示其它与不育有关的缺陷的男子，如精液量不足以及精子活动性低下等）。那些携带β-防御素126变异株的男子的妻子怀孕的可能性比其他夫妇会显著降低，其生孩子的可能性也会减少30%。 一则相关的《观点栏目》对这些发现的临床意义进行了讨论，特别是对携带DEFB126变异株的男子的精子进行处理的可能性做了讨论。（生物探索编辑）
生物探索推荐英文论文摘要：
Sci Transl Med 20 July 2011:
Vol. 3, Issue 92, p. 92ra65
DOI: 10.1126/scitranslmed.3002289
A Common Mutation in the Defensin DEFB126 Causes Impaired Sperm Function and Subfertility
ABSTRACT
A glycosylated polypeptide, β-defensin 126 (DEFB126), derived from the epididymis and adsorbed onto the sperm surface, has been implicated in immunoprotection and efficient movement of sperm in mucosal fluids of the female reproductive tract. Here, we report a sequence variant in DEFB126 that has a two-nucleotide deletion in the open reading frame, which generates an abnormal mRNA. The allele frequency of this variant sequence was high in both a European (0.47) and a Chinese (0.45) population cohort. Binding of the Agaricus bisporus lectin to the sperm surface glycocalyx was significantly lower in men with the homozygous variant (del/del) genotype than in those with either a del/wt or a wt/wt genotype, suggesting an altered sperm glycocalyx with fewer O-linked oligosaccharides in del/del men. Moreover, sperm from del/del carriers exhibited an 84% reduction in the rate of penetration of a hyaluronic acid gel, a surrogate for cervical mucus, compared to the other genotypes. This reduction in sperm performance in hyaluronic acid gels was not a result of decreased progressive motility (average curvilinear velocity) or morphological deficits. Nevertheless, DEFB126 genotype and lectin binding were correlated with sperm performance in the penetration assays. In a prospective cohort study of newly married couples who were trying to conceive by natural means, couples were less likely to become pregnant and took longer to achieve a live birth if the male partner was homozygous for the variant sequence. This common sequence variation in DEFB126, and its apparent effect of impaired reproductive function, will allow a better understanding, clinical evaluation, and possibly treatment of human infertility.
These are normal human sperm. Green dots show the presence of a sugary molecule that allows the sperm to swim through cervical mucus.
