Epimutations and male infertility

精子发生是有丝分裂和减数分裂、细胞分化和细胞间相互作用的复杂过程，最终导致单倍体精子的形成。DNA甲基化对精子发生的重要性已有报道，表明DNA甲基化的改变可导致生精障碍。特发性男性不育影响大约。30%的不育男性，这表明表观遗传修饰是一个可能的原因。我们将调查错误的甲基化印记(表型突变)是否是男性不育的潜在原因。为此，我们将从生育和不育男性的血液和精液样本中筛选亚硫酸盐处理过的DNA中两个父系印记基因和一个母系印记基因以及一个X染色体和一个生殖细胞特异性基因的甲基化模式。这一结果将澄清表观遗传过程是否对男性不育有实质性影响。此外，这项研究将对男性生殖细胞的上突变有助于通过ART获得的儿童的观察到的效果的假设产生影响。

Spermatogenesis is a complex process of mitotic and meiotic cell divisions, cell differentiation and cell-cell interactions finally leading to the formation of haploid spermatozoa. The importance of DNA methylation for spermatogenesis has been reported, indicating that alterations in DNA methylation could induce spermatogenic impairment. Idiopathic male infertility affects approx. 30% of infertile men, suggesting the involvement of epigenetic modifications as one possible cause. We will investigate whether faulty methylation imprints (epimutations) are a underlying cause of male infertility. For this we will screen the methylation patterns of two paternally and one maternally imprinted gene as well as one X chromosomal and one germ cell-specific gene in bisulphite treated DNA from blood and semen samples of fertile and infertile men. The results will clarify whether epigenetic processes have a substantial impact on male infertility. Moreover, this study will have implications with respect to the hypothesis that epimutations of male germ cells contribute to the observed effects in children obtained by ART.