Ray P F, Toure A, Metzler-Guillemain C, Mitchell M J, Arnoult C, Coutton C
Université Grenoble Alpes, Grenoble, France.
Institut for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Grenoble, France.
Clin Genet. 2017 Feb;91(2):217-232. doi: 10.1111/cge.12905. Epub 2016 Dec 9.
Infertility, defined by the inability of conceiving a child after 1 year is estimated to concern approximately 50 million couples worldwide. As the male gamete is readily accessible and can be studied by a simple spermogram it is easier to subcategorize male than female infertility. Subjects with a specific sperm phenotype are more likely to have a common origin thus facilitating the search for causal factors. Male infertility is believed to be often multifactorial and caused by both genetic and extrinsic factors, but severe cases of male infertility are likely to have a predominant genetic etiology. Patients presenting with a monomorphic teratozoospermia such as globozoospermia or macrospermia with more than 85% of the spermatozoa presenting this specific abnormality have been analyzed permitting to identify several key genes for spermatogenesis such as AURKC and DPY19L2. The study of patients with other specific sperm anomalies such as severe alteration of sperm motility, in particular multiple morphological anomalies of the sperm flagella (MMAF) or sperm unability to fertilize the oocyte (oocyte activation failure syndrome) has also enable the identification of new infertility genes. Here we review the recent works describing the identification and characterization of gene defects having a direct qualitative effect on sperm morphology or function.
不孕症定义为一年后仍无法受孕,据估计全球约有5000万对夫妇受此困扰。由于男性配子易于获取,且可通过简单的精液分析进行研究,因此对男性不孕症进行亚分类比女性不孕症更容易。具有特定精子表型的个体更有可能有共同的病因,从而便于寻找致病因素。男性不育症通常被认为是多因素的,由遗传和外在因素共同导致,但严重的男性不育症可能主要由遗传病因引起。对呈现单形性畸形精子症的患者进行了分析,如圆头精子症或大头精子症,其中超过85%的精子呈现这种特定异常,从而得以鉴定出几个精子发生的关键基因,如AURKC和DPY19L2。对患有其他特定精子异常的患者进行研究,如精子活力严重改变,特别是精子鞭毛多重形态异常(MMAF)或精子无法使卵母细胞受精(卵母细胞激活失败综合征),也能够鉴定出新的不育基因。在此,我们综述了近期有关鉴定和表征对精子形态或功能有直接定性影响的基因缺陷的研究工作。