Krausz Csilla, Cioppi Francesca
Department of Experimental and Clinical Sciences "Mario Serio", University of Florence, 50139 Florence, Italy.
J Clin Med. 2021 Sep 5;10(17):4009. doi: 10.3390/jcm10174009.
Non-Obstructive Azoospermia (NOA) affects about 1% of men in the general population and is characterized by clinical heterogeneity implying the involvement of several different acquired and genetic factors. NOA men are at higher risk to be carriers of known genetic anomalies such as karyotype abnormalities and Y-chromosome microdeletions in respect to oligo-normozoospermic men. In recent years, a growing number of novel monogenic causes have been identified through Whole Exome Sequencing (WES). Genetic testing is useful for diagnostic and pre-TESE prognostic purposes as well as for its potential relevance for general health. Several epidemiological observations show a link between azoospermia and higher morbidity and mortality rate, suggesting a common etiology for NOA and some chronic diseases, including cancer. Since on average 50% of NOA patients has a positive TESE outcome, the identification of genetic factors in NOA patients has relevance also to the offspring's health. Although still debated, the observed increased risk of certain neurodevelopmental disorders, as well as impaired cardiometabolic and reproductive health profile in children conceived with ICSI from NOA fathers may indicate the involvement of transmissible genetic factors. This review provides an update on the reproductive and general health consequences of known genetic factors causing NOA, including offspring's health.
非梗阻性无精子症（NOA）影响着普通人群中约1%的男性，其特点是临床异质性，这意味着涉及多种不同的后天因素和遗传因素。与少精子症-正常精子症男性相比，NOA男性携带已知遗传异常（如核型异常和Y染色体微缺失）的风险更高。近年来，通过全外显子组测序（WES）已发现越来越多新的单基因病因。基因检测对于诊断和睾丸切开取精术（TESE）前的预后评估很有用，并且因其与总体健康的潜在相关性也很重要。一些流行病学观察表明无精子症与较高的发病率和死亡率之间存在联系，这表明NOA与包括癌症在内的一些慢性疾病有共同的病因。由于平均50%的NOA患者TESE结果呈阳性，因此在NOA患者中识别遗传因素对后代健康也有重要意义。尽管仍存在争议，但观察到的某些神经发育障碍风险增加，以及由NOA父亲通过卵胞浆内单精子注射（ICSI）受孕的儿童心脏代谢和生殖健康受损，可能表明存在可遗传的遗传因素。本综述提供了关于导致NOA的已知遗传因素对生殖和总体健康影响的最新信息，包括对后代健康的影响。
