Priority Research Centre for Reproductive Science, Faculty of Science, University of Newcastle, Callaghan, New South Wales, Australia.
Mol Hum Reprod. 2018 Jun 1;24(6):287-298. doi: 10.1093/molehr/gay010.
This article is a personal perspective on male infertility, a condition that is not only extremely prevalent but also a major reason for couples to resort to ART. The introduction of ICSI as a form of facilitated fertilization had a revolutionary impact on our capacity to treat cases of male infertility associated with severely compromised semen quality. However, the widespread use of this technique is also thought to pose risks in terms of the incidence of miscarriage, the health and wellbeing of the offspring and perpetuation of the infertile phenotype into future generations. Furthermore, the advent of ICSI curtailed intellectual interest in the underlying aetiology of male infertility or the development of non-invasive therapeutic strategies that target the male patient rather than the physical deployment of his gametes. As a consequence, progress on elucidating the pathological mechanisms responsible for male infertility has been extremely slow. Genetic and/or epigenetic defects are certainly involved in many cases and may involve mutations/splicing defects affecting the integrity of the testicular RNA profile, as well as the overall kinetics of the transcription process. In addition, spermatogenesis is disrupted by a variety of factors (age, smoking, obesity) many of which are thought to influence fertility and the integrity of sperm DNA through the creation of oxidative stress. Determining the relative contributions of oxidative stress and genetic/epigenetic mutations to the aetiology of male infertility will be a major focus for future research in this important but neglected area.
这是一篇关于男性不育的个人观点，这种情况不仅极其普遍，也是夫妇诉诸于辅助生殖技术（ART）的主要原因。胞浆内单精子注射（ICSI）作为一种辅助受精形式的引入，对我们治疗严重精液质量受损相关的男性不育症的能力产生了革命性的影响。然而，这种技术的广泛应用也被认为存在风险，包括流产的发生率、后代的健康和福祉，以及将不育表型遗传给后代。此外，ICSI 的出现减少了人们对男性不育症基础病因的智力兴趣，也减少了针对男性患者而非其配子物理运用的非侵入性治疗策略的发展。因此，阐明导致男性不育的病理机制的进展非常缓慢。遗传和/或表观遗传缺陷肯定涉及许多情况，并且可能涉及影响睾丸 RNA 谱完整性以及转录过程整体动力学的突变/剪接缺陷。此外，各种因素（年龄、吸烟、肥胖）破坏了精子发生，其中许多因素被认为通过产生氧化应激来影响生育能力和精子 DNA 的完整性。确定氧化应激和遗传/表观遗传突变对男性不育症病因的相对贡献将是未来在这一重要但被忽视的领域的主要研究重点。
