Walters Jessica L H, Gadella Bart M, Sutherland Jessie M, Nixon Brett, Bromfield Elizabeth G
Priority Research Centre for Reproductive Science, Schools of Environmental and Life Sciences and Biomedical Sciences and Pharmacy, Discipline of Biological Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.
Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, The Netherlands.
J Clin Med. 2020 Jan 23;9(2):327. doi: 10.3390/jcm9020327.
Despite the prevalence of male factor infertility, most cases are defined as idiopathic, thus limiting treatment options and driving increased rates of recourse to assisted reproductive technologies (ARTs). Regrettably, our current armory of ARTs does not constitute therapeutic treatments for male infertility, thus highlighting an urgent need for novel intervention strategies. In our attempts to fill this void, we have come to appreciate that the production of pathological levels of oxygen radicals within the male germline are a defining etiology of many idiopathic infertility cases. Indeed, an imbalance of reactive oxygen species can precipitate a cascade of deleterious sequelae, beginning with the peroxidation of membrane lipids and culminating in cellular dysfunction and death. Here, we shine light on the importance of lipid homeostasis, and the impact of lipid stress in the demise of the male germ cell. We also seek to highlight the utility of emerging lipidomic technologies to enhance our understanding of the diverse roles that lipids play in sperm function, and to identify biomarkers capable of tracking infertility in patient cohorts. Such information should improve our fundamental understanding of the mechanistic causes of male infertility and find application in the development of efficacious treatment options.
尽管男性因素导致的不育症很普遍，但大多数病例被定义为特发性的，这限制了治疗选择，并导致求助于辅助生殖技术（ART）的比例增加。遗憾的是，我们目前的ART手段并不构成对男性不育症的治疗方法，因此凸显了对新型干预策略的迫切需求。在我们试图填补这一空白的过程中，我们逐渐认识到男性生殖系中病理性水平的氧自由基产生是许多特发性不育病例的决定性病因。事实上，活性氧的失衡会引发一系列有害后果，从膜脂过氧化开始，最终导致细胞功能障碍和死亡。在此，我们阐明脂质稳态的重要性以及脂质应激对男性生殖细胞死亡的影响。我们还试图强调新兴脂质组学技术的实用性，以增进我们对脂质在精子功能中所起多种作用的理解，并识别能够在患者群体中追踪不育症的生物标志物。这些信息应能改善我们对男性不育症机制原因的基本理解，并在开发有效的治疗方案中得到应用。
