Department of HistologyEmbryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of HistologyEmbryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Reproduction. 2017 Oct;154(4):R123-R131. doi: 10.1530/REP-17-0161. Epub 2017 Jul 26.
Obesity, defined as excessive accumulation of fat in adipose tissue, is a metabolic disorder resulting from behavioral, environmental and heritable causes. Obesity increases the risks of hypertension, diabetes, cardiovascular disease, sleep apnea, respiratory problems, osteoarthritis and cancer. Meanwhile, the negative impact of obesity on male reproduction is gradually recognized. According to the clinical investigations and animal experiments, obesity is correlated with reductions in sperm concentration and motility, increase in sperm DNA damage and changes in reproductive hormones. Several mechanisms can elucidate the effects of obesity on sperm functions and male subfertility, i.e., the excessive conversion of androgens into estrogens in redundant adipose tissue causes sexual hormone imbalance, subsequently resulting in hypogonadism. Secondly, adipokines produced by adipose tissue induce severe inflammation and oxidative stress in male reproductive tract, directly impairing testicular and epididymal tissues. Moreover, increased scrotal adiposity leads to increase gonadal heat, continuously hurting spermatogenesis. Therefore, obesity alters the systematic and regional environment crucial for spermatogenesis in testis and sperm maturation in epididymis, and finally results in poor sperm quality including decreased sperm motility, abnormal sperm morphology and acrosome reaction, changed membrane lipids and increased DNA damage. Furthermore, recent studies indicate that epigenetic changes may be a consequence of increased adiposity. A major effort to identify epigenetic determinants of obesity revealed that sperm DNA methylation and non-coding RNA modification are associated with BMI changes and proposed to inherit metabolic comorbidities across generations. This review will explain how obesity-related changes in males to influence sperm function and male fertility as well.
肥胖是指脂肪在脂肪组织中过度积累，是一种由行为、环境和遗传等多种原因引起的代谢紊乱。肥胖会增加患高血压、糖尿病、心血管疾病、睡眠呼吸暂停、呼吸道问题、骨关节炎和癌症的风险。同时，肥胖对男性生殖的负面影响也逐渐被认识到。根据临床调查和动物实验，肥胖与精子浓度和活力降低、精子 DNA 损伤增加以及生殖激素变化有关。几种机制可以阐明肥胖对精子功能和男性生育能力的影响，即多余脂肪组织中雄激素向雌激素的过度转化导致性激素失衡，进而导致性腺功能减退。其次，脂肪组织产生的脂肪因子会在男性生殖道中引起严重的炎症和氧化应激，直接损害睾丸和附睾组织。此外，阴囊脂肪过多会导致睾丸热量增加，持续损害精子发生。因此，肥胖改变了睾丸中精子发生和附睾中精子成熟所必需的系统性和区域性环境，最终导致精子质量下降，包括精子活力降低、精子形态异常和顶体反应、膜脂改变和 DNA 损伤增加。此外，最近的研究表明，表观遗传变化可能是肥胖的结果。一项识别肥胖相关表观遗传决定因素的重要努力表明，精子 DNA 甲基化和非编码 RNA 修饰与 BMI 变化相关，并提出了通过精子将代谢合并症遗传给后代的可能性。这篇综述将解释肥胖如何改变男性的精子功能和生育能力。
