Nature Reviews Urology ( IF 12.1 ) Pub Date : 2024-03-25 , DOI: 10.1038/s41585-024-00866-y David F Carrageta 1, 2 , Sara C Pereira 1, 2, 3, 4 , Rita Ferreira 4 , Mariana P Monteiro 1, 2 , Pedro F Oliveira 4 , Marco G Alves 5
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Diets leading to caloric overload are linked to metabolic disorders and reproductive function impairment. Metabolic and hormonal abnormalities stand out as defining features of metabolic disorders, and substantially affect the functionality of the testis. Metabolic disorders induce testicular metabolic dysfunction, chronic inflammation and oxidative stress. The disruption of gastrointestinal, pancreatic, adipose tissue and testicular hormonal regulation induced by metabolic disorders can also contribute to a state of compromised fertility. In this Review, we will delve into the effects of high-fat diets and metabolic disorders on testicular metabolism and spermatogenesis, which are crucial elements for male reproductive function. Moreover, metabolic disorders have been shown to influence the epigenome of male gametes and might have a potential role in transmitting phenotype traits across generations. However, the existing evidence strongly underscores the unmet need to understand the mechanisms responsible for transgenerational paternal inheritance of male reproductive function impairment related to metabolic disorders. This knowledge could be useful for developing targeted interventions to prevent, counteract, and most of all break the perpetuation chain of male reproductive dysfunction associated with metabolic disorders across generations.
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代谢性疾病对精子发生和睾丸代谢的影响
导致热量超载的饮食与代谢紊乱和生殖功能损伤有关。代谢和激素异常是代谢紊乱的典型特征,并极大地影响睾丸的功能。代谢紊乱会导致睾丸代谢功能障碍、慢性炎症和氧化应激。代谢紊乱引起的胃肠道、胰腺、脂肪组织和睾丸激素调节的破坏也可能导致生育能力受损。在这篇综述中,我们将深入研究高脂肪饮食和代谢紊乱对睾丸代谢和精子发生的影响,而睾丸代谢和精子发生是男性生殖功能的关键要素。此外,代谢紊乱已被证明会影响雄性配子的表观基因组,并可能在代际传递表型特征方面发挥潜在作用。然而,现有证据强烈强调,了解与代谢紊乱相关的男性生殖功能损伤的跨代父系遗传机制的需求尚未得到满足。这些知识可能有助于制定有针对性的干预措施,以预防、抵消、最重要的是打破与代际代谢紊乱相关的男性生殖功能障碍的永久链。