Chen Zi-Feng, Shen Yi-Feng, Gao Da-Wei, Lin Deng-Feng, Ma Wen-Zhe, Chang De-Gui
State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao, People's Republic of China.
Hospital of Chengdu University of Traditional Chinese Medicine, TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu, People's Republic of China.
Am J Physiol Endocrinol Metab. 2025 Jul 1;329(1):E160-E178. doi: 10.1152/ajpendo.00074.2025. Epub 2025 Jun 16.
Globalization has driven a surge in noncommunicable diseases, including metabolic disorders, which are major global health challenges. These disorders, fueled by high-calorie diets, sedentary lifestyles, and gut microbiota imbalances, disrupt energy metabolism, gastrointestinal function, and vitamin and trace element homeostasis. Sertoli cells provide the metabolic and structural support essential for germ cell development within the seminiferous epithelium. This review examines how metabolic disorders affect male reproductive health, focusing on glucose, lipid, and vitamin metabolism, as well as the gut-testis axis, in relation to Sertoli cell function and the blood-testis barrier (BTB) integrity. Glucose metabolism in Sertoli cells provides lactate to germ cells, which is crucial for spermatogenesis. However, metabolic stressors, such as diabetes, impair glucose transport and lactate production, compromising energy supply. Lipid metabolism, including fatty acid oxidation and lipid droplet dynamics, is essential for energy homeostasis in Sertoli cells. Moreover, the gut microbiota further influences Sertoli cells and BTB integrity via metabolites, such as short-chain fatty acids, which enhance barrier function and reduce inflammation. Conversely, dysbiosis and microbially derived lipopolysaccharides induce oxidative stress and immune responses, leading to BTB disruption and infertility. Deficiencies or imbalances in the levels of these vitamins and trace elements can impair spermatogenesis. This review highlights the complex interplay between metabolic pathways and Sertoli cell function, their collective impact on male fertility, and provides a basis for developing targeted therapeutic strategies, including metabolic modulators, vitamin supplementation, and gut microbiota interventions, to mitigate the effects of metabolic disorders on spermatogenesis and fertility.
全球化推动了包括代谢紊乱在内的非传染性疾病的激增，这些疾病是全球主要的健康挑战。高热量饮食、久坐不动的生活方式和肠道微生物群失衡助长了这些疾病，扰乱了能量代谢、胃肠功能以及维生素和微量元素的稳态。支持细胞为生精上皮内生殖细胞的发育提供必要的代谢和结构支持。本综述探讨了代谢紊乱如何影响男性生殖健康，重点关注与支持细胞功能和血睾屏障（BTB）完整性相关的葡萄糖、脂质和维生素代谢，以及肠-睾轴。支持细胞中的葡萄糖代谢为生殖细胞提供乳酸，这对精子发生至关重要。然而，诸如糖尿病等代谢应激源会损害葡萄糖转运和乳酸生成，从而影响能量供应。脂质代谢，包括脂肪酸氧化和脂滴动态变化，对支持细胞中的能量稳态至关重要。此外，肠道微生物群通过短链脂肪酸等代谢产物进一步影响支持细胞和BTB完整性，短链脂肪酸可增强屏障功能并减轻炎症。相反，微生物群落失调和微生物衍生的脂多糖会诱导氧化应激和免疫反应，导致BTB破坏和不育。这些维生素和微量元素水平的缺乏或失衡会损害精子发生。本综述强调了代谢途径与支持细胞功能之间的复杂相互作用、它们对男性生育能力的综合影响，并为制定有针对性的治疗策略提供了基础，这些策略包括代谢调节剂、维生素补充和肠道微生物群干预，以减轻代谢紊乱对精子发生和生育能力的影响。
