Yue Xiaofeng, Yin Rui, Wu Liling, Li Jinjin, Wang Jianwu, Yan Benhuang, Dai Lingyong, Shen Chongxing, Zhi Yi, Wan Ling, Yang Jigao, Li Weibing
Reproduction. 2025 Feb 7;169(3). doi: 10.1530/REP-24-0242. Print 2025 Mar 1.
Obesity is a prevalent health concern globally, often associated with testicular damage that can lead to male infertility. This study investigates the improvement of obesity-induced testicular damage by ACE2 agonist diminazene aceturate (DIZE) and explores the role of the ACE2/Ang 1-7/MasR axis in this process.
DIZE improved obesity and metabolic disturbances in diet-induced obesity (DIO) mice. An increase in sperm count and motility, along with improved morphology and increased male fertility, was observed after DIZE treatment. Both serum and intratesticular testosterone levels showed an increase. Moreover, ACE2/Ang 1-7/MasR protein levels in the testes were restored, which inhibited germ cells apoptosis, lipid accumulation and oxidative stress, and elevated testosterone synthesis-related proteins. However, the MasR antagonist A779 partially counteracted the improving effects of DIZE on metabolism and the testes of DIO mice. This study shows that DIZE treatment has protective effects against obesity-induced testicular injury by activating the ACE2/Ang 1-7/MasR axis.
肥胖是全球普遍关注的健康问题,常与可导致男性不育的睾丸损伤相关。本研究调查了血管紧张素转换酶2(ACE2)激动剂乙酰马嗪(DIZE)对肥胖诱导的睾丸损伤的改善作用,并探讨了ACE2/血管紧张素1-7/ Mas受体(MasR)轴在此过程中的作用。
DIZE改善了饮食诱导肥胖(DIO)小鼠的肥胖和代谢紊乱。DIZE治疗后观察到精子数量和活力增加,形态改善,雄性生育力提高。血清和睾丸内睾酮水平均升高。此外,睾丸中ACE2/血管紧张素1-7/ MasR蛋白水平恢复,抑制了生殖细胞凋亡、脂质积累和氧化应激,并提高了睾酮合成相关蛋白水平。然而,MasR拮抗剂A779部分抵消了DIZE对DIO小鼠代谢和睾丸的改善作用。本研究表明,DIZE治疗通过激活ACE2/血管紧张素1-7/ MasR轴对肥胖诱导的睾丸损伤具有保护作用。