Diminazene aceturate, an ACE2 activator, ameliorates testicular injury in diet-induced obese mice.

IF 3.7 3区生物学 Q1 DEVELOPMENTAL BIOLOGY

Reproduction Pub Date : 2025-02-07 Print Date: 2025-03-01 DOI:10.1530/REP-24-0242

Xiaofeng Yue, Rui Yin, Liling Wu, Jinjin Li, Jianwu Wang, Benhuang Yan, Lingyong Dai, Chongxing Shen, Yi Zhi, Ling Wan, Jigao Yang, Weibing Li

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Abstract

In brief: 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.

Abstract: 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.

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乙酰氨基苯乙酯，ACE2激活剂，改善饮食诱导的肥胖小鼠睾丸损伤。

DIZE改善了DIO小鼠的肥胖和代谢紊乱。经DIZE治疗后，精子数量和活力增加，形态改善，男性生育能力增加。血清和睾丸内睾酮水平均有所升高。同时，恢复睾丸组织中ACE2/Ang 1-7/MasR蛋白水平，抑制生殖细胞凋亡、脂质积累和氧化应激，提高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。结论：DIZE治疗通过激活ACE2/Ang 1-7/MasR轴对肥胖致睾丸损伤具有保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Reproduction 生物-发育生物学

CiteScore

7.40

自引率

2.60%

发文量

199

审稿时长

4-8 weeks

期刊介绍： Reproduction is the official journal of the Society of Reproduction and Fertility (SRF). It was formed in 2001 when the Society merged its two journals, the Journal of Reproduction and Fertility and Reviews of Reproduction. Reproduction publishes original research articles and topical reviews on the subject of reproductive and developmental biology, and reproductive medicine. The journal will consider publication of high-quality meta-analyses; these should be submitted to the research papers category. The journal considers studies in humans and all animal species, and will publish clinical studies if they advance our understanding of the underlying causes and/or mechanisms of disease. Scientific excellence and broad interest to our readership are the most important criteria during the peer review process. The journal publishes articles that make a clear advance in the field, whether of mechanistic, descriptive or technical focus. Articles that substantiate new or controversial reports are welcomed if they are noteworthy and advance the field. Topics include, but are not limited to, reproductive immunology, reproductive toxicology, stem cells, environmental effects on reproductive potential and health (eg obesity), extracellular vesicles, fertility preservation and epigenetic effects on reproductive and developmental processes.