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

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.