Role of Art1 in Sperm Damage Induced by Type 2 Diabetes Mellitus

ABSTRACT Diabetes‐associated spermatogenic dysfunction remains mechanistically unclear despite its clinical significance. We aimed to elucidate the effect and molecular mechanism of sperm damage induced by type 2 diabetes mellitus (T2DM). In a mouse model of T2DM, transcriptome sequencing identified Art1 as a differentially expressed gene. T2DM induced structural damage to the seminiferous tubules, deregulated sperm parameters, and suppressed Art1 expression in mice and caused reproductive damage in their offspring. Danshensu administration rescued these pathologies. In vitro , high‐glucose/high‐lipid exposure induced GC‐2 cell damage, while Art1 overexpression reduced oxidative stress and apoptosis. Art1 ‐knockout mice exhibited impaired sperm motility and tubule structural defects, confirming Art1 's critical role in spermatogenesis maintenance. This study demonstrated that T2DM triggers testicular oxidative stress, apoptosis, and Art1 suppression, leading to transgenerational reproductive dysfunction. Experiments have shown that the overexpression of Danshensu or Art1 can rescue these pathological damages. The results from the Art1 ‐knockout mice confirm the indispensable regulatory role of Art1 in spermatogenesis maintenance. We speculate that T2DM may impair male reproductive ability by inhibiting the expression of Art1 , which will provide a new molecular target and theoretical basis for further investigation into the interaction mechanism between T2DM and the reproductive system.