Polylactic acid microplastic exposure induced male reproductive toxicity and decreased testosterone levels by accelerating Leydig cell senescence

Polylactic acid microplastics (PLA-MPs), despite being marketed as biodegradable and eco-friendly alternatives to conventional plastics, have raised growing concerns regarding their potential adverse effects on human health. The reproductive toxicity of PLA-MPs exposure in male mammals has been confirmed in previous studies, but its specific effects on testosterone biosynthesis remain unclear. Male mice were treated with PLA-MPs at doses of low, medium, and high (0.01, 0.1, and 1 mg/d, respectively) for a duration of 28 days in this study. Our results demonstrated that PLA-MPs were enriched in mouse testes and led to a dose-dependent decrease in the serum testosterone concentration. We also observed the accumulation of senescent Leydig cells in the testis, along with inhibited autophagy and mitophagy. Moreover, we identified the critical involvement of autophagy and mitophagy in PLA-MPs-induced Leydig cell senescence. Re-establishment of autophagy and mitophagy effectively reserved the senescence of Leydig cell. Overall, our study revealed that PLA-MPs inhibit autophagy and mitophagy, thereby promoting Leydig cell senescence and subsequently reducing testosterone synthesis and secretion. These results advance our understanding of the pathogenic mechanisms underlying PLA-MPs-induced reproductive toxicity in male mammals.