Polylactic Acid Micro/Nanoplastic Exposure Induces Male Reproductive Toxicity by Disrupting Spermatogenesis and Mitochondrial Dysfunction in Mice

Although considered an "eco-friendly" biodegradable plastic, polylactic acid (PLA) microplastic (PLA-MP) poses a growing concern for human health, yet its effects on male reproductive function remain underexplored. This study investigated the reproductive toxicity of PLA in male mice and its potential mechanisms. To this end, our in vivo and in vitro experiments demonstrated that after degradation in the digestive system, a significant number of PLA-MP-derived nanoparticles could penetrate the blood–testis barrier (BTB) and localize within the spermatogenic microenvironment. Mice exposed to PLA-MPs for a long time exhibited significant reproductive toxicity, evidenced by decreased sperm concentration and motility, increased sperm deformity rates, and disrupted sex hormone levels. Further analysis revealed that PLA impaired BTB, induced mitochondrial dysfunction in the testes, and triggered oxidative stress through excessive ROS production from mitochondria, leading to further testicular damage. Notably, PLA nanoplastics internalized in the mitochondrial sheath and disrupted the mitochondrial structure of sperm, causing dose-dependent impairments in mitochondrial function. Transcriptome analyses further indicated that PLA-MPs disrupted spermatogenesis by inhibiting the expression of key mRNA involved in this process. Collectively, our findings highlight the reproductive toxic effect of biodegradable PLA by damaging BTB and impairing mitochondrial function, which provides insights into the toxicological implications of biodegradable microplastics for mammalian fertility.