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

I n their recent study, Zhao et al. report on the reproductive toxicity and underlying mechanisms of polylactic acid (PLA) microplastics/nanoplastics (PLA-MPs) in male mammals. 1 The authors demonstrate that orally administered PLA-MPs can degrade into nanoplastics in the digestive system, cross the blood-testis barrier (BTB), and accumulate within spermatogenic cells and sperm.These particles disrupt spermatogenesis, reduce sperm quality, and impair hormone levels.Notably, the study links PLA-MP exposure to mitochondrial dysfunction, oxidative stress, and structural damage in testicular and sperm mitochondria.Transcriptomic analyses further reveal downregulation of key genes involved in spermatogenesis.The authors focused primarily on the toxic effects of PLA-MPs in the reproductive system, while providing limited discussion on the degradation of ingested PLA.PLA is an ecofriendly, readily biodegradable material that degrades into lactic acid.When evaluating the in vivo toxicity of PLA, it is essential to consider the potential confounding factors introduced by the metabolism of its degradation products.PLA is an aliphatic polyester that undergoes degradation primarily through the hydrolysis of ester bonds without requiring enzyme participation (nonenzymatic hydrolysis).While nonenzymatic hydrolysis occurs, enzymatic activity, particularly from certain proteases and lipases, can significantly accelerate PLA degradation under physiological conditions.Degradation rates are influenced by multiple factors, including the chemical structure, molecular weight, crystallinity, environmental conditions (temperature, pH, microorganisms, etc.), and whether it is blended with other polymers. 2 In an aqueous environment (such as phosphate-buffered saline at 37 °C and pH 7.4), PLA has a slow degradation rate. 3 In vivo, PLA degradation is further influenced by enzyme activity, cellular responses, and local physiological conditions. 4 Studies indicate that PLA implants degrade over 1 to 5 years with mass loss and molecular weight reduction, depending on the implantation site and material properties.Additionally, it has been shown that acidic degradation products can induce a mild inflammatory response. [5][6]][7] Lactate serves as a critical energy source for male germ cells.It is primarily produced by Sertoli cells, transported via monocarboxylate transporters (MCTs), and utilized by germ cells for ATP production. 8Lactate also serves as a significant signaling molecule in Sertoli cells, modulating proliferation and survival pathways such as MAPK and PI3K-AKT.In the male