The Potential Risks of Biodegradable Plastics: Professor Jiang Hui's Team at Peking University Reports for the First Time on the Reproductive Toxicity Induced by Polylactic Acid Micro/Nanoplastics

The widespread use of plastics has significantly contributed to the advancement of industrial civilization and economic development, but it has also led to severe environmental pollution, particularly due to microplastics (MP) and nanoplastics (NP) that have become ubiquitous in human environments. Existing studies show that the average human intake of microplastic particles is approximately 0.1 to 5 grams per week, raising concerns about the potential health risks.

To mitigate plastic pollution, biodegradable plastics have been introduced as environmentally friendly alternatives to traditional petroleum-based plastics. Polylactic acid (PLA) is the most widely produced and consumed biodegradable plastic globally, used in food packaging, Disposable Tableware, and as a carrier for drug delivery in biomedical applications. While PLA is considered an "eco-friendly" plastic, studies have shown that its ingestion may cause inflammation, and PLA may generate more microplastics during degradation than traditional petroleum-based plastics, indicating potential risks that warrant further investigation.

On January 27, 2025, Professor Jiang Hui's team at Peking University First Hospital published a research paper in the authoritative materials science journal ACS Nano, titled "Polylactic acid micro/nanoplastic exposure induces male reproductive toxicity by disrupting spermatogenesis and mitochondrial dysfunction in mice." This study for the first time revealed the reproductive toxicity of PLA micro/nanoplastics (PLA-MP/NP) in male mice, suggesting that the toxic mechanisms may be similar to those of traditional petroleum-based microplastics. These findings provide a theoretical basis for assessing the environmental risks of biodegradable plastics.

Infertility is a global public health issue and the third leading obstinate disease worldwide, after cancer and cardiovascular diseases. Oligozoospermia (low sperm count) is one of the primary causes of male infertility, and environmental pollution is considered a significant factor contributing to reduced male fertility. As a result, the effects of environmental pollutants on reproductive health have become a subject of widespread concern. Previous studies by Jiang Hui's team have confirmed the presence of microplastics in the male reproductive system, and it has been shown that traditional petroleum-based polystyrene (PS) microplastics can cause testicular damage in prepubertal males, threatening fertility. However, little is known about the effects of PLA on male reproductive function. Therefore, the research team conducted a 56-day repeated oral toxicity study in mice using environmental-relevant doses (10 mg/kg/d, 100 mg/kg/d) and hazard-identification doses (1000 mg/kg/d) of PLA microplastics (PLA-MP) to explore the reproductive toxicity of PLA-MP exposure in male mice.

The results showed that PLA-MP, after being absorbed into the body, penetrated the blood-testis barrier through the bloodstream and accumulated in the testicular microenvironment. This accumulation induced significant reproductive toxicity, including a reduction in sperm count, decreased sperm motility, increased sperm deformities, and hormonal imbalances. Moreover, histopathological examination revealed degeneration of seminiferous tubules, loss of germ cells, and disruption of reproductive epithelial tissue. Notably, the enlargement of the spermatogenic space and the complete disappearance of sperm in some seminiferous tubules indicated severe structural damage to the testis. These findings support the hypothesis that PLA-MP exposure induces reproductive toxicity in male mice.

Mitochondrial dysfunction is a critical mechanism of toxicity induced by environmental pollutants, and mitochondrial damage is considered a key mechanism of microplastic-induced toxicity. The study found that after PLA-MP exposure, particles were internalized and accumulated in the mitochondria of cells. The internalized PLA-MP caused morphological changes in the mitochondria, such as swelling, increased size, vacuolization, and the formation of tubular cristae, along with the appearance of mitochondrial autophagosomes. Reactive oxygen species (ROS) levels, an important indicator of oxidative stress, were found to increase in a dose-dependent manner, and mitochondrial dysfunction induced by elevated ROS levels further exacerbated oxidative stress, creating a vicious cycle of continuous mitochondrial damage. To assess the impact of PLA-MP exposure on mitochondrial function, the team evaluated indicators of mitochondrial integrity, including Ca2+ levels, ATP production, and mitochondrial membrane potential (MMP) in GC-2 spermatocytes. The results showed that PLA-MP exposure reduced MMP and ATP levels while significantly increasing intracellular Ca2+ levels, suggesting that mitochondrial dysfunction could be a sensitive indicator of PLA-MP-induced reproductive toxicity.

The mitochondrial sheath is a critical component of the sperm tail, essential for maintaining sperm motility. Structural abnormalities in the mitochondrial sheath can lead to male infertility. To investigate whether PLA particles penetrate sperm and cause mitochondrial sheath damage, the research team used transmission electron microscopy to observe the ultrastructure of sperm midpieces. As expected, they found that a certain number of nanometer-sized PLA particles adhered to the sperm midpiece. Notably, PLA nanoparticles even penetrated the sperm interior and reached the mitochondrial sheath, participating in the process of mitochondrial disintegration. In addition, PLA disrupted the redox homeostasis inside the sperm and triggered oxidative stress, resulting in damage to both the structure and function of sperm mitochondria.

To further investigate the molecular mechanisms underlying the reproductive toxicity induced by PLA-MP, the research team performed transcriptomic analysis of the testicular tissue from the high-dose exposure group. The results revealed that PLA-MP significantly downregulated the expression of several key genes related to spermatogenesis (e.g., C3, Pde7b, Wt1, and Dkk3) and affected pathways associated with mitochondrial function, such as calcium ion transport. These findings suggest that PLA-MP exposure leads to impaired spermatogenesis and worsens reproductive toxicity by inhibiting the expression of key genes involved in sperm development.

In conclusion, this study provides the first evidence that polylactic acid (PLA) micro/nanoplastics induce reproductive toxicity in male mice by disrupting spermatogenesis and causing mitochondrial dysfunction. The results demonstrate that PLA microplastics penetrate the blood-testis barrier, accumulate in the testicular microenvironment, and induce oxidative stress, hormone imbalances, and testicular developmental disorders in mice. Furthermore, the degradation of PLA microplastics into nanoplastics can penetrate sperm mitochondria, causing mitochondrial damage, suggesting that mitochondrial dysfunction is a key mechanism and early indicator of PLA-induced reproductive toxicity.

Overall, this research enhances our understanding of the toxicological effects of biodegradable microplastics on human health and provides new insights for evaluating the health risks of biodegradable plastics. As PLA is commonly promoted as an "environmentally friendly" plastic, its bio-transformation, bio-distribution, and potential toxicological effects in humans warrant further attention.

Corresponding authors of the paper include Professor Jiang Hui from Peking University First Hospital, Professor Zhang Zhe from Peking University Third Hospital, and Dr. Li Yuanyuan from the Institute of Ecology and Environmental Sciences, Chinese Academy of Sciences. Dr. Zhao Qiancheng from Peking University First Hospital is the first author, with Dr. Fang Zishui (postdoctoral researcher) and Dr. Wang Pengcheng (Peking University Third Hospital) as co-first authors.