Abstract
Microplastics (MPs), as emerging contaminants, may adversely affect male reproductive health. This study investigated the potential association between MP accumulation in human semen and sperm quality. Furthermore, the molecular mechanisms underlying MPs-induced sperm quality impairment were characterized using representative polystyrene microplastics (PS-MPs), murine models, and spermatogonial cell cultures. Among 200 semen samples, the overall detection rate of MPs was 55.5% (111/200). A total of 128 MPs were identified in semen, with PS (32.03%) and PVC (36.72%) being the predominant microplastic polymers. Epidemiological analyses revealed a significant positive association between plastic tableware (PT) use frequency and MP accumulation in semen. Stratified analyses further revealed a strong association between total MPs exposure and reduced sperm concentration among individuals with BMI < 24 kg/m² and frequent PT use. In murine models, exposure to PS-MPs induced reduced sperm quality, elevated sperm abnormalities, and increased levels of autophagy and apoptosis. Mechanistically, PS-MPs activated the MAP3K1/p38/c-fos pathway via the transcription factor FOXA1, thereby inducing the autophagy and apoptosis of spermatogonia. Collectively, this study provides direct human evidence that MP accumulation in semen is associated with impaired sperm quality, particularly in individuals with certain lifestyle factors such as frequent PT use. Moreover, our findings further demonstrate the potential reproductive toxicity of MPs and, for the first time, elucidate the critical role of the FOXA1/MAP3K1/p38 cascade in PS-MPs-mediated decline in sperm quality.