Juvenile and Pubertal Exposure to Polystyrene Nanoplastics Impairs Epididymal Structure and Sperm Quality in Mice

Nanoplastics (NPs) are emerging environmental contaminants capable of crossing biological barriers, accumulating in tissues, and disrupting physiological pathways. The male reproductive system is particularly vulnerable during the postnatal period, a developmental window characterized by intense testicular differentiation and epididymal maturation. This study investigated whether exposure to polystyrene nanoplastics (PS-NP) during the juvenile and pubertal periods alters epididymal morphophysiology and sperm quality in C57BL/6 male mice. Animals (postnatal day, PND 22) received PS-NP orally at doses of 0.1 mg/day (PS-NP1X) or 1 mg/day (PS-NP10X) for 50 consecutive days. Body and epididymal weights showed no significant differences among groups. However, stereological analyses revealed marked epididymal remodeling, particularly in the caput segment, characterized by increased epithelial compartment volume and reduced stromal and luminal compartments in animals exposed to the higher dose. Leukocyte infiltrates were detected in both epididymal regions, suggesting inflammatory activation. Cytokine quantification indicated region- and dose-dependent imbalances between pro- and anti-inflammatory mediators, reflecting disrupted local homeostasis. PS-NP exposure reduced the percentage of morphologically normal sperm in both exposed groups and decreased total motile sperm in the high-dose group. Mitochondrial activity assessment revealed a higher proportion of sperm lacking mitochondrial function, indicating impaired energetic metabolism. In contrast, sperm viability and chromatin maturation remained unaffected. Together, these findings demonstrate that PS-NP exposure during postnatal development induces epididymal structural alterations, inflammatory dysregulation, and functional impairments in sperm quality, reinforcing the heightened vulnerability of this developmental window to plastic-derived contaminants.