Assessment of female fertility and oocyte quality in mice after exposure to polystyrene microplastics and...

With the extensive use of plastics and brominated flame retardants, polystyrene microplastics (Ps-MPs) and polybrominated diphenyl ethers (PBDEs) frequently co-occur in the environment, raising growing concerns about their combined reproductive hazards. However, the synergistic toxicity of Ps-MPs and PBDEs on female fertility and oocyte quality remains insufficiently characterized. In this study, we established a 28-day oral exposure model in female ICR mice to evaluate the effects of Ps-MPs, PBDE-47, and their co-exposure on ovarian function, oocyte meiotic competence, and reproductive outcomes. Both Ps-MPs and PBDE-47 alone reduced ovarian weight, decreased antral follicles, increased follicular atresia, and markedly lowered ovulation and litter size, whereas co-exposure produced the most severe impairments. At the oocyte level, exposure significantly reduced germinal vesicle breakdown and first polar body extrusion, increased abnormal spindle formation and erroneous kinetochore-microtubule attachments, and suppressed TPX2 expression and α-tubulin acetylation. Cortical F-actin polarization, spindle migration, and membrane localization of JUNO and ovastacin were also disrupted, indicating widespread defects in meiotic and membrane maturation. Mechanistically, Ps-MPs and PBDE-47 induced a decline in mitochondrial membrane potential, aberrant mitochondrial distribution, excessive lipid accumulation, and Ca²⁺ imbalance, accompanied by autophagosome accumulation, lysosomal dysfunction, elevated ROS, increased γ-H2AX signals, and enhanced Annexin V labeling, ultimately triggering DNA damage and apoptosis. All alterations were most pronounced under co-exposure. Collectively, Ps-MPs and PBDE-47 synergistically impair female fertility by converging on mitochondrial dysfunction, autophagy-lysosome imbalance, and oxidative stress-mediated DNA damage, leading to substantial reductions in oocyte quality. These findings provide key mechanistic evidence for evaluating reproductive risks associated with real-world mixtures of microplastics and persistent organic pollutants.