Assessment of female fertility and oocyte quality in mice after exposure to polystyrene microplastics and polybrominated diphenyl ethers, alone and in combination.

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.