Differential parental exposure to polystyrene microplastics from weaning period to maturity: Immune homeostasis dysregulation in F1 offspring.

The effects of long-term parental microplastic exposure on offspring immunity remain unclear. This study investigated how different parental exposure patterns affect immune status in F1 offspring. Parental rats were divided into four groups: paternal, maternal, dual-parental, and control. Treated groups received polystyrene microplastics (5 mg/L) in drinking water for 90 days. F1 offspring were raised under standard conditions until 8 weeks of age, after which fecal samples, thymus, spleen, and serum were collected for immune evaluation. Maternal microplastic exposure significantly disrupted gut microbiota α-diversity, dysbiosis index, and composition in F1 offspring (all P < 0.05). These changes were accompanied by decreased RBCs and PLT counts, elevated serum TNF-α, reduced thymic CD3+ and CD4+ T cells, and downregulated IL-10 mRNA and NF-kB protein expression. Histological examination revealed blurred corticomedullary boundaries, sparse cellularity, and lymphocyte vacuolization in the thymus, along with thinning of the periarteriolar lymphatic sheaths in the spleen, further indicating immune imbalance. Paternal and dual-parental exposure also induced gut microbiota dysbiosis and reduced thymic CD4+ T cells. Paternal exposure upregulated Th17-related RORγt and TNF-α mRNA in the thymus, whereas dual-parental exposure decreased thymic Nrf2 protein, splenic CD4+/CD8+ ratios, and white pulp area. Thymic pathology was observed in both groups. In conclusion, our findings suggest that prolonged parental exposure to microplastics may disrupt immune homeostasis in F1 offspring by altering gut microbiota composition and modulating oxidative stress or inflammatory responses. Moreover, the extent of these effects varies with the different parental exposure patterns.