Gestational and lactational exposure to phthalates and nanoplastics induces inflammation and oxidative imbalance in the prostate of adult rats.

Abstract

The intrauterine microenvironment is highly susceptible to environmental disturbances, which may result in persistent effects on offspring health. Given that plastic-derived contaminants can cross the placental barrier and act as endocrine-disrupting chemicals, this study evaluated the effects of perinatal exposure to an environmentally relevant phthalate mixture (PM) and nanoplastics (NPs) on the prostate of adult rats. Pregnant Sprague-Dawley rats were allocated into 6 experimental groups: Ctrl (vehicle), T1 (20 μg/kg/d PM), T2 (200 mg/kg/d PM), T3 (NPs: 1.0 mg/kg/d), T4 (20 μg PM + NPs), and T5 (200 mg PM + NPs). Treatments were administered orally from gestational day 10 to postnatal day (PND) 21. Male offspring were euthanized on PND120, and ventral prostate samples were collected. Histological evaluation revealed increased inflammatory foci and stromal expansion in all exposed groups (T1-T5), along with reduced luminal compartment in T1, T3, and T4 compared with controls. All treated groups showed increased total and degranulated mast cells and enhanced androgen receptor immunoreactivity. Tumor necrosis factor (Tnf) expression was increased in all exposure groups, whereas Rela gene expression was elevated in the T4 and T5 groups. Oxidative stress analysis demonstrated increased lipid peroxidation and glutathione S-transferase (GST) activity in all treated animals. Catalase (CAT) activity was reduced in T1, T3, and T5, whereas superoxide dismutase (SOD) activity increased in T3, T4, and T5. Elevated levels of reduced, oxidized, and total glutathione (GSH, GSSG, tGSH) were observed in T5. Overall, perinatal exposure to PM and NPs induced persistent inflammation and altered redox status in the prostate, increasing susceptibility to pathological disorders.