Subchronic low-dose tributyltin exposure is associated with parallel hypothalamic IL-10 suppression and ovarian inflammatory–endocrine alterations in female rats

Tributyltin (TBT) is a persistent environmental endocrine disruptor with documented neurotoxic and reproductive effects, yet its impact on coordinated brain–ovary immune–endocrine regulation remains unclear. This study investigated whether subchronic, low-dose TBT exposure is associated with parallel alterations in these tissues. Female Wistar rats were exposed to TBT (50, 100, 300 ng/kg/day) with or without fucoxanthin (Fx, 20 mg/kg/day) for four weeks. Brain and ovarian tissues were assessed via histopathology, immunohistochemistry (NF‑κB, IL‑6, IL‑1β, IL‑10, ERα, PR), and RT‑qPCR (TNF‑α, Adipoq). TBT exposure was associated with reduced central IL‑10 alongside increased NF‑κB/IL‑1β/IL‑6 and neurodegenerative changes. Concurrently, ovaries showed NF‑κB/IL‑6 activation, altered TNF‑α/Adipoq expression, follicular degeneration, and disrupted ERα/PR signaling. These dose‑dependent, non‑linear effects occurred simultaneously in both tissues. Fx co‑treatment mitigated many alterations, partially restoring IL‑10, suppressing inflammatory markers, and improving ovarian histopathology. These findings indicate that subchronic low-dose TBT exposure is associated with parallel brain–ovary immune–endocrine-related alterations, supporting the concept that endocrine disruptors can perturb integrated central–peripheral immune–endocrine networks without implying direct endocrine dysfunction.