Low-Dose Chlorothalonil Induces Testicular Injury Through Disruption of Steroidogenic Signaling in Adult Male Mice.

Abstract

Chlorothalonil (CHL) is a widely used organochlorine fungicide frequently detected in environmental and food matrices. Although increasing evidence indicates adverse effects in nontarget species, the mechanisms underlying CHL-induced male reproductive toxicity remain incompletely understood. This study investigated whether low-dose CHL exposure disrupts testicular redox homeostasis, endocrine regulation, and seminiferous epithelial organization in adult mice. Animals were exposed daily to CHL (1 or 10 mg/kg/day) by oral gavage for 50 consecutive days. Histological analyses revealed seminiferous epithelial alterations, including vacuolization, acidophilic cells, impaired spermatogenic progression, and a reduced proportion of histologically normal seminiferous tubules. These structural changes were accompanied by increased circulating testosterone and estradiol concentrations and by altered expression of steroidogenic enzymes and sex hormone receptors, indicating disruption of testicular steroidogenic signaling. CHL exposure also depleted testicular glutathione levels and increased total antioxidant capacity, whereas malondialdehyde and advanced oxidation protein products remained unchanged, indicating disruption of redox homeostasis without detectable oxidative damage. Notably, molecular and morphometric alterations were detected at the lower dose, whereas endocrine and histopathological changes were more pronounced at the higher dose. Collectively, these findings demonstrate that CHL disrupts testicular steroidogenic signaling, culminating in hormonal imbalance, impaired spermatogenic dynamics, and testicular injury. The present study provides mechanistic evidence supporting the endocrine-disrupting properties of CHL and identifies the testis as a sensitive target of its toxicity.