Vitamin C Mitigates Potassium Perchlorate Exposure-Induced Disruption of Spermatogenesis in Medaka

Endocrine-disrupting chemicals (EDC) can cause metabolic and reproductive impairments. It is essential to develop strategies to mitigate EDC-exposure-induced endocrine disruption. Potassium perchlorate (KClO₄), widely used in industrial and military applications, is an emerging environmental contaminant known to disrupt thyroid function. Its potential impact on male reproductive health remains underexplored. In this study, we investigated the testicular impairments caused by chronic KClO₄ exposure in medaka (<i>Oryzias latipes</i>) and examined whether KClO₄-induced testicular impairment can be mitigated. Adult male medaka were treated with 0.01 mg/L KClO₄, 10 mg/L KClO₄, and 10 mg/L KClO₄ plus vitamin C (3 mg/L) and vitamin C (3 mg/L) alone for 21 days. Fertilization percentage, histological examination, and transcriptomic alterations in the testis were determined. KClO₄ exposure decreased fertilization success and caused disorganization of seminiferous tubules and dysregulated spermatogenic genes in the testis. Transcriptomic analysis revealed substantial dysregulation of genes involved in cadherin and tubulin binding, chromatin remodeling, oxidative stress response, and germ cell development. Coadministration of vitamin C mitigated these effects by restoring testicular morphology, restoring fertilization rates, and partially normalizing gene expression changes disrupted by KClO₄ exposure. The present findings suggest that vitamin C provides protective effects against KClO₄-induced testicular toxicity and highlight the need for further exploration of antioxidant-based interventions to safeguard reproductive health from KClO₄ exposure.