Epididymal toxicity of deoxynivalenol: Age-specific effects in prepubertal and adult mice.

Deoxynivalenol (DON), a mycotoxin produced by Fusarium species that contaminates agricultural commodities worldwide, is known for its deleterious effects on male reproduction. Although hormonal, testicular, and sperm alterations have been described, the effects of DON on the epididymis, an organ essential for sperm maturation and storage, remain underexplored. This study evaluated DON-induced epididymal toxicity in prepubertal and adult mice. Sixty animals were fed a DON-contaminated diet (10 mg DON/kg feed) or a mycotoxin-free diet for 15 or 28 days, respectively. Stereological, histological, and immunohistochemical (E-cadherin, caspase-3, and androgen receptor) analyses were conducted, together with assessments of oxidative stress, inflammatory profile, sperm count, and transit time. In prepubertal mice, DON exposure altered epididymal compartment proportions, increasing stromal areas in the caput and cauda, expanding the cauda epithelium, and reducing luminal spaces. Histological changes included an increased number of tubules without sperm and interstitial fibrosis, accompanied by decreased FRAP levels and reduced macrophage number, TNF-α, and IL-1β expression. In adult mice, DON reduced stromal area in the caput, increased stromal and decreased luminal compartments in the cauda, and induced epithelial vacuolization, fibrosis, and apoptosis, along with reduced TNF-α levels. These findings demonstrate that DON disrupts epididymal development in prepubertal mice; however, longitudinal studies are required to evaluate its long-term consequences. In adults, DON may impair fertility through tissue remodeling and inflammatory modulation. The observed reduction in pro-inflammatory mediators may represent a potential therapeutic pathway; however, further studies are required to clarify the reproductive risks and mechanisms underlying DON exposure.