Prenatal road traffic noise impairs early testicular development in Sprague-Dawley offspring: pharmacological rescue by melatonin and edaravone; developmental preservation by environmental enrichment.

Road traffic noise (RTN), an emerging environmental stressor, has been linked to adverse gestational outcomes; however, its impact on offspring early reproductive development and potential pharmacological interventions remain insufficiently explored. Oxidative stress and inflammation are considered key mechanisms underlying prenatal stress-induced developmental programming. The current study aims to investigate whether maternal administration of melatonin (MLT) and edaravone (EDV), individually or in combination, can protect against prenatal RTN-induced early testicular development in male offspring and to assess environmental enrichment (EE) as an independent non-pharmacological approach to preserve normal reproductive development. Pregnant Sprague-Dawley rats were randomly assigned to six groups: control, RTN (100 dB(A) SPL), RTN + MLT (5 mg/kg/day, i.p.), RTN + EDV (5 mg/kg/day, i.p.), RTN + MLT + EDV, and EE (independent). Male offspring were evaluated on postnatal day 21 for reproductive organ weights; testicular oxidative stress markers (TBARS and NO₂⁻); antioxidant enzymes (GSH, SOD, and CAT); inflammatory cytokines (TNF-α and IL-6); serum testosterone levels; and testicular histopathological changes. Prenatal RTN exposure was found to be a significant cause of reduced reproductive organ weights, testosterone concentrations, and antioxidant enzyme activities, while increasing lipid peroxidation, nitro-oxidative stress, and pro-inflammatory cytokine levels. The combined gestational administration of MLT and EDV conferred superior restoration of prenatal RTN-induced adverse redox homeostasis, inflammatory status, and testicular structure of offspring compared with either agent alone. However, providing environmental enrichment alone during the gestational period avoided adverse reproductive programming in offspring. The findings identify RTN as a modifiable prenatal environmental risk factor and suggest MLT and EDV as promising pharmacological strategies for mitigating RTN-associated early testicular developmental alterations. Independently, optimized gestational EE was associated with favorable early testicular development. These findings warrant further mechanistic and translational investigation.