Topiramate Impairs Spermatogenesis, Sperm Parameters, and Epididymal Duct Contractility in Rats

Abstract

Topiramate is a widely prescribed antiepileptic drug with a multimodal mechanism of action. However, its effects on male reproductive function remain poorly characterized. This study was conducted to investigate the impact of this drug on testicular and epididymal function in adult male Wistar rats. Animals were treated orally for 21 days with topiramate at 40 or 160 mg/kg. Serum testosterone levels, testicular histomorphology, spermatogenic indices, sperm parameters, and epididymal duct contractility were subsequently evaluated. The treatment did not alter serum testosterone levels at either dose. However, both doses reduced Sertoli cell and round spermatid numbers, increased primary spermatocyte counts, and decreased meiotic and overall spermatogenic yields, whereas only the higher dose (160 mg/kg) reduced Sertoli cell efficiency and daily sperm production. The lower dose (40 mg/kg) increased sperm morphological abnormalities, whereas the higher dose reduced total and progressive sperm motility and induced both head and tail defects. Additionally, treatment with topiramate at 160 mg/kg prolonged sperm transit time in the cauda epididymis and reduced contractile responses of the distal cauda epididymal duct to KCl, noradrenaline, and carbachol, suggesting impaired epididymal transport and potential ejaculatory dysfunction. Altogether, these findings demonstrate that topiramate adversely affects male reproductive function. Given its widespread use in individuals of reproductive age, these results underscore the need for translational studies in humans to assess potential reproductive risks associated with this therapy.