Avaliação dos efeitos da trazodona sobre parâmetros reprodutivos e contração do ducto epididimário de ratos

Abstract

Trazodone is an antidepressant approved for the treatment of major depressive disorder with a low incidence of causing sexual dysfunction. However, its effects on male reproductive health are not yet fully understood. Therefore, this study aimed to evaluate the effects of trazodone on reproductive parameters and the contraction of the distal cauda epididymal duct in rats. Adult Wistar rats were orally treated for 21 days with saline (control) or trazodone at doses of 10 mg/kg and 20 mg/kg. After treatment, the animals were euthanized, and blood was collected to determine testosterone levels. The reproductive organs were isolated and weighed. Testes were used for histomorphological evaluation, measurement of MDA and GSH levels, and assessment of parameters such as daily sperm production. The epididymis were used to evaluate sperm parameters, including sperm count in the head/body and cauda regions, sperm transit time through different epididymal segments, motility, viability, and morphology. The contraction of the isolated distal cauda epididymal duct was also assessed. In silico studies were conducted to predict molecular targets related to the effects of trazodone and its active metabolite on the male reproductive tract. The results indicated that trazodone induced anti-reproductive effects in rats, evidenced by testicular tissue damage, increased intratesticular lipid peroxidation, and reduced sperm production and sperm count in various epididymal regions. Additionally, trazodone treatment reduced progressive sperm motility, the number of viable sperm, and the number of morphologically normal sperm, indicating decreased sperm quality. The contraction of the isolated distal cauda epididymal duct was also impaired by in vivo and in vitro trazodone treatment, suggesting possible alterations during the emission phase of ejaculation. Moreover, both trazodone and its active metabolite exhibited in silico predictors suggesting nonspecific interactions with pharmacological targets, which may contribute to an unfavorable reproductive toxicological profile. In conclusion, trazodone exhibited significant anti-reproductive effects that may impair male fertility.