Efeitos dos antidepressivos fluoxetina e sertralina sobre parâmetros espermáticos e na contração do epidídimo de rato

Abstract

It is widely described that antidepressants (including fluoxetine and sertraline) presents negative effects on male sexual function and semen quality. However, the exact mechanism behind the “antifertility” effects of antidepressants remains elusive. We speculate that these drugs could induce direct effects on epididymis, altering its motor activity and, then, sperm parameters as epididymal transit or sperm counts in different parts of the epididymis. Thus, our work was conducted in order to evaluate the effects of two of most clinically used antidepressants (fluoxetine and sertraline) on sperm parameters and epididymal duct contractions. We have used segments of epididymal duct isolated from distal cauda epididymis of male adult Wistar rats in an attempt to evaluate the in vitro effects of fluoxetine or sertraline on contractions induced by agonists (carbachol or phenylephrine) or KCl. In addition, male adult Wistarrats were also treated for 21 days with fluoxetine 20 mg/kg/day (i.p.), sertraline 20 mg/kg/day (i.p.) or drug free vehicle (DMSO 20%). At the end of the treatment, the animals were euthanized and the blood collected for testosterone dosage. Testis and epididymis were also isolated for determination of sperm parameters: sperm production, sperm transit time and sperm count throughout epididymis. Segments of epididymal duct from distal cauda epididymis were also used to check the effects of in vivo treatment with both drugs on spontaneous or drug induced contractions. In vitro incubation of fluoxetine 3 and 10 μM reduced the epididymal duct contractions induced by KCl (~30 and ~70%, respectively), carbachol (~50 and ~75%, respectively) or phenylephrine (~50 e ~80%, respectively). We were also found that pre-exposition to fluoxetine 1 μM increased the phenylephrine potency by about 3-fold while fluoxetine 10 μM significantly decreased the potency of phenylephrine and carbachol by 5,5 and 7,5-fold. respectively. The in vitro incubation of sertraline 3 and 10 μM reduced the epididymal duct contractions with similar fashion to the fluoxetine. Sertraline 10 μM also decreased the potency of phenylephrine and carbachol by about 3 and 5- fold, respectively. Thus, we found that in vivo treatment with fluoxetine and sertraline diminished the daily sperm production (~40 and 30%, respectively), sperm count in epididymis (caput/body: 60 and 55%, respectively; cauda: ~60% for both drugs) and accelerated the sperm transit time through cauda epididymis (~40% for both drugs). The rats exposed to fluoxetine and sertraline for 21 days also presented a reduction in serum testosterone levels (~60 and ~55%, respectively), an increase in the frequency (Control: 0.31 ± 0.15, n = 10; Fluoxetine: 2.27 ± 0.48, n = 8, P <0.05; Sertraline: 0.95 ± 0.28, n = 8, P> 0.05) and amplitude (Control: 0.026 ± 0.015, n = 10; Fluoxetine: 0.15 ± 0.02, n = 8, P <0.05; Sertraline: 0.11 ± 0.02, n = 8, P<0.05) of the epididymal duct spontaneous contractions. The potency of phenylephrine was increased by 3 and 2.5-fold in the epidydimal duct of distal cauda epididymis from rats treated with fluoxetine and sertraline, respectively. In conclusion, changes in the motor activity of the epididymis may be associated with the antifertility effects of fluoxetine or sertraline.