Effects of Fluoxetine and Sertraline on sperm parameters and epididymis contraction
Fluoxetine; Sertraline; Distal cauda of epididymis; sperm parameters.
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 “anti-fertility” 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 aims to evaluate the effects of two of most clinically used antidepressants (fluoxetine and sertraline) on sperm parameters and epididymis contraction. We have used segments of distal cauda epididymis from male adult Wistar rats to evaluate the in vitro effects of fluoxetine or sertraline on contractions induced by agonists (carbachol or phenylephrine) or KCl. In addition, male adult Wistar rats were treated for 21 days with fluoxetine 20 mg/kg/day (i.p.), sertraline 20 mg/kg/day (i.p.) or drug free vehicle. At the end of the treatment, the animals were euthanized and the blood collected for testosterone dosage. Testis and epididymis were isolated for determination of sperm parameters: sperm production, sperm transit time and sperm count throughout epididymis. Segments of distal cauda epididymis were also used to check the effects of in vivo treatment with both drugs on spontaneous or drug induced contractions. The in vitro incubation of fluoxetine or sertraline (> 3 μM) reduced the contractions of the distal cauda epididymis induced by KCl, carbachol or phenylephrine. We also found that fluoxetine 1 μM was able to potentiate the epididymis contractions induced by phenylephrine. In addition, in vivo treatment with fluoxetine or sertraline for 21 days significantly reduced the daily sperm production, the sperm count in the epididymis and accelerated the sperm transit in cauda of epididymis. In vivo treatment with both drugs was also able to drastically reduce serum testosterone levels, increase spontaneous contractions of the distal cauda epididymis and potentiate the contractions induced by the adrenergic agonist phenylephrine. In conclusion, changes in the motor activity of the epididymis may be associated with the anti-fertility effects of fluoxetine or sertraline.