masterThesis
Efeitos dos antidepressivos fluoxetina e sertralina sobre parâmetros espermáticos e na contração do epidídimo de rato
Fecha
2020-10-09Registro en:
BEZERRA, Mayara Sâmala. Efeitos dos antidepressivos fluoxetina e sertralina sobre parâmetros espermáticos e na contração do epidídimo de rato. 2020. 77f. Dissertação (Mestrado em Ciências Biológicas) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2020.
Autor
Bezerra, Mayara Sâmala
Resumen
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.