Neonatal Administration of Fluoxetine Decreased Final Sertoli Cell Number in Wistar Rats

Abstract

SUMMARY:The aim of the present study was to test the hypothesis that the application of fluoxetine -a highly selective serotonin reuptake inhibitor (SSRI) -in rats during the suckling period induces changes in testicular development. Groups of newborn male rats were randomly assigned with different doses of fluoxetine 24 hours after birth. Each litter stayed with its respective mother during 21 days. Body weight (BW) was measured daily from the 1st -21 st day to calculate daily doses of fluoxetine. 5 mg (T1), 10 mg (T2) 20 mg (T3) or deionized water, were injected intraperitoneally. On the 21 st day, animals were heparinized, anesthetized and blood was collected by cardiac puncture to determine by radioimmunoassay the follicle stimulating hormone (FSH) levels. Testis were removed, weighed, and processed for morphometric analysis. Fluoxetine groups presented decreased body and testicular weight when compared with the control group on the 21 st day. Our findings show that the manipulation of the serotoninergic system with fluoxetine during the critical period of testicular development alters the Sertoli cell population and all testicular parameters related to this cell.

Fluoxetine induces changes in the testicle and testosterone in adult male rats exposed via placenta and lactation

“…Previous studies published by our research group showed a reduction in the Sertoli cell population after intraperitoneal treatment with fluoxetine 5, 10, and 20 mg/kg [Silva Junior et al 2008] and exposure to 20 mg/kg fluoxetine via the placenta and lactation [Oliveira et al 2013] in young animals. However, in the present study and according to Silva Junior et al [2013], the Sertoli cell population in adulthood did not change after perinatal exposure to fluoxetine.…”

“…According to França et al [2005], testosterone has a great role for the maintenance of quantitatively normal spermatogenesis. It is interesting to note that treatment with 10 mg/kg fluoxetine from post-natal days 1 to 21 also reduced plasma FSH levels [Silva Junior et al 2008]. Furthermore, human patients treated with SSRI showed changes in serum levels of LH, FSH, and testosterone [Safarinejad 2008], moreover exposure to fluoxetine at 17 mg/kg may increase progestagen and glucocorticoid metabolites in gestation and lactation [Müller et al 2013].…”

“…Also, SSRI exposure via placenta and lactation may inhibit the testicular development in prepubertal rats and decrease the number of spermatozoa in adult rats [Oliveira et al 2013;Vieira et al 2012]. Adult male rats treated with SSRI also showed changes in spermatogenesis and Sertoli cell population [Aggarwal et al 2012;Silva Junior et al 2008;Silva Junior et al 2013]. Furthermore, the blockage of the serotoninergic system in prepubertal rats inhibits spermatogenesis development [Aragón et al 2005].…”

Perinatal exposure to fluoxetine via placenta and lactation inhibits the testicular development in male rat offspring

“…On post natal day 22, a reduction in body weight was observed in all treatment groups. Studies previously demonstrated that intraperitoneal administration of citalopram and fluoxetine can reduce body weight gain of neonate rats [Mendes da Silva et al 2002;Deiró et al 2004;Silva Junior et al 2008]. This change could be related to the inhibitory effect of serotonin on food ingestion [Simansky 1996].…”

“…Moreover, the long half-life of these compounds can contribute to a sustained exposure of fetuses and neonates [Heikkinen et al 2003]. Possible adverse effects of these drugs have been studied in rat offspring treated during pregnancy, lactation, or early postnatal life [Pereira et al 2007;Silva Junior et al 2008].…”