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

Abstract

Due to the widespread use of fluoxetine to treat depression, including pregnant and nursing women, the present study aimed to investigate the effects of in utero and lactational exposure to fluoxetine in rat offspring at post natal day 22. Wistar rat dams were orally treated with fluoxetine (5, 10, and 20 mg/kg) from day 13 gestation to day 21 lactation. Exposure to 10 and 20 mg/kg fluoxetine reduced the body and testis weights. The volume of the seminiferous tubules and epithelium were also reduced following 20 mg/kg fluoxetine exposure. The length of the seminiferous tubules and the population of Sertoli cells changed in offspring exposed to fluoxetine. The amount of seminiferous tubules lacking tubular lumen was higher in rats exposed to 20 mg/kg fluoxetine. Plasma testosterone showed no significant change. In conclusion, fluoxetine exposure via the placenta and lactation may inhibit and delay testicular development, adversely affecting several testicular parameters important for the establishment of sperm production in adulthood.

Antenatal exposure to the selective serotonin reuptake inhibitor fluoxetine leads to postnatal metabolic and endocrine changes associated with type 2 diabetes in Wistar rats

“…In the present study we have shown that fetal and neonatal exposure to fluoxetine resulted in a significant increase in body weight in the female but not in the male offspring; these changes occurred in the absence of altered postnatal food consumption despite the fact that fluoxetine has been shown to affect food consumption in adult rodents (Lauzurica et al, 2013). Moreover, although other experiments in rats have reported a reduction in birth weight following fluoxetine exposure during pregnancy (de Oliveira et al, 2013;Müller et al, 2013) we did not observe any effect of fluoxetine in altering birth weight in our study, suggesting that the metabolic deficits in this model are independent of impaired fetal growth. Although the mechanism(s) underlying the sex-specific differences in body composition are unknown, sex-specific differences in the long-term effects of prenatal exposure to SSRIs and childhood overweight have also been reported in human studies (Grzeskowiak et al, 2013).…”

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

“…The reduction in these parameters shown in our study also indicates a reduction in fertility after exposure to fluoxetine. Oliveira et al [2013] also observed a reduced volume of seminiferous tubules and epithelium after exposure to fluoxetine at 20 mg/kg via placenta and lactation. Moreover, germ cells and Sertoli cells are located in seminiferous epithelium [Holstein et al 2003], considering that the population of Sertoli cells did not change, the present study also indicates an effect of fluoxetine on germ cells.…”

“…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 Mendes-da-Silva et al [2002], Silva Junior et al [2008], and Oliveira et al [2013], the exposure to fluoxetine reduced the body weight of 21 day postnatal (pre-puberty) rat. It is interesting to note that Silva Junior et al [2013] showed no change in body weight in adult animals.…”

“…SSRI exposure may induce maternal and fetal toxicity and reduce male sexual behavior in adult rats [Harris et al 2012;Müller et al 2013], as well as impair sexual motivation in adult male mice [Gouvêa et al 2008]. 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].…”