Could maternal exposure to the antidepressants fluoxetine and St. John's Wort induce long-term reproductive effects on male rats?

Department of Physiological Sciences, State University of Londrina - UEL, 86051-980, Londrina, Paraná, Brazil.
Reproductive Toxicology (Impact Factor: 2.77). 07/2012; 35. DOI: 10.1016/j.reprotox.2012.07.006
Source: PubMed

ABSTRACT Based on the limited number of studies that have investigated the adverse effects of maternal treatment with antidepressants on the development of male descendents, this study was carried out in rat in order to evaluate if maternal exposure to fluoxetine (FLX) or St. John's Wort (SJW) could disrupt the development of male offspring. The dams were treated daily, by gavage, with 7.5mg/kg of FLX or 100mg/kg SJW during pregnancy and lactation. The reproductive and behavior parameters were analyzed in male pups. Results showed decreases in the weight of the full seminal vesicle and in the number of spermatozoa. Moreover, FLX-exposed pups presented reduced seminiferous epithelium height and diameter of seminiferous tubules. The present study shows that maternal exposure to FLX, but not SJW could interfere on reproductive parameters in adult male rats.

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    ABSTRACT: Abstract Fluoxetine is a selective serotonin reuptake inhibitor used to treat depression in pregnant and nursing women. However, recent studies have shown adverse effects in the male reproductive system after fluoxetine treatment. Aiming to analyze the extent of damage caused by fluoxetine in the testicle and safe doses for treatment during the perinatal period, the present study analyzed the effects of in utero exposure and exposure during lactation to fluoxetine in spermatogenesis of male rat offspring in adulthood. Wistar rat dams were orally treated with fluoxetine (5, 10, and 20 mg/kg) from 13 days of gestation to lactation day 21 and their offspring were analyzed at 90 days old. Results showed a reduction in the weight of testes (16%), epididymis (28%), and seminal glands (18%) in animals exposed to fluoxetine 20 mg/kg compared to the control. Seminal gland weight was also reduced 25% and 30% in animals exposed to 5 mg/kg and 10 mg/kg fluoxetine, respectively. Body weight of animals exposed to 20 mg/kg fluoxetine was reduced from post-natal day 9 to 36 compared to controls but from the post-natal day 9 to 36 there was no statistical difference. The volume of seminiferous epithelium reduced 17% and the total volume of Leydig cells reduced 30% in the group exposed to fluoxetine at 20 mg/kg. Furthermore, Leydig cells volume reduced 29% in the 5 mg/kg group. The length of the seminiferous tubules reduced 17% and daily sperm production per testicle also reduced 18% in animals exposed to the highest dose of fluoxetine compared to controls. The individual area of Leydig cells increased 7% and plasma testosterone increased 49% in animals exposed to fluoxetine at 20 mg/kg. In conclusion, exposure to 20 mg/kg fluoxetine via the placenta and during lactation may change testosterone and testicular parameters important for sperm production and male fertility in adulthood.
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