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: 3.23).
07/2012; 35(1). DOI: 10.1016/j.reprotox.2012.07.006
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.
Available from: Alice Hartmann Dos Santos
- "Rats were kept in a controlled environment at 21 AE 28C under a 12-h light–dark cycle (lights on at 0600 hours) and had free access to regular laboratory chow and tap water. Rats were mated (two females and one male per cage) and the morning on which spermatozoa were found in the vaginal smear was designated Gestational Day (GD) 0. Dams were divided into two groups: (1) a control (CTR) group, in which 10 dams were given 0.25 mL tap water (by oral gavage) daily from GD0 to Lactational Day (LD) 21; and (2) a FLX-treated group in which 12 dams received 7.5 mg kg À1 FLX (Daforin liquid; Novaquimica, Hortolândia, SP, Brazil) by oral gavage daily from GD0 to LD21 (Lisboa et al. 2007; Vieira et al. 2013b). The dose of FLX used in the present study was based on the weight of dams on GD0 because in humans dose is not corrected according to weight fluctuations during gestational and lactational periods. "
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ABSTRACT: Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI) antidepressant commonly prescribed during pregnancy and lactation. Pre- and post-partum depression, as well as SSRI treatment during these periods, may change maternal care, interfering with offspring development. Moreover, it is known that SSRIs may alter testes structure and function in offspring. The present study investigated the effects of maternal FLX exposure on maternal behaviour and testes function in offspring. Female Wistar rats were treated with 7.5mgkg-1 FLX or tap water (control group) by gavage from the Day 1 of pregnancy until 21 days after birth (postnatal Day (PND) 21). Maternal behaviour was evaluated and morphofunctional analyses of offspring testes were conducted on PND 21 and 50. There were no significant differences between the FLX-treated and control groups regarding maternal behaviour. Nor did maternal treatment with FLX have any effect on bodyweight gain, anogenital distance, day of preputial separation, testis weight and the gonadosomatic index in male offspring. However, there was a decreased number of Sertoli cells at both PND 21 and 50 in FLX-exposed male offspring. The findings of the present study demonstrate that maternal exposure to FLX can impair testicular function in weanling and pubertal animals.
Available from: Rosana Nogueira de Morais
- "In addition, sexual development, estrous cyclicity, daily sperm production and testicular morphometry and cell counts evaluated in rat offspring exposed in utero and during lactation to fluoxetine were not affected, even at the highest dose tested, although other studies have shown that this antidepressant may affect some reproductive parameters. Studies in rodents showed that fluoxetine treatment decreased male fertility   and may impact the reproductive development of male offspring after maternal exposure . "
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ABSTRACT: The present study evaluated the reproductive effects of fluoxetine exposure in utero and during lactation on pregnancy outcomes and the sexual development of offspring. Pregnant Wistar rats were treated daily with fluoxetine (0.4, 1.7 and 17 mg/kg/day) or distilled water by gavage from gestation day (GD) 7 to lactation day (LD) 21. A significant reduction in maternal body weight was observed during pregnancy and lactation in dams exposed to 17 mg/kg fluoxetine. Hormone analysis revealed an increase in progestagen and glucocorticoid metabolites on GD 15 and estrogen and progestagen metabolites on LD 7 in dams treated with 17 mg/kg fluoxetine. Estrogen metabolites also were increased on LD 7 in dams treated with 0.4 mg/kg fluoxetine. Besides that, an increase in the weight of the adrenal glands and a reduction in uterine weight in dams exposed to highest dose of fluoxetine was observed. Finally, pup birth weight and the viability and weaning indices also were reduced in animals exposed to 17 mg/kg fluoxetine. Overall, maternal hormonal changes were only observed at the highest dose tested, which also induced maternal and foetal toxicity. No significant changes were seen in dams or offspring exposed to therapeutic-like doses.
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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.
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