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.
Subject(s)
Fluoxetine/pharmacology , Lactation , Maternal Exposure , Placenta/metabolism , Selective Serotonin Reuptake Inhibitors/pharmacology , Testis/drug effects , Testosterone/metabolism , Animals , Female , Male , Pregnancy , Rats , Testis/metabolismABSTRACT
In current assay the serotoninergic system in newly-born Wistar rats underwent pharmacological modification by fluoxetine, a selective serotonin reuptake inhibitor (SSRI), to investigate its repercussion on testicular parameters in adult animals. Thirty animals were distributed according to treatment: control animals (n = 6), animals treated with 1 mg kg-1 (n = 6), 5 mg kg-1 (n = 6), 10 mg kg-1 (n = 6) and 20 mg kg-1 (n = 6) of fluoxetine (IP). When 150 days old, the animals were anesthetized and perfused intra-cardiacally with fixative solution. Testes were routinely processed for inclusion in plastic resin (methacrylate glycol). Further, 4 µm-thick histological sections were stained with toluidine blue/sodium borate 1% and analyzed histometrically. Pharmacological intervention on the serotoninergic system during the postnatal period of the testes development in Wistar rats with fluoxetine chlorohydrate reduced parameters, such as testicular weight, testis liquid weight and seminiferous tubules diameter. However, testicular parameters, such as daily sperm production (DSP), spermatogenesis efficiency (DSP/g/testis) and cell population in stage VII of adult animals, were not influenced by fluoxetine chlorohydrate usage during neonatal period. Results show that administration of fluoxetine during 21 days after birth may induce adverse changes in the spermatogenesis of adult rats.
No presente trabalho, o sistema serotoninérgico de ratos Wistar recém-nascidos foi farmacologicamente modificado por um inibidor seletivo de recaptação da serotonina, fluoxetina, com o objetivo de observar sua repercussão nos parâmetros testiculares em ratos adultos. Trinta animais foram distribuídos de acordo com o tratamento: controle (n = 6), tratado com 1 mg kg-1 (n = 6), 5 mg kg-1 (n = 6), 10 mg kg-1 (n = 6) e 20 mg kg-1 (n = 6) de fluoxetina. Aos 150 dias de vida, os animais foram anestesiados e perfundidos intracardiacamente com solução fixadora. Os testículos foram removidos e processados para inclusão em resina plástica (glicol metacrilato). Cortes histológicos com 4 µm de espessura foram corados por azul de toluidina/borato de sódio 1% e analisados histometricamente. O tratamento com fluoxetina reduziu nos parâmetros de peso testicular líquido e bruto, bem como no diâmetro dos túbulos seminíferos. Entretanto, os parâmetros testiculares de produção espermática diária (PED), eficiência espermática (PED/g/testículo) e população de células germinativas no estágio VII não estavam alteradas pelo tratamento com fluoxetina. Em conclusão, a administração de fluoxetina durante 21 dias após o nascimento pode induzir efeitos adversos na espermatogênese de ratos adultos.