ABSTRACT
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.
Subject(s)
Rats , Fluoxetine , Sertoli Cells , SpermatogenesisABSTRACT
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 -21st day to calculate daily doses of fluoxetine. 5 mg (T1), 10 mg (T2) 20 mg (T3) or deionized water, were injected intraperitoneally. On the 21st 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 21st 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.
El propósito del presente estudio fue probar la hipótesis que el uso de fluoxetina - un inhibidor altamente selectivo de la serotonina (SSRI) - induce cambios en el desarrollo testicular de ratas durante el período de amamantamiento. Los grupos de ratas macho recién nacidas fueron asignados aleatoriamente con diversas dosis del fluoxetina, 24 horas después del nacimiento. Cada cría permanecía con su madre respectiva durante 21 días. El peso corporal (BW) fue medido diariamente desde el 21día 1 al 21, para calcular las dosis diarias del fluoxetina. 5 mg (T1), 10 mg (T2) y 20 (T3) o agua desionizada fueron inyectados intraperitonealmente. En el día 21, los animales fueron tratados con heparina, anestesiados y la sangre fue recogida por punción cardiaca para determinar por radioinmunoanálisis los niveles de la hormona folículo-estimulante (FSH). Los testículos fueron retirados, pesados y procesados para el análisis morfométrico. Los grupos tratados con fluoxetina presentaron disminución del tamaño y peso testiculares, en comparación con el grupo control día 21. Los resultados demuestran que la manipulación del sistema serotoninérgico con fluoxetina durante el período crítico del desarrollo testicular, altera la población de células de Sertoli y todos los parámetros testiculares relacionados con este tipo celular.