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Structural evaluation of seminiferous tubules and steroidogenic activity of Leydig cells in venlafaxine-treated rats

Grant number: 18/13590-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2018
Effective date (End): August 31, 2019
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Estela Sasso Cerri
Grantee:Beatriz Meduqui Rodrigues
Home Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

It is known that male fertility depends on the spermatogenic success, and spermatogenesis is a complex process, which depends on hormones, mainly testosterone provided by Leydig cells. Moreover, the Sertoli cells maintain an adequate microenvironment in the seminiferous epithelium for the spermatogenic process via androgenic action. Damage to these testicular somatic cells, induced by drugs, may impair the testicular histophysiology and disturb spermatogenesis, culminating in infertility. Depression is a serious disease that has affected a high number of people, leading to a high consumption of antidepressants. Venlafaxine is a new-generation antidepressant of the class of the selective serotonin and noradrenaline reuptake inhibitors (SNRIs). Besides the treatment and prevention of depression, this drug is also used for the treatment of anxiety, social anxiety disorder, panic disorder and agoraphobia. However, in venlafaxine-treated men, erectile dysfunction, ejaculation disorders and reduction of serum testosterone levels have been reported. Despite of the high antidepressants consumption, few is known about the effect of these drugs on the male reproductive system, including spermatogenesis and steroidogenesis. In this study, the testicular histophysiology of male rats following the treatment with venlafaxine will be evaluated, focusing on the seminiferous epithelium integrity and steroidogenic activity of Leydig cells. Twelve adult male rats will be distributed into two groups (n=6): Control group (CG35) e Venlafaxine group (VFG35). The animals from VFG35 will receive, by gavage, 30mg/kg of venlafaxine chlorydrate (diluted in water) for 35 days, whereas CG will receive water. After the treatment, testes will be collected, weighed and fixed in buffered 4% formaldehyde for paraffin and historesin embedding. Blood samples will be collected for the measurement of serum testosterone levels. In the H.E.-stained historesin sections, morphological and morphometric analyses will be performed. In the seminiferous tubules sections, the area of the total tubular section and the epithelial area will be measured, and the number of Sertoli cells will be quantified. The frequency of tubules showing asynchronous seminiferous epithelium and/or failure of spermatid release will be computed. The paraffin sections will be submitted to TUNEL method for detection of cell death, and to immunofluorescence for detection of StAr, a protein involved in steroidogenesis. The differences between the groups will be statistically analyzed by the Student-t test (pd0.05).