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Effect of venlafaxine on the male reproductive histophysiology and sperm parameters of adult rats

Grant number: 17/19829-6
Support type:Regular Research Grants
Duration: February 01, 2018 - January 31, 2020
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Estela Sasso Cerri
Grantee:Estela Sasso Cerri
Home Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Assoc. researchers:Flávia Luciana Beltrame ; Paulo Sergio Cerri

Abstract

Depression has affected million people worldwide and the antidepressant drugs, such as selective serotonin-norepinephrine reuptake inhibitors (SNRIs), have been clinically prescribed. Male patients treated with venlafaxine, a SNRI, has demonstrated reduced serum testosterone levels and erectile and ejaculatory dysfunctions. However, studies about the effect of venlafaxine on the histophysiology of testes and epididymis as well as on the spermatic parameters have not been found in the literature. The aim of this study is to evaluate the structural and functional integrity of the testes, epididymis and sperm parameters in adult rats treated with venlafaxine. Sixty male adult rats will be distributed into four groups: (n=15): Venlafaxine-30 days (VF-30); Control-30 days (C30); Venlafaxine-30+35 days (VF-30+35) and Control-30+35 days (C30+35). The animals from VF30 and VF30+35 will receive oral dosages of 30mg/kg b.w. of venlafaxine for 30 days. The animals from C30 e C30+35 will receive distilled water. After the treatment, the animals from VF30 e C30 will be killed, while the animals from VF30+35 and C30+35 will be maintained without treatment for 35 more days before euthanasia (period necessary for the completion of spermatogenesis and the sperm transit to the cauda epididymis). Sperm will be collected from the epididymis cauda for the analysis of sperm parameters. The testes and epididymides will be weighed and embedded in paraffin and historesin for morphological and morphometric analyses. Testicular and epididymal fragments will be frozen for molecular analyses. Intratesticular levels of testosterone and levels of serum testosterone, LH and FSH will be evaluated. In the testicular sections, the tubular and epithelial areas will be measured and the number of Sertoli cell and spermatogonia will be quantified. In the sections of cauda epididymis, the minor diameter of the epididymal duct and epithelial height will be measured, and the birefringent collagen will be quantified. TUNEL method will be performed in the testicular and epididymal sections. Immunofluorescence will be performed for detection of transferrin (Sertoli cell marker), c-kit (spermatogonia marker), StAR (Leydig cell marker), CRISP1 and V-ATPase (epididymal epithelial cell markers). These protein levels will also be evaluated by Western blot. The expression of conexin 43 (protein of hematotesticular barrier), ndrg2 (Leydig cell apoptosis), crisp1 (principal cell marker) and serpin-2 (androgenic control of epididymal duct) will be evaluated by real time RT-PCR. The differences among the groups will be statistically analyzed (p<0,05). (AU)