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Impact of the antidepressant venlafaxine in the somatic testicular cells and germ cells viability of adult rats

Grant number: 19/09064-8
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2019
Effective date (End): August 31, 2020
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Estela Sasso Cerri
Grantee:Marcio José Viana Pinheiro Junior
Home Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Introduction: The seminiferous tubules are composed of a specialized epithelium containing germ cells and somatic cells (Sertoli cells - SC) named seminiferous epithelium. SC are responsible for the structural and nutritional maintenance of germ cells, producing a number of important substances, such as transferrin, an iron carrier, an indicator of the function of these cells. The maintenance of the seminiferous epithelium depends on testosterone, a steroid hormone produced by Leydig cells (LC). Therefore, changes in SC and or LC may induce significant changes in the spermatogenic process and hence in fertility. Venlafaxine is an antidepressant of the class of selective serotonin and noradrenaline reuptake inhibitors, used in the treatment of depressive disorder, anxiety disorder, panic syndrome and social phobia. Clinical studies have shown that this drug causes sexual dysfunction, decrease in testosterone levels and gynecomastia. However, there is no data in the literature on the effects of venlafaxine on the male reproductive system. Objectives: In the present study, the impact of venlafaxine on the histophysiology of the testes will be evaluated in adult rats, focusing on the germ cell viability and the functional integrity of SC and LC. We will also evaluate whether drug-induced testicular changes are reversed after discontinuation of treatment for 30 days. Methods: Twenty-four adult Holtzman male rats will be distributed into 4 groups (n = 6). The Venlafaxine-35 days (GVF-35) and Venlafaxine-65 days (GVF-65) groups will receive 30mg/kg b.w. of venlafaxine hydrochloride (diluted in distilled water) by gavage for 35 consecutive days. The Control-35 days (GC-35) and Control-65 days (GC-65) groups will receive distilled water. After 35 days of treatment, the animals from the GC-35 and GVF-35 groups will be euthanized, while the animals from the GC-65 and GVF-65 groups will remain 30 days without treatment before euthanasia. The testes will be collected, fixed and processed for inclusion in historesin and paraffin. In the historesin sections of the animals from all groups stained by H.E., the number of SC per tubule will be quantified, and the nuclear diameters of LC will be measured. Paraffin sections will be subjected to the TUNEL method for detection of cell death, as well as to the immunofluorescence reaction for detection of transferrin protein. For comparison of results between groups, all data will be submitted to Two-Way ANOVA, followed by the Tukey statistical test (pd0.05).