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Late effects of moderate chronic stress, induced from peripuberty, on the reproductive parameters of adult rats treated with escitalopram or not

Grant number: 19/08785-3
Support type:Regular Research Grants
Duration: August 01, 2019 - July 31, 2021
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Sandra Maria Miraglia Valdeolivas
Grantee:Sandra Maria Miraglia Valdeolivas
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Assoc. researchers:Maria Martha Bernardi ; Samara Urban de Oliva

Abstract

The incidence of infertility affects around 15% of couples worldwide. The male factor is directly or indirectly involved in approximately 50% of these cases. Many factors with diverse etiologies can cause sexual disturbances, affect spermatogenesis and lead to male infertility, including those caused by xenobiotics. The number of adolescents with psychiatric disorders, including depression, has been increasing dramatically. Antidepressants and antipsychotics drugs are used in the treatment of neuropsychiatric disorders depending on the various indications and may be recommended in therapy of adults as well as children and adolescents. Depression and anxiety represent about 80% of psychiatric disorders and can occur in young patients. Emotional stress has been pointed out as an additional risk factor for male idiopathic infertility. Escitalopram, a selective serotonin reuptake inhibitor (SSRI), is often prescribed in the treatment of symptoms associated with autism, major depression, and other psychiatric disorders, providing significant improvement in symptoms of anxiety, mood, and invasive developmental disorders. Escitalopram has been approved by the FDA for the treatment of psychiatric disorders in children and adolescents. SSRIs can cause side effects, including on reproduction, such as erectile dysfunction and reduced libido. Few experimental studies have evaluated the role of moderate chronic stress and escitalopram treatment on sperm parameters, especially during the period from peripuberty to adulthood. Thus, it was decided to investigate the reproductive alterations in adult rats that will be submitted to moderate unpredictable chronic stress for 8 weeks, from peripuberty (41 days postpartum, DPP) to adult phase (97 DPP), which will be or will not be treated with escitalopram for 5 weeks from the 70th PPD. The animals will be submitted to appropriate tests to verify ECMI according to the literature (forced swimming test and consumption of 1% sucrose solution). The experimental groups are the following: a) Moderate Chronic Stress (GE) group; b) Escitalopram group (Ge, 10 mg / kg, per gavage); c) GEe group, Moderate Chronic Stress + Escitalopram-treated (GEe) group; d) Sham Control group (SC), treated with 0.9% physiological solution by gavage. Quantitative and qualitative sperm parameters, genotoxicity through the analysis of sperm DNA fragmentation and chromatin structure (Comet, Acridine Orange and Chromomycin A3 assays), fertility index, reproductive capacity and sexual behavior will be investigated. Plasma testosterone and corticosterone measurements (ELISA method) and oxidative stress level, through the dosages of testicular and epididymal malondialdehyde, will be investigated. Testicular histopathology will be evaluated. The data obtained will be compared to each other and subjected to adequate statistical tests. (AU)