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Effects of Interferon Alpha on Reproductive Parameters of Male Rats, with Emphasis on Molecular Aspects of Blood-Testicular and Blood-Epididymal Barriers.

Grant number: 12/13307-4
Support type:Scholarships in Brazil - Master
Effective date (Start): October 01, 2012
Effective date (End): April 30, 2014
Field of knowledge:Biological Sciences - Morphology - Embryology
Principal Investigator:Wilma de Grava Kempinas
Grantee:Josiane de Lima Rosa
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Interferons (IFNs) are small proteins known for their antiproliferative and immunoregulatory activities and their crucial involvement in cellular antiviral action. The type I IFNs include IFN alpha, beta and omega that are used therapeutically in the treatment of various diseases such as metastatic melanoma, acuminata condyloma, Kaposi's sarcoma and hepatitis B and C. Studies indicate that IFN may be an endocrine disruptor with direct or indirect action on the male gonads. It's known that the drug can interfere on physiological function of the endothelial barrier and possibly in epithelial cells. The blood-testis barrier (HT) and blood-epididymal (HE) consist in tight junctions formed by adjacent epithelial cells of the seminiferous tubule or of the epididymal duct, respectively. These tight junctions are composed of several proteins, among them claudines (CLDNs), and the expression of different claudines along the seminiferous tubule and epididymal duct may represent a key element in the regulation changes of the intraluminal environment, that plays an essential role in reproductive functions. The aim of this study will be to investigate male reproductive parameters, with emphasis on the effects of INF alpha on molecular aspects of the barriers HT and HE. For this purpose, adult male Wistar rats (90 days) will be treated, subcutaneously, for 30 days, with IFN alpha and then evaluated for sperm parameters, hormone levels (luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone), and histological and morphometric analysis of testis and epididymis. Sperm quality will also be assessed by in utero artificial insemination . Molecular aspects of the HT and HE barriers will be evaluated by immunohistochemistry using marking of CLDN 3 and 11 in the testis and CLDN 1 and 3 in the epididymis. Besides the preparation of qualified human resources in Biology and Toxicology of Reproduction, we expect to acquire new knowledgement on the effects of interferon alpha on reproductive parameters of male rats, disseminating the results in publications in international journals, as well in communications in scientific events of this area. Moreover, to establish collaboration with internacional researchers in the area do Biology and Toxicology of Reproduction.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ROSA, JOSIANE DE LIMA; CAVARIANI, MARILIA MARTINS; BORGES, CIBELE DOS SANTOS; ARAUJO LEITE, GABRIEL ADAN; ANSELMO-FRANCI, JANETE APARECIDA; KEMPINAS, WILMA DE GRAVA. LACK OF REPRODUCTIVE TOXICITY IN ADULT MALE RATS EXPOSED TO INTERFERON-ALPHA. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, v. 78, n. 20, p. 1288-1298, OCT 18 2015. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.