CYP2E1 Testis Expression and Alcoholmediated Changes of Rat Spermatogenesis Indices and Type I Collagen

Ganna M Shayakhmetova,Volodymyr V Ruschak,Larysa B Bondarenko,Valentina M Kovalenko

doi:10.2478/10004-1254-64-2013-2313

Abstract

This study is a complex investigation of alcohol-mediated changes in CYP2E1 mRNA and protein expression in the testes, as well as spermatogenesis indices and type I collagen amino acid contents, in male rats. Wistar albino male rats were divided into two groups: I--control (intact animals), II--experimental (chronic alcoholism, exposure to a 15% ethanol aqueous solution during 150 days). The destructive changes in the spermatogenic epithelium were accompanied by a decrease in sperm number and motility time. CYP2E1 mRNA and protein expression were elevated in the testes 3 and 1.4 times, respectively. Also, significantly lower contents of lysine, glutamic acid, serine, proline, alanine, valine, and phenylalanine residues accompanied by an increase of hydroxyproline, glycine, and threonine residue contents were detected in the skin type I collagen of the experimental group. Chronic ethanol consumption caused testicular failure along with an overexpression of CYP2E1 mRNA and protein in the testes as well as quantitative changes in type I collagen amino acid contents. The profound alcohol-mediated changes in collagen type I amino acid contents may have affected the spermatogenic epithelium state. The modulation of testicular cytochrome P450 2E1 mRNA and protein expression could change the functioning of this isozyme in target organs and take part in the mechanism of ethanol gonadotoxicity.

Highlights

This study is a complex investigation of alcohol-mediated changes in CYP2E1 mRNA and protein expression in the testes, as well as spermatogenesis indices and type I collagen amino acid contents, in male rats
The impairment of sperm quality in alcohol-dependent rats was accompanied by a development of destructive changes in their spermatogenic epithelium
Chronic ethanol selfadministration in male rats caused the development of testicular failure manifested by the deterioration of the quantitative and qualitative parameters of cauda epididymal sperm and destructive changes in the spermatogenic epithelium

Summary

Introduction

This study is a complex investigation of alcohol-mediated changes in CYP2E1 mRNA and protein expression in the testes, as well as spermatogenesis indices and type I collagen amino acid contents, in male rats. Alcohol abuse has a negative effect on all three factors that influence the male reproductive function: hypothalamus-hypophysis-gonads system, endocrine glands, and hormones [1] It is well-known that chronic alcohol dependence causes testicular abnormalities and sexual dysfunctions both in humans and animals [2, 3]; the exact mechanisms of ethanol-induced damage to the male reproductive organs remain unclear. Some investigations have demonstrated that acetaldehyde possesses greater toxicity than ethanol during testosterone production, directly inhibiting protein kinase C – a key enzyme in testosterone biosynthesis [9] It can cause changes in the pro- and antioxidants balances of testis cells [10]. Oxidative mechanisms can contribute to changes in collagen biosynthesis by triggering the release of pro-fibrotic cytokines and collagen gene expression in target cells [5]

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