HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 71/4/1309    most recent biolreprod.104.028407v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal My Folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Williams, A.C. Articles by Ford, W.C.L. Search for Related Content PubMed PubMed Citation Articles by Williams, A.C. Articles by Ford, W.C.L. Agricola Articles by Williams, A.C. Articles by Ford, W.C.L.

Functional Significance of the Pentose Phosphate Pathway and Glutathione Reductase in the Antioxidant Defenses of Human Sperm¹

University Division of Obstetrics & Gynaecology, St Michael's Hospital, Bristol BS2 8EG, United Kingdom

Glutathione peroxidase is one of the principal antioxidant defense enzymes in human spermatozoa, but it requires oxidized glutathione to be reduced by glutathione reductase using NADPH generated in the pentose phosphate pathway. We investigated whether flux through the pentose phosphate pathway would increase in response to oxidative stress and whether glutathione reductase was required to protect sperm from oxidative damage. Isotopic measurements of the pentose phosphate pathway and glycolytic flux, thiobarbituric acid assay of malondialdehyde for lipid peroxidation, and computer-assisted sperm analysis for sperm motility were assessed in a group of normal, healthy semen donors. Applying moderate oxidative stress to human spermatozoa by adding cumene hydroperoxide, H₂O₂, or xanthine plus xanthine oxidase or by promoting lipid peroxidation with ascorbate increased flux through the pentose phosphate pathway without changing the glycolytic rate. However, adding higher concentrations of oxidants inhibited both the pentose phosphate pathway and glycolytic flux. At concentrations of 50 µg/ml or greater, the glutathione reductase-inhibitor 1,3-bis-(2-chloroethyl) 1-nitrosourea decreased flux through the pentose phosphate pathway and blocked the response to cumene hydroperoxide. It also increased lipid peroxidation and impaired the survival of motility in sperm incubated under 95% O₂. These data show that the pentose phosphate pathway in human spermatozoa can respond dynamically to oxidative stress and that inhibiting glutathione reductase impairs the ability of sperm to resist lipid peroxidation. We conclude that the glutathione peroxidase-glutathione reductase-pentose phosphate pathway system is functional and provides an effective antioxidant defense in normal human spermatozoa.

¹ Supported by a grant from the Wellcome Trust.

² Correspondence: W.C.L. Ford, University Division of Obstetrics & Gynaecology, St Michael's Hospital, Southwell Street, Bristol BS2 8EG, U.K. FAX: 44 117 9285290; chris.ford{at}bristol.ac.uk

This article has been cited by other articles:

				J. O. Kromer, C. J. Bolten, E. Heinzle, H. Schroder, and C. Wittmann Physiological response of Corynebacterium glutamicum to oxidative stress induced by deletion of the transcriptional repressor McbR Microbiology, December 1, 2008; 154(12): 3917 - 3930. [Abstract] [Full Text] [PDF]

				K. Tremellen Oxidative stress and male infertility--a clinical perspective Hum. Reprod. Update, May 1, 2008; 14(3): 243 - 258. [Abstract] [Full Text] [PDF]

				R.J. Aitken, J. K. Wingate, G. N. De Iuliis, and E. A. McLaughlin Analysis of lipid peroxidation in human spermatozoa using BODIPY C11 Mol. Hum. Reprod., April 1, 2007; 13(4): 203 - 211. [Abstract] [Full Text] [PDF]