Impact of precise modulation of reactive oxygen species levels on spermatozoa proteins in infertile men.

Ahmet Ayaz,Mohamed Arafa,Rakesh Sharma,Ashok Agarwal,Haitham Elbardisi,Zhihong Cui

doi:10.1186/1559-0275-12-4

Ahmet Ayaz, Mohamed Arafa + Show 4 more

Open Access

https://doi.org/10.1186/1559-0275-12-4

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Journal: Clinical Proteomics	Publication Date: Feb 9, 2015
Citations: 43	License type: cc-by

Affiliation: Cleveland Clinic, Hamad General Hospital

Abstract

BackgroundElevated levels of reactive oxygen species (ROS) are detected in 25% to 80% of infertile men. They are involved in the pathology of male infertility. Understanding the effect of increasing levels of ROS on the differential expression of sperm proteins is important to understand the cellular processes and or/pathways that may be implicated in male infertility. The aim of this study was to examine differentially expressed proteins (DEPs) in spermatozoa from patients with low, medium and high ROS levels.MethodsA total of 42 infertile men presenting for infertility and 17 proven fertile men were enrolled in the study. ROS levels were measured by chemiluminescence assay. Infertile men were divided into Low (0- < 93 RLU/s/106 sperm) (n = 11), Medium (>93-500 RLU/s/106 sperm) (n = 17) and High ROS (>500 RLU/s/106 sperm) group (n = 14). All fertile men had ROS levels between 4-50 RLU/s/106 sperm. 4 subjects from fertile group and 4 each from the Low, Medium and High ROS were pooled. Protein extraction, protein estimation, gel separation of the proteins, in-gel digestion, LTQ-orbitrap elite hybrid mass spectrometry system was conducted. The DEPs, the cellular localization and pathways of DEPs involved were examined utilizing bioinformatics tools.Results1035 proteins were identified in the 3 groups by global proteomic analysis. Of these, 305 were DEPs. 51 were unique to the Low ROS group, 47 Medium ROS group and 104 were unique to the High ROS group. 6 DEPs were identified by Uniprot and DAVID that had distinct reproductive functions and they were expressed only in 3 ROS groups but not in the control.ConclusionsWe have for the first time demonstrated the presence of 6 DEPs with distinct reproductive functions only in men with low, medium or high ROS levels. These DEPs can serve as potential biomarkers of oxidative stress induced male infertility.Electronic supplementary materialThe online version of this article (doi:10.1186/1559-0275-12-4) contains supplementary material, which is available to authorized users.

Highlights

Elevated levels of reactive oxygen species (ROS) are detected in 25% to 80% of infertile men
We have for the first time demonstrated the presence of 6 differentially expressed proteins (DEPs) with distinct reproductive functions only in men with low, medium or high ROS levels
These DEPs can serve as potential biomarkers of oxidative stress induced male infertility

Summary

Introduction

Elevated levels of reactive oxygen species (ROS) are detected in 25% to 80% of infertile men. When used in conjunction with conventional semen analysis, oxidative stress can help differentiate between fertile and infertile men, as well as help to identify a subgroup of infertile men who may benefit from antioxidant supplementation [7]. Factors such as lifestyle (smoking), environmental (pesticide, air pollution, electromagnetic radiation), and health (chemotherapy, urogenital infection, prostatitis) can significantly alter the balance between ROS levels and total antioxidant capacity, disrupt sperm plasma membrane fluidity, impair sperm motility and induce sperm DNA damage [3,7]

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