International Journal of Scientific & Engineering Research, Volume 6, Issue 5, May-2015 747 ISSN 2229-5518 IJSER © 2015 http://www.ijser.org EVIDENCE OF INCREASED OXIDATIVE STRESS AND DNA DAMAGES IN OLIGOSPERMIA Arun William, Viji Krishnan, Abdul Gafoor C, Apoorva M, Heera Banu C and Dinesh Roy D Abstract— Oligospermia is defined as a sperm density (count) less than 20 million/ml. Infertility affects approximately 15% of couples worldwide, among them 20–25% of reproductive problems being contributed to male factor. Male infertility is a relatively common condition affecting approximately 1 in 20 of the male population. Defective sperm function is held to be the largest, single and defined cause of human infertility. The excessive generation of reactive oxygen species (ROS) by abnormal spermatozoa has been defined as one of the important etiologies for male infertility. Generation and persistence of ROS in seminal fluid and sperm increase the rate of lipid peroxidation of sperm membrane which is manifested by a high MDA level. The present study was undertaken to evaluate the role of oxidative stress by measuring the level of oxidative stress marker, Malondialdehyde (MDA), in the sera of males suffering with oligospermia. The extent of somatic DNA damage in these subjects was quantified by using Cytokinesis Block Micronuclei Assay. These investigations were carried out in 56 subjects suffering with oligospermia and 15 healthy fertile men as control subjects. The MDA value and the micronuclei frequency was significantly elevated in study subjects as compared with that of control subjects. The finding of increased oxidative stress marker level may indicate that oxidative stress may be involved in the pathogenesis of sperm DNA damage leading to oligospermic condition as well as infertility in male subjects. These individuals can be better informed about the extent of somatic DNA damages, oxidative stress and genetic risks. This may help in preventing the sufferings of infertile subjects with oligospermia. Index Terms— DNA damages, Double strand breaks (DSB), Infertility, Malondialdehyde (MDA), Oligospermia, Oxidative stress, Reactive oxygen species (ROS), Sperm DNA integrity ——————————  —————————— 1 INTRODUCTION nfertility is defined as the failure to achieve a pregnancy within one year of regular (at least three times per month) unprotected intercourse [1]. It affects approximately 15% of couples worldwide, among them 20–25% of reproductive problems being contributed to male factor [2]. Male infertility is a relatively common condition affecting approximately 1 in 20 of the male population. In a vast majority of infertile sub- jects sufficient numbers of spermatozoa are generated to initi- ate a pregnancy; however, the functionality of the spermato- zoa has been compromised. As a result, defective sperm func- tion is held to be the largest, single and defined cause of hu- man infertility [3]. Oligospermia is defined as a sperm density (count) less than 20 million/ml [4] which may leads to male infertility [5]. ‘Male factor’ infertility is seen as an alteration in sperm concentration and/or motility and/or morphology [6]. Semen analysis remains the cornerstone in the evaluation of male infertility or oligospermia condition [5]. The primary causes of defective sperm function are undoubtedly multifac- torial, involving a range of primary genetic, lifestyle and envi- ronmental factors, acting alone or, more frequently, in combi- nation. At the level of the gamete, it is the oxidative stress that impairs the functional and structural integrity of these highly differentiated cells like sperm [7]. The oxidative stress not only disrupts the integrity of sperm DNA but also limits the fertilizing potential of these cells as a result of collateral damage to proteins and lipids in the sperm plasma membrane [7]. Oxidative stress is caused by an imbalance between pro-oxidants and anti-oxidants. This ratio can be altered by an increased level of reactive oxygen species or a decreased antioxidant defence mechanism [8]. Recombination is triggered by the generation of a DNA dou- ble strand break (DSB) within an amplicon. The occurrence of such lesions are particularly frequent in the male germ line, owing to the fact that spermatogenesis requires multiple cell divisions in an oxidative environment with depleted DNA repair enzymes [9]. Studies have also shown that elevated rate of DNA nicks and double strand breaks in sperm of infertile men could lead to infertility and 50% of miscarriages; this means that this individuals have a background of genetic in- stability that can be caused by their inability to repair DNA damage and are susceptible to mutagenic and clastogenic agents [10]. Sperm DNA damage is strongly associated with sperm function and infertility [11]. I ———————————————— • Arun William, Research Scholar, Meenakshi University,West K K Nagar, Chennai-600078 • Viji Krishnan,Department of Biochemistry, Jubilee Mission College and Re- search Institute, Thrissur-680005 • Apoorva M, Abdul Gafoor C, Heera Banu C and Dinesh Roy D, Genetika, Centre for Advanced Genetic Studies, Pettah P O, Thiruvananthapuram- 695024. IJSER