Oxidation of Sperm DNA and Male Infertility

Abstract

One important reason for male infertility is oxidative stress and its destructive effects on sperm structures and functions. The particular composition of the sperm membrane, rich in polyunsaturated fatty acids, and the easy access of sperm DNA to oxidative damage due to sperm cell specific cytologic and metabolic features (no cytoplasm left and cells unable to mount stress responses) make it the cell type in metazoans most susceptible to oxidative damage. In particular, oxidative damage to the spermatozoa genome is an important issue and a cause of male infertility, usually associated with single- or double-strand paternal DNA breaks. Various methods of detecting sperm DNA fragmentation have become important diagnostic tools in the prognosis of male infertility and such assays are available in research laboratories and andrology clinics. However, to date, there is not a clear consensus in the community as to their respective prognostic value. Nevertheless, it is important to understand that the effects of oxidative stress on the sperm genome go well beyond DNA fragmentation alone. Oxidation of paternal DNA bases, particularly guanine and adenosine residues, the most sensitive residues to oxidative alteration, is the starting point for DNA damage in spermatozoa but is also a danger for the integrity of the embryo genetic material independently of sperm DNA fragmentation. Due to the lack of a spermatozoa DNA repair system and, if the egg is unable to correct the sperm oxidized bases, the risk of de novo mutation transmission to the embryo exists. These will be carried on to every cell of the future individual and its progeny. Thus, in addition to affecting the viability of the pregnancy itself, oxidation of the DNA bases in sperm could be associated with the development of conditions in young and future adults. Despite these important issues, sperm DNA base oxidation has not attracted much interest among clinicians due to the lack of simple, reliable, rapid and consensual methods of assessing this type of damage to the paternal genome. In addition to these technical issues, another reason explaining why the measurement of sperm DNA oxidation is not included in male fertility is likely to be due to the lack of strong evidence for its role in pregnancy outcome. It is, however, becoming clear that the assessment of DNA base oxidation could improve the efficiency of assisted reproductive technologies and provide important information on embryonic developmental failures and pathologies encountered in the offspring. The objective of this work is to review relevant research that has been carried out in the field of sperm DNA base oxidation and its associated genetic and epigenetic consequences.

Oxidative Stress and Male Fertility: Role of Antioxidants and Inositols

“…At the same time, this high amount of PUFA represents a risk for the spermatozoa, being PUFA vulnerable to lipid peroxidation (LPO) [19]. The oxidative damage that can result is associated with the loss of membrane fluidity, mitochondrial dysfunction, alteration of morphology, reduction of vitality and other alterations that lead to the failure of fertilization [6].…”

“…When the antioxidant system fails to counteract the excessive increase in ROS, cell death occurs. Therefore, ROS have a double role: physiologically to complete the maturation of spermatozoa and/or to achieve fertilization, but in excess they are harmful to cell structures, functions and survival [6].…”

“…Furthermore, the main target of ROS is the peroxidation of unsaturated fatty acids that produces highly reactive lipid and aldehyde, which in a positive feedback react with cellular components producing increasing ROS contents [6,25].…”

“…Lifestyle [6,7], genetics [8] and environment, such as exposure to chemicals [9], represent risk factors for male infertility. Additionally, several pathologies may cause infertility, including varicocele and endocrine unbalance, all related to oxidative stress and DNA damage [6].…”

Morin-5′-Sulfonic Acid Sodium Salt (NaMSA) Attenuates Cyclophosphamide-Induced Histological Changes in Genitourinary Tract in Rats—Short Report

“…There are still not too many possibilities to counteract these drug-induced complications. Among many reasons of decreased fertility or even infertility such as anatomical pathologies, diabetes, obesity, smoking, cancers, radiation or environmental toxins, adverse effects of many anticancer agents are very important [1][2][3].…”