Sperm DNA damage diagnostics: when and why

tau.amegroups.com © Translational Andrology and Urology. All rights reserved. Sperm DNA damage is the major cause of defective sperm function. DNA damage includes DNA denaturation and sperm DNA fragmentation (SDF) and maybe the common underlying aetiology of infertility, recurrent spontaneous abortion (RSA) preand post-implantation losses, accelerated aging, and childhood cancer (1). Oxidative DNA damage is an important factor, which affects sperm quality and increases risk of genetic and epigenetic abnormalities. Accumulation of oxidized DNA adducts like 8 hydroxy2deoxyguanosine (8OHdG) can impair function of denovo methylases and result in genome wide hypomethylation which compromise genetic stability (2). Thus, loss of sperm DNA integrity not only impacts reproductive and psychological health of the infertile couple but also increases childhood disease burden. Maintenance of integrity of germ cells is therefore crucial for fertility and success in assisted reproductive technologies and for the health and well being of the next generation. SDF occurs due to various factors like persistence of nicks created during meiosis, spermiogenesis/improper compaction, a ltered histone protamine rat io and abortive apoptosis (3). In addition, oxidative stress due to endogenous and various exogenous factors is one of the leading causes of DNA damage and is the major cause of loss of integrity of both mitochondrial and nuclear genome (4). It is therefore important to not only quantify the levels of SDF/DNA damage but also to determine the levels of 8OHdG to better define the aetiology of DNA damage. The latter will confirm that SDF is oxidative in nature and it will be possible to reduce oxidative stress by appropriate lifestyle modifications, intake of antioxidants, or treatment of infections and inflammation. Using various clinical scenarios Agarwal et al. have documented the various conditions in which SDF testing is required (5). For example, couples undergoing IVF/ ICSI with recurrent failure should undergo SDF testing. Moreover, men with advanced age, increased BMI, poor social habits like smoking, or with occupational exposure to endocrine disrupting chemicals or heavy metals are also candidates for SDF testing. In addition to men with clinical grade 2/3 varicocele who are considered candidates for varicocelectomy (5), Agarwal et al. advocate that men with grade 1 varicocele with normal or abnormal semen parameters but high SDF should undergo varicocelectomy as post-varicocelectomy there is a significant decline in DNA damage/SDF. It is noteworthy that the majority of factors which result in oxidative stress are modifiable like poor social habits, infection, psychological stress, intake of processed nutritionally depleted foods, sedentary lifestyle, and excessive use of cell phone (6). It is therefore important to collect a detailed social, occupational, dietary and lifestyle history of the patient undergoing infertility evaluation accompanied by a thorough clinical examination to provide appropriate therapeutics and counseling. By virtue of its high polyunsaturated fatty acid and limited cytosolic content and thus a highly deficient antioxidant capacity, and a highly truncated DNA damage detection and repair mechanism, sperm are most vulnerable to DNA damage and is dependent on the oocyte for complete removal of damaged DNA and oxidized DNA adducts. But aged oocyte with aberrant, inefficient, imperfect repair may result in persistence of DNA lesions and mutagenic DNA bases post fertilization (7). Persistence of mutagenic bases and dysregulated sperm transcripts Commentary