Spermatozoal sensitive biomarkers to defective protaminosis and fragmented DNA

Human sperm DNA damage may have adverse effects on reproductive outcome. Infertile men possess substantially more spermatozoa with damaged DNA compared to fertile donors. Although the extent of this abnormality is closely related to sperm function, the underlying etiology of ensuing male infertility is still largely controversial. Both intra-testicular and post-testicular events have been postulated and different mechanisms have been proposed to explain the presence of damaged DNA in human spermatozoa. Three among them, i.e. abnormal chromatin packaging, oxidative stress and apoptosis, are the most studied and discussed in the present review. Furthermore, results from numerous investigations are presented, including our own findings on these pathological conditions, as well as the techniques applied for their evaluation. The crucial points of each methodology on the successful detection of DNA damage and their validity on the appraisal of infertile patients are also discussed. Along with the conventional parameters examined in the standard semen analysis, evaluation of damaged sperm DNA seems to complement the investigation of factors affecting male fertility and may prove an efficient diagnostic tool in the prediction of pregnancy outcome. Background Sperm chromatin maturity and DNA integrity are necessary prerequisites for the completion of fertilization and subsequent embryo development [1]. Although an important level of sperm nuclear DNA damage can be detected in men with normal semen parameters, this is higher in infertile patients attending reproductive clinics and prominent among barely fertile older men [2]. Sperm DNA damage may be attributed to abnormal chromatin packaging, oxidative stress or poor DNA integrity [3]. Many studies combining standard semen analysis data with direct or indirect methods for the assessment of sperm DNA integrity and the evaluation of the DNA Fragmentation Index (DFI) from sperm used in ART, showed that there are threshold values of sperm DNA damage, beyond which embryo development and pregnancy outcome are severely compromised [4-12]. Furthermore, sperm DNA damage thresholds have been proposed in assays applied to in vivo conditions [4,5,13-15]. Thus, the clinician is guided as to the therapeutic approach that should be followed for the treatment of male infertility, according to the level of sperm chromatin maturity and DNA integrity found in the ejaculate [16]. Following a standard semen analysis, men are usually classified as infertile, sub-fertile or fertile and the World Health Organization (WHO) has suggested a range of arbitrary threshold values for human semen parameters, Published: 30 August 2007 Reproductive Biology and Endocrinology 2007, 5:36 doi:10.1186/1477-7827-5-36 Received: 26 May 2007 Accepted: 30 August 2007 This article is available from: http://www.rbej. com/content/5/1/36 © 2007 Angelopoulou et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.