Sperm DNA: organization, protection and vulnerability: from basic science to clinical applications--a position report

Abstract

This article reports the results of the most recent in a series of EHSRE workshops designed to synthesize the current state of the field in Andrology and provide recommendations for future work (for details see Appendix). Its focus is on methods for detecting sperm DNA damage and potential application of new knowledge about sperm chromatin organization, vulnerability and repair to improve the diagnosis and treatment of clinical infertility associated with that damage. Equally important is the use and reliability of these tests to identify the extent to which environmental contaminants or pharmaceutical agents may contribute to the incidence of sperm DNA damage and male fertility problems. A working group (for workshop details, see Appendix) under the auspices of ESHRE met in May 2009 to assess the current knowledgebase and suggest future basic and clinical research directions. This document presents a synthesis of the working group's understanding of the recent literature and collective discussions on the current state of knowledge of sperm chromatin structure and function during fertilization. It highlights the biological, assay and clinical uncertainties that require further research and ends with a series of 5 key recommendations.

Predictive value of DNA integrity analysis in idiopathic recurrent pregnancy loss following spontaneous conception

“…Among these, the excision repair pathways remove most of the physical damage to DNA as well as replication errors. However, mature spermatozoa being transcrptionally inert is not at par to repair the damage and the high proportion of embryo DNA damage are thought to be derived from male gamete [2]. Also, genetic polymorphisms of DNA repair genes (XRCC1, XPD6, XPD23) were significantly associated with high DFI [35].…”

Efficient combined FISH and PRINS technique for detection of DAZ microdeletion in human sperm

“…It was shown that there is variation in DAZ copy number in infertile men when using real time PCR [44] and that copy number variation affect total motile sperm count [45]. On the other hand there are reports showing DAZ gene is vulnerable to damage by environmental genotoxic agents such as ionizing radiation [23][24][25][26][27], and spermatozoa are particularly susceptible to ROS-induced damage due to presence of large quantities of polyunsaturated fatty acids and low concentrations of scavenging enzymes in their plasma membranes [46]. Also there are reports showing absence of DAZ genes in spermatozoa of infertile men with somatic DAZ deletions [32].…”

Meiotic recombination and male infertility: from basic science to clinical reality?

“…Perhaps some of the most exciting research in the field is from emerging studies that suggest that the process of spermatogenesis and fertilization is potentially mediated through a variety of other mechanisms that might be associated with infertility phenotypes, including: epigenetic modifications, 84,85 ubiquitination, 86,87 genome organization perturbations, 88 spermatozoal RNAs, 89 proteomics, 90 environmental contaminants and pharmacological agents that may contribute to sperm DNA damage 91 among others.…”