Sperm chromatin integrity, DNA fragmentation and male fertility
Enciso M., Wells D.
During the last 15 years, largely as a result of the advent of assisted reproductive technology (ART), many research groups have focussed their attention on the study of sperm chromatin and its impact on reproductive outcome. Published studies on the topic have allowed for real progress in our understanding of elementary aspects of sperm chromatin structure and composition. Some have also shed some light on the impact of chromatin defects on sperm function and the ability to produce viable embryos. We are now beginning to understand how the sperm nucleus is configured and the implications of sperm genetic integrity on male fertility. As a result of the growing interest in this area, many novel tests to assess sperm chromatin composition and/or integrity have been developed. Currently available tests are directed to identify the presence of DNA and/or chromatin defects in the sperm nucleus, either by detecting DNA breaks or by assessing chromatin configuration in individual spermatozoa. A higher incidence of spermatozoa with chromatin defects has been found in samples from infertile subjects compared to those from fertile men, suggesting that sperm chromatin damage can be considered as a new biomarker of semen quality that may help in the identification and characterisation of men with fertility problems. Correlations between DNA damage in spermatozoa and adverse ART reproductive outcomes, such as reduced fertilization and conception rates, increased miscarriage and elevated incidence of birth defects have been described. It therefore seems that sperm genetic integrity is a requirement for successful fertilization and adequate embryo development. However, despite the advances made so far in the field of sperm chromatin integrity and male infertility, the clinical relevance of the data is still debated. More studies are needed in order to determine the specifics of sperm chromatin configuration and gain an improved understanding of the origin and implications of chromatin defects in spermatozoa. Many essential questions remain to be answered, further investigations on sperm chromatin structure, chromatin packaging and unpackaging during spermatogenesis and after fertilization, and the capacity of the oocyte to repair sperm DNA damage, are essential to have a better understanding of the genetic integrity of the male germ line and its significance on reproduction. This chapter reviews our present knowledge on the structure and composition of sperm chromatin, the existing information about the origin and aetiology of DNA damage in spermatozoa, the methods available for the analysis of sperm genetic integrity, and some of the most relevant clinical data produced over the last years about the correlations found between sperm chromatin defects and adverse reproductive outcomes. © 2012 by Nova Science Publishers, Inc. All rights reserved.