Mechanisms and clinical correlates of sperm DNA damage

Abstract

Among the different DNA anomalies that can be present in the male gamete, DNA fragmentation is the most frequent, particularly in infertile subjects. There is now consistent evidence that a sperm containing fragmented DNA can be alive, motile, morphologically normal and able to fertilize an oocyte. There is also evidence that the oocyte is able to repair DNA damage; however, the extent of this repair depends on the type of DNA damage present in the sperm, as well as on the quality of the oocyte. Thus, it is important to understand the possible consequences of sperm DNA fragmentation (SDF) for embryo development, implantation, pregnancy outcome and the health of progeny conceived, both naturally and by assisted reproductive technology (ART). At present, data on the consequences of SDF for reproduction are scarce and, in many ways, inconsistent. The differences in study conclusions might result from the different methods used to detect SDF, the study design and the inclusion criteria. Consequently, it is difficult to decide whether SDF testing should be carried out in fertility assessment and ART. It is clear that there is an urgent need for the standardisation of the methods and for additional clinical studies on the impact of SDF on ART outcomes.

Figure 1

Assays used to evaluate sperm DNA fragmentation and measurement technologies that can be used. AOT, acridine orange test; COMET, single-cell gel electrophoresis assay; FC, flow cytometry; FM, fluorescence microscopy; ISNT, in situ nick translation; SCD, sperm chromatin dispersion test; SCSA, sperm chromatin structure assay; TUNEL, terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick-end labelling.