Value of DNA integrity assays for fertility evaluation.
DNA damage in the male germ line is associated with failed fertilisation, impaired preimplantation development and poor pregnancy outcomes, whether the insemination is natural or artificial. It is also apparent that DNA damage in spermatozoa is associated with adverse impacts on the health and wellbeing of children. This may be particularly important in the case of conceptions involving intracytoplasmic sperm injection. With this technique DNA damaged spermatozoa that would, under physiological circumstances, be excluded from the conception process are able to initiate pregnancies. Although the oocyte actively repairs the DNA damage brought into the zygote by the fertilising spermatozoon, errors in this repair process would generate mutations that might in turn be linked to the increased incidence of dominant genetic disease and childhood cancer seen in the offspring of fathers possessing DNA damaged spermatozoa. Significantly, the incidence of such mutations is so low that it might be several generations before the full consequences of using DNA damaged spermatozoa in assisted conception cycles are realised. The factors modulating DNA damage in the male germ line are complex and largely unresolved. They involve advanced paternal age, exposure to xenobiotics and male genital tract infection. The types of damage being measured by the assays used in most laboratories (SCSA, Comet and TUNEL) are also uncertain. Molecular characterization of this DNA damage might provide insights into the underlying aetiologies, facilitate the development of optimised diagnostic methods for its detection and suggest logical avenues to pursue for its correction and ultimate prevention.
Aitken
R John
RJ
ARC Centre of Excellence in Biotechnology and Development and Discipline of Biological Sciences, University of Newcastle, NSW 2308, Australia. jaitken@mail.newcastle.edu.au
De Iuliis
Geoffry N
GN
D000130:Achondroplasia / Q000235:genetics; D000328:Adult; D020552:Comet Assay; D004249:DNA Damage; D006801:Humans; D020287:In Situ Nick-End Labeling; D007248:Infertility, Male / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D010331:Paternal Age; D012728:Sex Chromatin / Q000648:ultrastructure; D020554:Sperm Injections, Intracytoplasmic; D013094:Spermatozoa / Q000648:ultrastructure*