Transgenerational changes in somatic and germ line genetic integrity of first-generation offspring derived from the DNA damaged sperm.

OBJECTIVE To report a more quantitative approach to study the influence of varying levels of sperm DNA damage on transgenerational changes in genomic instability in a mouse model. DESIGN Experimental prospective study. SETTING Embryology research laboratory. ANIMAL(S) Swiss albino mice. INTERVENTION(S) The sperm DNA damage was induced by different doses of gamma-irradiation to male mice followed by mating with healthy female mice. MAIN OUTCOME MEASURE(S) Genomic integrity in embryos, fetus, and spermatozoa of F1 mice derived from the DNA-damaged sperm. RESULT(S) The transgenerational changes in genetic integrity were attributed by a dose-dependent increase in the frequency of micronuclei in preimplantation embryos and a concomitant increase in genomic instability in fetal liver cells and sperm chromatin modifications in F1 males. A strong positive correlation was observed between the extent of sperm DNA damage and somatic and germ-line genomic instability. CONCLUSION(S) Sperm-mediated transgenerational genomic instability is dependent on the amount of DNA damage present in the sire's sperm at the time of fertilization.