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. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.