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.


METHODS
Experimental prospective study.


METHODS
Embryology research laboratory.


METHODS
Swiss albino mice.


METHODS
The sperm DNA damage was induced by different doses of gamma-irradiation to male mice followed by mating with healthy female mice.


METHODS
Genomic integrity in embryos, fetus, and spermatozoa of F1 mice derived from the DNA-damaged sperm.


RESULTS
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.


CONCLUSIONS
Sperm-mediated transgenerational genomic instability is dependent on the amount of DNA damage present in the sire's sperm at the time of fertilization.
Adiga
Satish Kumar
SK
Division of Reproductive Medicine, Kasturba Medical College, Manipal University, Manipal, India. satish.adiga@manipal.edu
Upadhya
Dinesh
D
Kalthur
Guruprasad
G
Bola Sadashiva
Satish Rao
SR
Kumar
Pratap
P
D000818:Animals; D001755:Blastocyst / Q000528:radiation effects; D004249:DNA Damage; D004622:Embryo, Mammalian / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays; D042822:Genomic Instability / Q000528:radiation effects*; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000528:radiation effects; D018812:Paternal Exposure; D011446:Prospective Studies; D013094:Spermatozoa / Q000528:radiation effects*