Disruption of maternal DNA repair increases sperm-derived chromosomal aberrations

• DOI: 10.1073/pnas.0705257104
• Publication Date: 2007-11-01T01:17:43Z
• Authors: F. Marchetti; J. Essers; R. Kanaar; A. J. Wyrobek
• Keywords: Male; Dna Damages; ionizing radiation DNA repair zygote chromosomal aberrations; DNA Repair; Genotype; Zygote; Mothers; Mice, Inbred Strains; Ionizing Radiation Dna Repair Zygote Chromosomalaberrations; Biological Pathways; Dna Repair; Mice; 03 medical and health sciences; Origin; Zygotes Ionizing Radiation Dna Repair Zygote Chromosomalaberrations; Pregnancy; Y Chromosome; Genetics; Animals; Children; Chromosome Aberrations; Recombination, Genetic; 0303 health sciences; Basic biological sciences; Models, Genetic; Males; 59; Dna; Spermatozoa; Chromosomal Aberrations; 3. Good health; EMC MM-03-32-04; Mice, Inbred C57BL; Germ Cells; Fertilization; EMC MGC-01-12-03; Female; Repair; Ionizing Radiations

Male and female germ cells can transmit genetic defects that lead to pregnancy loss, infant mortality, birth defects, and genetic diseases in offspring; however, the parental origins of transmitted defects are not random, with de novo mutations and chromosomal structural aberrations transmitted predominantly by sperm. We tested the hypotheses that paternal mutagenic exposure during late spermatogenesis can induce damage that persists in the fertilizing sperm and that the risk of embryos with paternally transmitted chromosomal aberrations depends on the efficiency of maternal DNA repair during the first cycle after fertilization. We show that female mice with defective DNA double-strand break repair had significantly increased frequencies of zygotes with sperm-derived chromosomal aberrations after matings with wild-type males irradiated 7 days earlier with 4 Gy of ionizing radiation. These findings demonstrate that mutagenic exposures during late spermatogenesis can induce damage that persists for at least 7 days in the fertilizing sperm and that maternal genotype plays a major role in determining the risks for pregnancy loss and frequencies of offspring with chromosomal defects of paternal origin.