Format

Send to

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17725-9. Epub 2007 Oct 31.

Disruption of maternal DNA repair increases sperm-derived chromosomal aberrations.

Author information

1
Biosciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA. fmarchetti@lbl.gov

Abstract

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.

PMID:
17978187
PMCID:
PMC2077046
DOI:
10.1073/pnas.0705257104
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center