DNA repair efficiency in germ cells and early mouse embryos and consequences for radiation-induced transgenerational genomic damage
Exposure to ionizing radiation and other environmental agents can affect the genomic integrity of germ cells and induce adverse health effects in the progeny. Efficient DNA repair during gametogenesis and the early embryonic cycles after fertilization is critical for preventing transmission of DNA damage to the progeny and relies on maternal factors stored in the egg before fertilization. The ability of the maternal repair machinery to repair DNA damage in both parental genomes in the fertilizing egg is especially crucial for the fertilizing male genome that has not experienced a DNA repair-competent cellular environment for several weeks prior to fertilization. During the DNA repair-deficient period of spermatogenesis, DNA lesions may accumulate in sperm and be carried into the egg where, if not properly repaired, could result in the formation of heritable chromosomal aberrations or mutations and associated birth defects. Studies with female mice deficient in specific DNA repair genes have shown that: (i) cell cycle checkpoints are activated in the fertilized egg by DNA damage carried by the sperm; and (ii) the maternal genotype plays a major role in determining the efficiency of repairing genomic lesions in the fertilizing sperm and directly affect the risk for abnormal reproductive outcomes. There is also growing evidence that implicates DNA damage carried by the fertilizing gamete as a mediator of postfertilization processes that contribute to genomic instability in subsequent generations. Transgenerational genomic instability most likely involves epigenetic mechanisms or error-prone DNA repair processes in the early embryo. Maternal and embryonic DNA repair processes during the early phases of mammalian embryonic development can have far reaching consequences for the genomic integrity and health of subsequent generations.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- Life Sciences Division
- DOE Contract Number:
- DE-AC02-05CH11231
- OSTI ID:
- 961527
- Report Number(s):
- LBNL-1958E; TRN: US201012%%1579
- Resource Relation:
- Conference: International Symposium on Carcinogenesis and Genetic Effects of Low Dose Radiation, Rokkasho, Aomori, Japan, October 7-8, 2008
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CARCINOGENESIS
CELL CYCLE
CHROMOSOMAL ABERRATIONS
DAMAGE
DEFECTS
DNA
DNA DAMAGES
DNA REPAIR
DOSES
EFFICIENCY
EGGS
EMBRYOS
FEMALES
FERTILIZATION
GAMETES
GAMETOGENESIS
GENES
GENETIC EFFECTS
GENOTYPE
GERM CELLS
IONIZING RADIATIONS
MALES
MICE
MUTATIONS
ONTOGENESIS
PARTURITION
RADIATIONS
REPAIR
SPERMATOGENESIS
SPERMATOZOA
TRANSMISSION
sperm
oocyte
zygote
chromosomal damage