Germline drift in chimeric male mice possessing an F2 component with a paternal F0 radiation history

Abstract

In earlier work using mouse chimeric embryos we have shown that pre-implantation embryonic cells with a history of paternal γ-irradiation (1 Gy) 6 weeks prior to conception demonstrated a competitive cell proliferation disadvantage when challenged by direct cell-cell contact with control pre-implantation embryos in chimeras even two generations after paternal irradiation. This effect on embryonic cell proliferation was associated with paternal irradiation of sensitive type A/B spermatogonia 6 weeks prior to conception but not from irradiation 5 weeks prior to conception. The purpose of this new study is to test the hypothesis that germ cell lines with a history of acute irradiation may also exhibit a selection disadvantage or germline chimeric drift over time in adult male mice two generations after paternal irradiation in chimeric mice. F0 male CD1 mice received a 1.0 Gy whole body absorbed dose of attenuated 137Cs γ-rays and were mated at post-irradiation weeks 5 and 6. Chimeric XY↔XY male CD1 mice were constructed with F2 embryos from the F1 offspring and with control embryos. To distinguish the control germline cells, the control embryos were heterozygous for the neo transgene, which served as a cell lineage marker. To test for germline chimeric drift, each XY↔XY chimera was mated periodically from age 7 to 21 weeks with a different CD1 female. The fraction of offspring from each liter with the neo marker was used to quantify the relative contribution of the control germ cell lineage to the fertilizing sperm population. The results showed that there was a significant selection against germ cells with the paternal F0 post-irradiation week 6 history. In contrast, there was a very small but significant selection in favor of the germ cells with the paternal F0 post-irradiation week 5 history. These results indicate that the effects of a relatively non-toxic dose of radiation (1 Gy) on cell proliferation transmitted by ancestral type B spermatogonia to the embryo are manifested in the germline of the adult male mice even after two generations.