The effects of maternal irradiation on ESTR mutation induction and transgenerational instability in mice

The main source of data used to assess genetic risks of radiation exposure for humans has been derived from experiments analysing the male germline, while the effects of maternal irradiation remain poorly understood. This project therefore aims to analyse the long term genetic effects of acute maternal irradiation. To investigate the effects of acute irradiation on genome stability in the germline of directly exposed females, adult BALB/c and CBA/Ca mice were exposed to 1 Gy of acute X-rays and mated with control males 2-5 days following exposure, enabling analyses of offspring that were conceived from irradiated dictyate oocytes in maturing follicles. The data revealed that frequency of mutation at expanded simple tandem repeat (ESTR) loci in the germline of directly exposed females did not differ from that in control families. To address the effect of parental irradiation on transgenerational instability, ESTR mutation frequency was also established in the germline and somatic tissues of first-generation offspring of exposed adult males and females using single-molecule PCR. The breeding scheme used implied that the offspring of irradiated males and females were derived from irradiated post-meiotic stages spermatozoa and meiotically arrested dictyate oocytes in maturing follicles, respectively. While the frequency ESTR mutation in the offspring of irradiated males was significantly elevated, maternal irradiation did not affect the F1 stability. The results of this project therefore show that, in sharp contrast to the paternal exposure to ionising radiation, the transgenerational effects of maternal high-dose acute irradiation are likely to be negligible. The analysis of transcription profiles of first-generation offspring of irradiated males and females reveals drastically different patterns of gene expression profiles in both groups. Specifically, a substantial number of genes significantly deregulated in the offspring of irradiated males belong to functional groups directly involved in maintaining the stability of the genome. In contrast, in the offspring of irradiated females none of the significantly deregulated genes can be implicated in the maintenance of genome stability. The work presented here therefore provide new evidence for striking differences in the manifestation of long-term effects of paternal and maternal acute exposure to ionising radiation in mice.