Abstract
The exposure of germ cells to radiation introduces mutations in the genomes of offspring, and a previous whole-genome sequencing study indicated that the irradiation of mouse sperm induces insertions/deletions (indels) and multisite mutations (clustered single nucleotide variants and indels). However, the current knowledge on the mutation spectra is limited, and the effects of radiation exposure on germ cells at stages other than the sperm stage remain unknown. Here, we performed whole-genome sequencing experiments to investigate the exposure of spermatogonia and mature oocytes. We compared de novo mutations in a total of 24 F1 mice conceived before and after the irradiation of their parents. The results indicated that radiation exposure, 4 Gy of gamma rays, induced 9.6 indels and 2.5 multisite mutations in spermatogonia and 4.7 indels and 3.1 multisite mutations in mature oocytes in the autosomal regions of each F1 individual. Notably, we found two types of deletions, namely, small deletions (mainly 1~12 nucleotides) in non-repeat sequences, many of which showed microhomology at the breakpoint junction, and single-nucleotide deletions in mononucleotide repeat sequences. The results suggest that these deletions and multisite mutations could be a typical signature of mutations induced by parental irradiation in mammals.
Highlights
The exposure of germ cells to radiation introduces mutations in the genomes of offspring, and a previous whole-genome sequencing study indicated that the irradiation of mouse sperm induces insertions/deletions and multisite mutations
It is known that 4 Gy of ionizing radiation (IR) exposure leads to a substantial reduction of mouse spermatogonial cells and it takes 10 weeks or more for the recovery of reproductive capacity[14], where it takes approximately 5 weeks for cells to develop from spermatogonia to sperm[8]
In the spermatogonia exposure experiment (Fig. 1a), a non-irradiated male C57BL/6J mouse was mated with a non-irradiated female C3H/HeN mouse to produce F1 mice, which served as controls
Summary
The exposure of germ cells to radiation introduces mutations in the genomes of offspring, and a previous whole-genome sequencing study indicated that the irradiation of mouse sperm induces insertions/deletions (indels) and multisite mutations (clustered single nucleotide variants and indels). Specific-locus tests in mice have suggested that the effects on mutation induction in offspring show variations among different parental exposures: male germ cells that have entered meiosis, as well as maturing and mature oocytes, show increased sensitivity to IR than spermatogonia[3,11]. These data suggest that it is important to understand the effects of IR on germ cells other than those at the sperm stage. We characterized and quantified the de novo mutations, mainly base substitutions and small indels, on spermatogonia and mature oocytes through WGS and consider the transgenerational effects of IR at the genome-wide level
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
