Evaluation of mutagenic susceptibility of different stages in germ cell development of Caenorhabditis elegans using whole genome sequencing

• Published in: Archives of toxicology 2023-08, Vol.97 (8), p.2261-2272
• Main Authors: Du, Hua, Pan, Bohu, Alund, Alexander W., Yan, Jian, Chen, Ying, Robison, Timothy W., Chen, Tao
• Format: Article
• Language: English
• Subjects: Alkylation; alkylation agents; Animals; Biomedical and Life Sciences; Biomedicine; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans Proteins - genetics; Developmental stages; Environmental Health; Ethyl methanesulfonate; Ethyl nitrosourea; Female; Females; Frequency analysis; Gene sequencing; Genetic disorders; genome; Genomes; Genotoxicity and Carcinogenicity; Germ cells; Germ Cells - metabolism; Hermaphroditism; Male; Males; Mitosis; Mutagens; Mutagens - toxicity; Mutation; mutation rate; Mutation rates; N-ethyl-N-nitrosourea; Nematodes; Next-generation sequencing; Occupational Medicine/Industrial Medicine; Offspring; Oogenesis; Pharmacology/Toxicology; progeny; Semen; Sensitivity analysis; Spermatogenesis; Spermatogenesis - genetics; spermatozoa; spontaneous mutation; Whole Genome Sequencing
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-023-03526-z

In contrast to somatic mutations, mutations in germ cells affect every cell of any organism derived from the germ cell and therefore are related to numerous genetic diseases. However, there is no suitable assay to evaluate the mutagenic sensitivities of both male and female germ cells. The main type of Caenorhabditis elegans ( C. elegans ) is hermaphroditic, where spermatogenesis and oogenesis occur chronologically at specific stages, allowing induction of mutations in either sperm or eggs exclusively. In this study, we used the alkylating agent ethyl methanesulfonate and N -ethyl- N -nitrosourea to induce germline mutations in C. elegans at different developmental stages and analyzed mutation frequency and mutational spectrum from data gathered using next-generation sequencing (NGS) technology. Our results revealed low spontaneous mutation rates of C. elegans , along with distinct mutagenic effects elicited by the two mutagens. Our data show that the parental worms treated during germ cell mitosis, spermatogenesis, and oogenesis resulted in different mutation frequencies in their offspring, and female germ cells could be very susceptible to mutagen exposure during oogenesis. In summary, our study indicates that the use of C. elegans and its specific chronological hermaphroditism would be a promising way to explore the sensitivities of both male and female germ cells to mutagens.