In Utero Exposure to Benzo[ a ]Pyrene Increases Mutation Burden in the Soma and Sperm of Adult Mice

Autor:	Jason M. O'Brien, Marc A. Beal, Carole L. Yauk, Francesco Marchetti, Matthew J. Meier, Beverly Allan
Rok vydání:	2017
Předmět:	Male 0301 basic medicine Health Toxicology and Mutagenesis Cell Disease Biology medicine.disease_cause Andrology Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Benzo(a)pyrene medicine Animals Genetics Mutation Research Public Health Environmental and Occupational Health Spermatozoa Embryonic stem cell Sperm 3. Good health 030104 developmental biology medicine.anatomical_structure chemistry In utero Female Soma 030217 neurology & neurosurgery DNA Damage Mutagens
Zdroj:	Environmental Health Perspectives
ISSN:	1552-9924 0091-6765
DOI:	10.1289/ehp211
Popis:	Background: Mosaicism, the presence of genetically distinct cell populations within an organism, has emerged as an important contributor to disease. Mutational events occurring during embryonic development can cause mosaicism in any tissue, but the influence of environmental factors on levels of mosaicism is unclear. Objectives: We investigated whether in utero exposure to the widespread environmental mutagen benzo[a]pyrene (BaP) has an impact on the burden and distribution of mutations in adult mice. Methods: We used the Muta™Mouse transgenic rodent model to quantify and characterize mutations in the offspring of pregnant mice exposed to BaP during postconception days 7 through 16, covering the major period of organogenesis in mice. Next-generation DNA sequencing was then used to determine the spectrum of mutations induced in adult mice that were exposed to BaP during fetal development. Results: Mutation frequency was significantly increased in the bone marrow, liver, brain, and sperm of first filial generation (F1) males. Developing embryos accumulated more mutations and exhibited higher proportions of mosaicism than exposed adults, particularly in the brain. Decreased sperm count and motility revealed additional negative impacts on the reproductive function of F1 males. Conclusion: In utero exposure to environmental mutagens contributes to somatic and germline mosaicism, permanently affecting both the genetic health of the F1 and the population gene pool. Citation: Meier MJ, O’Brien JM, Beal MA, Allan B, Yauk CL, Marchetti F. 2017. In utero exposure to benzo[a]pyrene increases mutation burden in the soma and sperm of adult mice. Environ Health Perspect 125:82–88; http://dx.doi.org/10.1289/EHP211
Databáze:	OpenAIRE
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