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Paternal Benzo[a]pyrene Exposure Modulates MicroRNA Expression Patterns in the Developing Mouse Embryo
Asgeir Brevik1, Birgitte Lindeman, Gunnar Brunborg
1Division of Environmental Medicine, Department of Chemical Toxicology, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, 0403 OSLO, Norway.
Abstract:
Little attention has been given to how microRNA expression is affected by environmental contaminants exposure. We investigate the effects of paternal exposure to benzo[a]pyrene (B[a]P) on miRNA expression in the developing mouse embryo. Male mice were exposed to B[a]P (150 mg/kg i.p.), and their sperm was used four days later in in-vitro fertilization experiments. Twenty embryos each from 2-, 8-cell and the blastocyst stage were used for genome-wide miRNA expression profiling. Paternal exposure to B[a]P affected the expression of several miRNAs, and the target genes for some of the dysregulated miRNAs were enriched in many different pathways that are likely to be relevant for the developing mouse embryo. By linking the miRNA target genes to publicly available databases, we identified some miRNA target genes that may serve as global markers of B[a]P-mediated genotoxic stress. The dysregulated miRNAs may provide valuable knowledge about potential transgenerational effects of sublethal exposure to chemicals.
Insights
Paternal exposure to the environmental contaminant benzo[a]pyrene (B[a]P) altered microRNA (miRNA) expression in developing mouse embryos. These changes in miRNA targets suggest potential transgenerational effects from chemical exposures.
Area of Science:
- Environmental toxicology
- Developmental biology
- Molecular genetics
Background:
- Environmental contaminants can impact reproductive health and offspring development.
- The role of microRNA (miRNA) dysregulation in response to chemical exposure is not well understood.
- Benzo[a]pyrene (B[a]P) is a common environmental pollutant with known toxic effects.
Purpose of the Study:
- To investigate the effects of paternal exposure to benzo[a]pyrene (B[a]P) on miRNA expression in mouse embryos.
- To identify specific miRNAs and their target genes affected by B[a]P exposure.
- To explore the potential for these changes to serve as biomarkers of B[a]P-induced genotoxic stress.
Main Methods:
- Male mice were exposed to B[a]P (150 mg/kg).
- Sperm from exposed mice were used for in vitro fertilization.
- Genome-wide miRNA expression profiling was performed on embryos at 2-cell, 8-cell, and blastocyst stages.
Main Results:
- Paternal B[a]P exposure significantly altered the expression of several miRNAs in developing embryos.
- Target genes of dysregulated miRNAs were enriched in pathways crucial for embryonic development.
- Specific miRNA target genes were identified as potential global markers of B[a]P-mediated genotoxic stress.
Conclusions:
- Paternal exposure to B[a]P induces miRNA expression changes in offspring embryos.
- Dysregulated miRNAs and their targets offer insights into the molecular mechanisms of B[a]P toxicity.
- These findings highlight potential transgenerational impacts of sublethal environmental chemical exposure.
