Class
Article
College
College of Agriculture and Applied Sciences
Department
Animal, Dairy, and Veterinary Sciences Department
Faculty Mentor
Abby Benninghoff
Presentation Type
Oral Presentation
Abstract
A Western type dietary pattern is a major risk factor for colitis-associated colorectal cancer (CAC). Observations from transgenerational studies suggest that epimutations may be inherited, resulting in persistent aberrant gene expression in offspring. Previously, our group reported that ancestral exposure to the total Western diet (TWD) increased CAC incidence and disease severity in F3 offspring. Moreover, exposure to TWD over multiple generations exacerbated disease in F3 offspring as compared to those fed TWD directly. For the present work, we hypothesized that ancestral or cumulative exposure to TWD will result in differential expression of cancer critical genes, explains the greater tumor abundance and burden observed in these mice. C57BL/6J mice were bred for three generations, during which they were fed a standard control diet (AIN93G) for all generations or TWD during only the F0 generation (ancestral), the F0 through F3 generations (multi-generation), or only the F3 generation (direct). The azoxymethane and dextran sodium sulfate (AOM+DSS) model of CAC was employed in F3 offspring, from which colon mucosa RNA was isolated and used for Illumina RNAseq with EdgeR for differential expression analysis. About 700 to 4500 differentially expressed genes (DEGs) were identified in colon mucosa from AOM&DSS initiated offspring, as compared to sham controls. For initiated mice, 119 DEGs were identified comparing cumulative TWD exposure to controls, and 36 differed from direct TWD fed animals. In sham mice, 101 DEGs were identified comparing direct to cumulative TWD exposed offspring; interestingly, these DEGs were associated with defense response, immune response, and response to interferon biological process ontology terms. Exposure to the TWD over multiple generations caused significant changes in genes involved in immune response in third generation offspring. Assessment of genome-wide patterns of promoter methylation is near completion and expected to reveal an epigenetic mechanism of action.
Location
Room 155
Start Date
4-11-2019 1:30 PM
End Date
4-11-2019 2:45 PM
Included in
Impact of the Total Western Diet for Rodents on Colon Mucosal Gene Expression in a Multigenerational Murine Model of Colitis-Associated Colorectal Cancer
Room 155
A Western type dietary pattern is a major risk factor for colitis-associated colorectal cancer (CAC). Observations from transgenerational studies suggest that epimutations may be inherited, resulting in persistent aberrant gene expression in offspring. Previously, our group reported that ancestral exposure to the total Western diet (TWD) increased CAC incidence and disease severity in F3 offspring. Moreover, exposure to TWD over multiple generations exacerbated disease in F3 offspring as compared to those fed TWD directly. For the present work, we hypothesized that ancestral or cumulative exposure to TWD will result in differential expression of cancer critical genes, explains the greater tumor abundance and burden observed in these mice. C57BL/6J mice were bred for three generations, during which they were fed a standard control diet (AIN93G) for all generations or TWD during only the F0 generation (ancestral), the F0 through F3 generations (multi-generation), or only the F3 generation (direct). The azoxymethane and dextran sodium sulfate (AOM+DSS) model of CAC was employed in F3 offspring, from which colon mucosa RNA was isolated and used for Illumina RNAseq with EdgeR for differential expression analysis. About 700 to 4500 differentially expressed genes (DEGs) were identified in colon mucosa from AOM&DSS initiated offspring, as compared to sham controls. For initiated mice, 119 DEGs were identified comparing cumulative TWD exposure to controls, and 36 differed from direct TWD fed animals. In sham mice, 101 DEGs were identified comparing direct to cumulative TWD exposed offspring; interestingly, these DEGs were associated with defense response, immune response, and response to interferon biological process ontology terms. Exposure to the TWD over multiple generations caused significant changes in genes involved in immune response in third generation offspring. Assessment of genome-wide patterns of promoter methylation is near completion and expected to reveal an epigenetic mechanism of action.