Abstract

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This study examines how middle aged mice have varied stress responses by sex focusing on molecular processes driving differential response. 30 CB6/BALBc F1 mice were subjected to controlled stress through a laparotomy. We hypothesize that molecular analysis of these tissues can identify candidate molecules that drive sex-specific differential responses to stress. First, mice tissues were previously prepared and will be used in future, separate projects besides this one. Differential expression analysis showed 237 and 340 unique differentially expressed genes when comparing surgical to control subjects, for females and males respectively. Gene set enrichment analysis was used to identify pathways affected by differentially expressed genes, highlighted by downregulation of a variety of inflammatory, metabolic, and epigenetic pathways. Two genes of interest are saa1 and saa2 which are both downregulated in the female samples, but not in males. Other genes of interest for the males include Slc1a, Atg16l2, Aldh1b1 all of which are considerably downregulated. Protein expression by Western blot was performed using antibodies against gstm1 and saa1/2 due to their sex specific downregulation in males and females respectively. An antibody against phosphorylated STAT3 was used because it is upstream of many differentially expressed genes. While no statistically significant difference was found, trending results in expression for gstm1 and pSTAT3 indicate promising results for follow up experiments. Taken together, this broad molecular analysis revealed significant sex-specific gene expression and pathway enrichment in the liver, as well as interesting results to further investigate at the protein level in distant organs.