Effects of DNA methylation and gene expression on rats with protein malnutrition in early life

Although the mechanisms underlying how malnutrition in early life affects the susceptibility to diseases later in life remain unclear, there is considerable interest in the potential role of DNA methylation in the intrauterine programming of diseases. In this study, digital gene expression profiles were used to analyze changes in gene expression of protein-restricted rats early in life, while intergenerational rat models were used to explore differences in whole blood genomic DNA methylation in an environment stimulated by maternal protein intervention. Nine rats were randomly divided into early-life low-protein group (LPE), fetal low-protein group (LPF), and normal control group (CON). The LPE group was fed a low-protein diet on the 1st day of pregnancy until the end of lactation. The LPF group was given low-protein diet during pregnancy. The CON group was given a 20% protein diet from the 1st day of pregnancy. Total mRNA was extracted from the sacrificed rats at the 48th week. The number of differentially expressed genes for LPE versus CON, LPF versus CON, and LPF versus LPE was 178, 223, and 302, respectively. Comparing LPE versus CON and LPF versus CON, the upregulated genes common to the two groups were Gimap-9, Serinc-4, Dnah-2, Sf3b-5, and Sat-2, and the downregulated genes were Ppp1r-3. Comparing LPF versus CON and LPF versus LPE, the upregulated genes were Mgat2 and Cars, and the downregulated genes were Ddx28 and Slc12a9. The differentially expressed genes were mainly related to cell metabolism, immune response, signaling pathway, endocrine metabolism, stress response, ATP binding, and other functions. Early-life protein malnutrition affects gene expression of rat offspring and involves multiple aspects of growth and development, with different stages of early-life malnutrition leading to altered DNA methylation expression of corresponding genes, mainly in mitochondrial genes.