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The Effects of Virally‐Induced Maternal Inflammation on the Methylation Patterns of Skeletal Muscle in Offspring
Author(s) -
Hogan Elizabeth K.,
Beever Jonathan E.,
Dilger Anna C.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.979.2
Subject(s) - offspring , biology , dna methylation , methylation , epigenetics , cpg site , gene , andrology , bisulfite sequencing , genetics , gene expression , pregnancy , medicine
Porcine reproductive and respiratory syndrome virus (PRRSV) infection during gestation is associated with increased cytokine expression and reduced muscle fiber development in the offspring of infected sows. As maternal environment can potentially alter DNA methylation patterns of progeny during development, the influence of virally‐induced maternal inflammation on the methylome of skeletal muscle in piglets was investigated. We propose that the changes in immune function and muscle development observed in the offspring of PRRSV‐infected sows are the result of epigenetic modifications in the progeny's genome. More specifically, we suggest that changes in the methylation patterns of the offspring's genome are associated with genes belonging to pathways regulating muscle growth and immune response. Pregnant pigs were inoculated with either PRRSV or sterile culture medium (CON) on approximately day 80 of gestation. At birth, longissimus dorsi muscle samples were collected from uninfected male offspring. Reduced representation bisulfite sequencing was used to determine methylation status of individual CpG sites throughout the genome. Differentially methylated CpG sites, defined as having at least a 25% (q<0.01) difference in methylation between treatments, were used in pathway and gene ontology analyses. Overall frequency of methylated CpG sites was virtually unchanged between PRRSV (46.36% of CpG sites methylated) and CON offspring (46.30%). Despite this, methylation patterns differed between treatments with 5593 cytosines from 717 genes hypermethylated and 566 cytosines from 262 genes hypomethylated in PRRSV piglets compared with CON piglets. Several genes were extremely hypermethylated in PRRSV piglets, including FcγRII , MEF2C , citrate synthase, and PRKAB2 , and increased methylation was also observed in several disease response pathways, the thyroid hormone signaling pathway, and oxidative phosphorylation pathway. Differential methylation, mostly hypermethylation, was also present in genes for fast‐twitch myosin heavy chain isoforms, IGF1R , and several IGF binding proteins. Overall, these data suggest that differential methylation resulting from maternal infection and inflammation underlies reductions in offspring muscle development and growth.