Genome-wide DNA methylation analysis in jejunum of Sus scrofa with intrauterine growth restriction

Abstract

Intrauterine growth restriction (IUGR) may elicit a series of postnatal body developmental and metabolic diseases due to their impaired growth and development in the mammalian embryo/fetus during pregnancy. In the present study, we hypothesized that IUGR may lead to abnormally regulated DNA methylation in the intestine, causing intestinal dysfunctions. We applied reduced representation bisulfite sequencing (RRBS) technology to study the jejunum tissues from four newborn IUGR piglets and their normal body weight (NBW) littermates. The results revealed extensively regional DNA methylation changes between IUGR/NBW pairs from different gilts, affecting dozens of genes. Hiseq-based bisulfite sequencing PCR (Hiseq-BSP) was used for validations of 19 genes with epigenetic abnormality, confirming three genes (AIFM1, MTMR1, and TWIST2) in extra samples. Furthermore, integrated analysis of these 19 genes with proteome data indicated that there were three main genes (BCAP31, IRAK1, and AIFM1) interacting with important immunity- or metabolism-related proteins, which could explain the potential intestinal dysfunctions of IUGR piglets. We conclude that IUGR can lead to disparate DNA methylation in the intestine and these changes may affect several important biological processes such as cell apoptosis, cell differentiation, and immunity, which provides more clues linking IUGR and its long-term complications.Electronic supplementary materialThe online version of this article (10.1007/s00438-018-1422-9) contains supplementary material, which is available to authorized users.

Original low birth weight deteriorates the hindgut epithelial barrier function in pigs at the growing stage

“…Previous studies showed that the intestinal permeability of LBW piglets was nearly twice as high as that of normal piglets, suggesting impaired intestinal epithelial barrier function (23). A subsequent study found that LBW-induced changes in methylation in the intestine were mainly involved in biological processes, such as cell apoptosis and cell differentiation, suggesting that LBW piglets have a higher incidence of intestinal dysfunction (24). The adverse effects of LBW on fetuses and newborns may persist throughout the life cycle (25,26).…”

Birthweight determines intestinal microvasculature development and alters endothelial nitric oxide synthase density in young piglets

“…However, our results demonstrate a significantly less dense microvasculature in LBW when compared to NBW piglets, the latter showing 85% more endothelial mass per unit of intestinal tissue than LBW. Due to the implications of microcirculation on intestinal health, nutrient transportation and intestinal permeability (Cummins & Crean, 2017), we could speculate that its deficiency contributes to the lesser growth and feed efficiency, to the increased morbidity and to incidence of intestinal underdevelopment, observed in LBW piglets (Dong et al, 2014;Hu et al, 2018;Mickiewicz et al, 2012;Wang et al, 2015;Wu, Bazer, Wallace, & Spencer, 2006). However, it is noteworthy that the vWF-positive area is similar in both birthweight categories at birth and becomes larger in 3-day old NBW piglets.…”

DNA methylation as a regulator of intestinal gene expression

“…Notably, most genes that are differentially expressed at the transcriptional level between the suckling and weaning periods stabilize expression levels after weaning, suggesting that early life transitional states can influence gene expression in adult intestines (46) . Intra uterine growth restriction can also cause DNA methylation abnormalities (52) , which could contribute to the gastrointestinal dysfunctions presented by infants with very low birth weight.…”