Epigenetic Regulation of Insulin-Like Growth Factor-1 by a Methyl Donor-rich Diet in a Transgenerational Model of Intrauterine Growth Restriction.

Dasso, Joseph F.; Hu, Min; Shope, Cindy; Showalter, Lori; Lane, Robert H.; Aagaard, Kjersti M.

doi:10.1093/biolreprod/85.s1.319

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“…In contrast, MET deficiency during pregnancy impaired fetal gastric ghrelin cell organization and decreased plasma ghrelin levels in rats [ 19 ]. Research has shown that dietary supplementation with MET altered the methylation of fibroblast growth factor 21 [ 20 ] and insulin-like growth factor-1 in fetal liver in an IUGR rat model [ 21 ]. A significant differential methylation was observed in the promoter region of H19 in the liver among the IUGR group participants, whereas the MET diet was associated with hypermethylation in the IUGR group rats [ 22 ].…”

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confidence: 99%

Effects of maternal methyl donor intake during pregnancy on ileum methylation and function in an intrauterine growth restriction pig model

Lin,

Wu,

Zhuo

et al. 2024

J Animal Sci Biotechnol

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Background Intrauterine growth retardation (IUGR) affects intestinal growth, morphology, and function, which leads to poor growth performance and high mortality. The present study explored whether maternal dietary methyl donor (MET) supplementation alleviates IUGR and enhances offspring’s growth performance by improving intestinal growth, function, and DNA methylation of the ileum in a porcine IUGR model. Methods Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery. After farrowing, 8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum. Results The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets. Moreover, maternal MET supplementation significantly reduced the plasma concentrations of isoleucine, cysteine, urea, and total amino acids in sows and newborn piglets. It also increased lactase and sucrase activity in the jejunum of newborn piglets. MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets. DNA methylation analysis of the ileum showed that MET supplementation increased the methylation level of DNA CpG sites in the ileum of newborn piglets. Down-regulated differentially methylated genes were enriched in folic acid binding, insulin receptor signaling pathway, and endothelial cell proliferation. In contrast, up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosynthetic process. Conclusions Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets, which may be associated with better intestinal function and methylation status.

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