DNA Methylation of Genes Participating in Hepatic Metabolisms and Function in Fetal Calf Liver Is Altered by Maternal Undernutrition during Gestation
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Published:2023-06-26
Issue:13
Volume:24
Page:10682
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Muroya Susumu1ORCID, Otomaru Konosuke2, Oshima Kazunaga3, Oshima Ichiro4, Ojima Koichi1, Gotoh Takafumi5ORCID
Affiliation:
1. Division of Animal Products Research, NARO Institute of Livestock and Grassland Science (NILGS), Tsukuba 305-0901, Ibaraki, Japan 2. Joint Faculty of Veterinary Medicine, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-8580, Kagoshima, Japan 3. Division of Year-Round Grazing Research, NARO Western Region Agricultural Research Center, 60 Yoshinaga, Ohda 694-0013, Shimane, Japan 4. Department of Agricultural Sciences and Natural Resources, Kagoshima University, Korimoto 1-21-24, Kagoshima 890-8580, Kagoshima, Japan 5. Field Science Center for Northern Biosphere, Hokkaido University, N11W10, Kita, Sapporo 060-0811, Hokkaido, Japan
Abstract
This study aimed to elucidate the effects of maternal undernutrition (MUN) on epigenetic modification of hepatic genes in Japanese Black fetal calves during gestation. Using a previously established experimental design feeding the dams with 60% (LN) or 120% (HN) of their global nutritional requirements during the 8.5-month gestational period, DNA methylation in the fetal liver was analyzed with reduced representation bisulfite sequencing (RRBS). The promoters and gene bodies in the LN fetuses were hypomethylated compared to HN fetuses. Pathway analysis showed that the genes with DMR in the exon/intron in the LN group were associated with pathways involved in Cushing syndrome, gastric acid secretion, and aldosterone synthesis and secretion. Promoter hypomethylation in the LN group was frequently observed in genes participating in various signaling pathways (thyroid hormone, Ras/Rap1, PIK3-Akt, cAMP), fatty acid metabolism, and cholesterol metabolism. The promoter hypomethylated genes ALPL and GNAS were upregulated in the LN group, whereas the promoter hypermethylated genes GRB10 and POR were downregulated. The intron/exon hypomethylated genes IGF2, IGF2R, ACAD8, TAT, RARB, PINK1, and SOAT2 were downregulated, whereas the hypermethylated genes IGF2BP2, NOS3, and NR2F1 were upregulated. Collectively, MUN alters the promoter and gene body methylation of genes associated with hepatic metabolisms (energy, cholesterol, mitochondria) and function, suggesting an impact of altered gene methylation on the dysregulation of gene expression in the fetal liver.
Funder
Japan Society for the Promotion of Science the Canon Fund Livestock Promotional Subsidy of the Japan Racing Association Leave a Nest Co., Ltd.
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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