title: Dietary betaine supplementation to gestational sows enhances hippocampal IGF2 expression in newborn piglets with modified DNA methylation of the differentially methylated regions.
abstract: OBJECTIVE
  The adequate supply of methyl donors is critical for the normal development of brain. The purpose of the present study was to investigate the effects of maternal betaine supplementation on hippocampal gene expression in neonatal piglets and to explore the possible mechanisms.
  
  
  METHODS
  Gestational sows were fed control or betaine-supplemented (3 g/kg) diets throughout the pregnancy. Immediately after birth, male piglets were killed, and the hippocampus was dissected for analyses. The mRNA abundance was determined by reverse transcription real-time polymerase chain reaction. Protein content was measured by Western blot, and DNA methylation was detected by methylated DNA immunoprecipitation assay.
  
  
  RESULTS
  Prenatal betaine supplementation did not alter the body weight or the hippocampus weight, but increased the hippocampal DNA content as well as the mRNA expression of proliferation-related genes. Prenatal betaine supplementation increased serum level of methionine (P < 0.05) and up-regulated (P < 0.05) the mRNA and protein expression of betaine-homocysteine methyltransferase, glycine N-methyltransferase and DNA methyltransferase 1 in the neonatal hippocampus. Hippocampal expression of insulin growth factor II (IGF2) and its receptors IGF1R and IGF2R were all significantly up-regulated (P < 0.05) in betaine-treated group, together with a significant activation (P < 0.01) of the downstream extracellular signal-regulated kinase 1/2. Moreover, the differentially methylated region (DMR) 1 and 2 on IGF2 locus was found to be hypermethylated (P < 0.05) in the hippocampus of betaine-treated piglets.
  
  
  CONCLUSIONS
  These results indicate that maternal betaine supplementation enhances betaine/methionine metabolism and DNA methyltransferase expression, causes hypermethylation of DMR on IGF2 gene, which was associated with augmented expression of IGF2 and cell proliferation/anti-apoptotic markers in the hippocampus of neonatal piglets.
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
authors.forename: Qinwei
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
authors.forename: Xian
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
authors.forename: Demin
authors.initials: D
authors.lastname: Cai
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
authors.forename: Shiyan
authors.initials: S
authors.lastname: Sui
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
authors.forename: Haogang
authors.initials: H
authors.lastname: Song
authors.affiliation: Key Laboratory of Animal Physiology and Biochemistry, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China. zhao.ruqian@gmail.com.
authors.forename: Ruqian
authors.initials: R
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000097:blood; D001622:Betaine / Q000008:administration & dosage* / Q000097:blood; D019175:DNA Methylation / Q000187:drug effects*; D019587:Dietary Supplements; D005260:Female; D015870:Gene Expression; D056426:Genetic Loci; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D008715:Methionine / Q000097:blood; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013552:Swine
chemical_list: D012333:RNA, Messenger; D001622:Betaine; D007335:Insulin-Like Growth Factor II; D008715:Methionine; D048052:Mitogen-Activated Protein Kinase 3
keywords: Betaine; Cell proliferation; DNA methylation; Hippocampus; IGF2; Piglets