Maternal Folic Acid Supplementation Induces Differential Changes in the Hepatic Transcriptome of Young Adult Male Progeny — ASN Events

Maternal Folic Acid Supplementation Induces Differential Changes in the Hepatic Transcriptome of Young Adult Male Progeny (#170)

Wing Hong Chu 1 , Lyn Harland 1 , Patricia Grant 1 , Miles De Blasio 1 , Wee-Ching Kong 1 , Simon Moretta 1 , Jeffery S Robinson 1 , Marie E Dziadek 2 , Julie A Owens 1
  1. Robinson Institute and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia
  2. Garvan Research Institute, Sydney, Australia

Maternal folic acid supplementation (MFAS) is promoted as a preventative measure against neural tube defects in the newborn. With folate known to participate in epigenetic processes such as the methylation of DNA and histones, which can regulate expression of coding genes and non-coding RNA genes, MFAS may have unforeseen consequences on the hepatic transcriptome of young adult male progeny, thus this aspect was examined.

Female Wistar rats were fed one of two diets: Control (n=8, 2mg folic acid/kg) or Folic Acid Supplemented (n=8, 6mg folic acid/kg), from two weeks before mating until delivery. Male offspring were weaned onto a standard chow diet, killed with their liver collected on postnatal day 90. Global transcriptional profiling was performed with Affymetrix Rat Gene 1.0ST Array. Data were normalised with RMA plugin, and analysed on BRB-Arraytools using class comparison. Canonical pathways and molecular networks modulated by the differentially expressed genes were identified with Ingenuity Pathway Analysis.

MFAS caused differential expression of twenty two genes in the liver of young adult male offspring, with 10 being upregulated (1.19 to 1.76 fold), including acyl-CoA synthetise medium-chain family member 3 (Acsm3), interleukin 17 receptor B (Il17rb); and 12 being down regulated (0.43 to 0.85), including aldo-keto reductase family 1, member B7(Akr1b7) . The upregulated genes were associated with a network in cellular growth and were enriched in seven canonical pathways including notch signalling. The downregulated genes were associated with three networks involved with cellular assembly and organisation, as well as six canonical pathways that participate in the metabolism of galactose, fructose, mannose and pyruvate.

Maternal folic acid supplementation alters hepatic expression of genes involved in carbohydrate and lipid metabolism and may affect their regulation in young adult male offspring, which may account for their reportedly improved lipidaemia and glucose tolerance.

  1. Chmurzynska, A., M. Stachowiak, et al. (2012). "Protein and folic acid content in the maternal diet determine lipid metabolism and response to high-fat feeding in rat progeny in an age-dependent manner." Genes Nutr 7(2): 223-234.