title: Methylating micronutrient supplementation during pregnancy influences foetal hepatic gene expression and IGF signalling and increases foetal weight.
abstract: OBJECTIVE
  Maternal diet during pregnancy impacts foetal growth and development. In particular, dietary levels of methylating micronutrients (methionine, folate, choline, vitamins B6, and B12) interfere with the availability and allocation of methyl groups for methylation reactions, thereby influencing normal transcription. However, the currently recommended methylating micronutrient supplementation regimen is haphazard and arbitrary at best.
  
  
  METHODS
  To investigate the effects of a methylating micronutrient-rich maternal diet, pregnant Pietrain sows were fed either a standard diet (CON) or a diet supplemented with methionine, folate, choline, B6, B12, and zinc (MET). Foetal liver and muscle (M. longissimus dorsi) tissues were collected at 35, 63, and 91 days post-conception. Transcriptional responses to diet were assessed in foetal liver. Altered insulin-like growth factor (IGF) signalling in transcriptome analyses prompted investigation of IGF-2 and insulin-like growth factor binding proteins (IGFBPs) levels in muscle and liver.
  
  
  RESULTS
  Maternal diet enriched with methylating micronutrients was associated with increased foetal weight in late gestation. Hepatic transcriptional patterns also revealed differences in vitamin B6 and folate metabolism between the two diets, suggesting that supplementation was effective. Additionally, shifts in growth-supporting metabolic routes of the lipid and energy metabolism, including IGF signalling, and of cell cycle-related pathways were found to occur in liver tissue in supplemented individuals. Weight differences and modulated IGF pathways were also reflected in the muscle content of IGF-2 (increased in MET) and IGFBP-2 (decreased in MET).
  
  
  CONCLUSIONS
  Maternal dietary challenges provoke stage-dependent and tissue-specific transcriptomic modulations in the liver pointing to molecular routes contributing to the organismal adaptation. Subtle effects on late foetal growth are associated with changes in the IGF signalling mainly in skeletal muscle tissue that is less resilient to dietary stimuli than liver.
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196, Dummerstorf, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Oster
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196, Dummerstorf, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Nuchchanart
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196, Dummerstorf, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Trakooljul
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196, Dummerstorf, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Muráni
authors.affiliation: Department of Animal Nutrition, Martin-Luther-University Halle-Wittenberg, Theodor-Lieser-Str. 11, 06120, Halle (Saale), Germany.
authors.forename: A
authors.initials: A
authors.lastname: Zeyner
authors.affiliation: Ligandis GbR, Dorfstr. 14, 18276, Gülzow-Prüzen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Wirthgen
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196, Dummerstorf, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hoeflich
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196, Dummerstorf, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ponsuksili
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196, Dummerstorf, Germany. wimmers@fbn-dummerstorf.de.
authors.forename: K
authors.initials: K
authors.lastname: Wimmers
mesh_terms: D000821:Animal Feed / Q000032:analysis; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D002794:Choline / Q000008:administration & dosage; D004032:Diet / Q000662:veterinary; D019587:Dietary Supplements; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D020567:Fetal Weight / Q000187:drug effects*; D005333:Fetus / Q000187:drug effects; D005492:Folic Acid / Q000008:administration & dosage; D015870:Gene Expression; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena; D008715:Methionine / Q000008:administration & dosage; D018977:Micronutrients / Q000008:administration & dosage*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D015398:Signal Transduction; D013552:Swine; D014805:Vitamin B 12 / Q000008:administration & dosage; D025101:Vitamin B 6 / Q000008:administration & dosage
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D018977:Micronutrients; D007335:Insulin-Like Growth Factor II; D025101:Vitamin B 6; D005492:Folic Acid; D008715:Methionine; D002794:Choline; D014805:Vitamin B 12
keywords: Foetal programming; IGF system; Maternal diet; Methyl donors; One-carbon cycle; Pigs