title: An obesogenic diet during mouse pregnancy modifies maternal nutrient partitioning and the fetal growth trajectory.
abstract: In developed societies, high-sugar and high-fat (HSHF) diets are now the norm and are increasing the rates of maternal obesity during pregnancy. In pregnant rodents, these diets lead to cardiovascular and metabolic dysfunction in their adult offspring, but the intrauterine mechanisms involved remain unknown. This study shows that, relative to standard chow, HSHF feeding throughout mouse pregnancy increases maternal adiposity (+30%, P<0.05) and reduces fetoplacental growth at d 16 (-10%, P<0.001). At d 19, however, HSHF diet group pup weight had normalized, despite the HSHF diet group placenta remaining small and morphologically compromised. This altered fetal growth trajectory was associated with enhanced placental glucose and amino acid transfer (+35%, P<0.001) and expression of their transporters (+40%, P<0.024). HSHF feeding also up-regulated placental expression of fatty acid transporter protein, metabolic signaling pathways (phosphoinositol 3-kinase and mitogen-activated protein kinase), and several growth regulatory imprinted genes (Igf2, Dlk1, Snrpn, Grb10, and H19) independently of changes in DNA methylation. Obesogenic diets during pregnancy, therefore, alter maternal nutrient partitioning, partly through changes in the placental phenotype, which helps to meet fetal nutrient demands for growth near term. However, by altering provision of specific nutrients, dietary-induced placental adaptations have important roles in programming development with health implications for the offspring in later life.
authors.affiliation: 1Centre for Trophoblast Research, Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, UK CB2 3EG. ans48@cam.ac.uk.
authors.forename: Amanda N
authors.initials: AN
authors.lastname: Sferruzzi-Perri
authors.forename: Owen R
authors.initials: OR
authors.lastname: Vaughan
authors.forename: Maria
authors.initials: M
authors.lastname: Haro
authors.forename: Wendy N
authors.initials: WN
authors.lastname: Cooper
authors.forename: Barbara
authors.initials: B
authors.lastname: Musial
authors.forename: Marika
authors.initials: M
authors.lastname: Charalambous
authors.forename: Diogo
authors.initials: D
authors.lastname: Pestana
authors.forename: Shruti
authors.initials: S
authors.lastname: Ayyar
authors.forename: Anne C
authors.initials: AC
authors.lastname: Ferguson-Smith
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Burton
authors.forename: Miguel
authors.initials: M
authors.lastname: Constancia
authors.forename: Abigail L
authors.initials: AL
authors.lastname: Fowden
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy
chemical_list: D004041:Dietary Fats
keywords: developmental programming; imprintome; metabolic signaling pathways; placental phenotype; resource allocation