title: Intrauterine growth restriction affects the maturation of myelin.
abstract: Intrauterine growth-restriction (IUGR) can lead to adverse neurodevelopmental sequelae in postnatal life. Our objective was to determine whether IUGR, induced by chronic placental insufficiency (CPI) in the guinea pig results in long-term deficits in brain myelination and could therefore contribute to altered neural function. CPI was induced by unilateral ligation of the uterine artery at mid-gestation (term~67 days of gestation; dg), producing growth-restricted (GR) foetuses (60 dg), neonates (1 week) and young adults (8 week); controls were from the unligated horn or sham-operated animals. In GR foetuses (n=8) and neonates (n=7), white matter (WM) volume was reduced (p<0.05); this reduction did not persist in young adults (n=11) however the corpus callosum width was reduced (p<0.05). Immunoreactivity (IR) for myelin basic protein (MBP), myelin-associated glycoprotein (MAG) and myelin proteolipid protein (PLP), all markers of myelinating oligodendrocytes (OL), was reduced in GR foetuses compared to controls. MBP was the most markedly affected with an abnormal retention of protein in the OL soma and a reduction of its incorporation into the myelin sheath. MAG-IR OL density was reduced (p<0.05), while the density of OLs immunoreactive for Olig-2, a transcription factor expressed throughout the entire OL lineage, was increased (p<0.05). MBP-, MAG- and PLP-IR recovered to control levels postnatally. These results suggest that IUGR transiently delays OL maturation and myelination in utero but that myelination and WM volume are restored to control levels postnatally. Long-term deficits in myelination are therefore unlikely to be the major factor underlying the altered neurological function which can be associated with IUGR.
authors.affiliation: Department of Anatomy and Cell Biology, The University of Melbourne, Grattan Street, Parkville, Victoria, 3010, Australia. mary.tolcos@monash.edu
authors.forename: Mary
authors.initials: M
authors.lastname: Tolcos
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bateman
authors.forename: Rachael
authors.initials: R
authors.lastname: O'Dowd
authors.forename: Rachel
authors.initials: R
authors.lastname: Markwick
authors.forename: Krijn
authors.initials: K
authors.lastname: Vrijsen
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rehn
authors.forename: Sandra
authors.initials: S
authors.lastname: Rees
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D002585:Cesarean Section; D005260:Female; D047109:Fetal Development; D006168:Guinea Pigs; D008026:Ligation; D004676:Myelin Basic Protein / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D010927:Placental Insufficiency / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy; D055988:Uterine Artery / Q000601:surgery
chemical_list: D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein