title: Recapitulation of characteristics of human placental vascular insufficiency in a novel mouse model.
abstract: OBJECTIVE
  We tested the effects of selective reduction of placental blood flow by mesenteric uterine artery branch ligation (MUAL) resulting in fetal growth restriction (FGR).
  
  
  METHODS
  Timed mated C57BL/6J Day(D) 18 dams were divided into two groups: MUAL (n = 18); and control-sham (n = 18). Pups were delivered on D20, cross-fostered to surrogate CD-1 mothers for 4 weeks, and followed for 8 weeks. Outcome data included birth and placental weight, postnatal growth, placental volume determined by stereology, quantification of placental insulin-like growth factors-1(IGF-1) and IGF-2 and IGF binding proteins(IGFBP 2 and 6) by ELISA and gene expression by qPCR and GeneChip microarray analysis.
  
  
  RESULTS
  Compared with control, MUAL had an 11% reduction in mean birth weight (1.06 ± 0.13 g vs. 0.94 ± 0.13 g, p < 0.001) but no difference in placental weight. At 4 weeks of age, mean body weights of MUAL pups were significantly lower than sham. By 8 weeks, males but not females MUAL mice achieved equivalent mean body weight to control. Placental labyrinth depth, volume, and placental gene expression of IGF-1 and 2 were significantly reduced by MUAL. In contrast, placental protein level of IGFBP-2 and 6 were significantly elevated in the MUAL. Genomic expression analysis demonstrated that MUAL pups significantly up-regulated genes that were associated with apoptosis and growth pathways.
  
  
  CONCLUSIONS
  This novel mouse animal model of FGR using selective ligation recapitulates multiple characteristics of placental vascular insufficiency (PI) in humans. This is the first non-genetic mouse model of PI which offers its application in transgenic mice to better study the underlying mechanisms in PI.
  
  
  CONCLUSIONS
  A new mouse model of placental vascular insufficiency by selective ligation of mesenteric uterine artery branch recapitulates multiple findings observed in human placental vascular insufficiency.
authors.affiliation: The Fetal Care Center of Cincinnati, Division of Pediatric General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Division of Maternal-Fetal Medicine, Cincinnati, OH, USA; University of Cincinnati College of Medicine, Cincinnati, OH, USA; Good Samaritan Hospital, Cincinnati, OH, USA. Electronic address: drmhabli@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Habli
authors.forename: H
authors.initials: H
authors.lastname: Jones
authors.forename: B
authors.initials: B
authors.lastname: Aronow
authors.forename: K
authors.initials: K
authors.lastname: Omar
authors.forename: T M
authors.initials: TM
authors.lastname: Crombleholme
mesh_terms: D000818:Animals; D001724:Birth Weight; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology*; D018507:Gene Expression Regulation, Developmental; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D021041:Placental Circulation; D010927:Placental Insufficiency / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010929:Placentation; D011247:Pregnancy; D012727:Sex Characteristics; D013002:Somatomedins / Q000235:genetics / Q000378:metabolism; D055988:Uterine Artery / Q000601:surgery; D015430:Weight Gain
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins
keywords: Fetal growth restriction; IGF; Mice animal model; Placental insufficiency