title: The effect of prenatal pravastatin treatment on altered fetal programming of postnatal growth and metabolic function in a preeclampsia-like murine model.
abstract: OBJECTIVE
  Preeclampsia alters fetal programming and results in long-term metabolic consequences in the offspring. Pravastatin has been shown to prevent preeclampsia in animal models. Our aim was to characterize the effects of preeclampsia on fetal programming of adult growth and metabolic function, and evaluate the role of preventive pravastatin therapy, using a well characterized murine model.
  
  
  METHODS
  CD-1 mice were injected through the tail vein with adenovirus carrying soluble fms-like tyrosine kinase 1 (sFlt-1) and randomly allocated to pravastatin (5 mg/kg/day; sFlt-1/prav, n = 7) or water (sFlt-1, n = 6) until weaning. A control group was injected with adenovirus carrying the murine immunoglobulin G2α Fc fragment (mFc, n = 8). Male and female offspring (6-8/group) were weighed every month until 6 months of age. Intraperitoneal glucose tolerance testing was performed after 16 hours of fasting at 3 and 6 months of age; glucose and insulin responses were measured.
  
  
  RESULTS
  sFlt-1 offspring weight was lower than mFc control (P < .001) until 2 months of age for females and 5 months of age for males (P < .001). There were no differences in postnatal growth between mFc and sFlt-1/prav offspring. At 3 and 6 months, female sFlt-1 offspring had higher glucose response compared with mFc and sFlt-1/prav. Three-month-old male sFlt-1 had lower insulin response compared with mFc offspring.
  
  
  CONCLUSIONS
  Preeclampsia alters postnatal growth and metabolic function in the adult offspring in this animal model. Maternal therapy with prav prevents some of these alterations in the offspring.
authors.affiliation: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX.
authors.forename: Mollie
authors.initials: M
authors.lastname: McDonnold
authors.affiliation: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX.
authors.forename: Esther
authors.initials: E
authors.lastname: Tamayo
authors.affiliation: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX.
authors.forename: Talar
authors.initials: T
authors.lastname: Kechichian
authors.affiliation: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX.
authors.forename: Phyllis
authors.initials: P
authors.lastname: Gamble
authors.affiliation: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX.
authors.forename: Monica
authors.initials: M
authors.lastname: Longo
authors.affiliation: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX.
authors.forename: Gary D V
authors.initials: GD
authors.lastname: Hankins
authors.affiliation: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX.
authors.forename: George R
authors.initials: GR
authors.lastname: Saade
authors.affiliation: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX.
authors.forename: Maged M
authors.initials: MM
authors.lastname: Costantine
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D018797:Cell Cycle Proteins; D004195:Disease Models, Animal; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D007328:Insulin / Q000097:blood*; D008297:Male; D051379:Mice / Q000254:growth & development* / Q000378:metabolism; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use*; D011225:Pre-Eclampsia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D011247:Pregnancy; D043562:Receptors, G-Protein-Coupled; D040281:Vascular Endothelial Growth Factor Receptor-1
chemical_list: D001786:Blood Glucose; D018797:Cell Cycle Proteins; C115270:G2A receptor; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D017035:Pravastatin
keywords: fetal programming; metabolic; pravastatin; preeclampsia; weight