title: Maternal citrulline supplementation enhances placental function and fetal growth in a rat model of IUGR: involvement of insulin-like growth factor 2 and angiogenic factors.
abstract: OBJECTIVE
  To determine the effects of maternal citrulline supplementation on fetal growth and placental efficiency in a rat model of intrauterine growth restriction (IUGR) induced by maternal protein restriction.
  
  
  METHODS
  Pregnant Sprague-Dawley rats were randomly assigned to three groups: NP (receiving a control 20% protein diet), LP (a 4% protein diet), or LP-CIT (an LP diet along with L-citrulline, 2 g/kg/d in drinking water). On the 15th and 21st day of gestation (GD15 and GD21, respectively), dams underwent a C-section, by which fetuses and placentas were extracted. The expression of genes involved in placental growth and angiogenesis was studied by quantitative RT-PCR.
  
  
  RESULTS
  Maternal citrulline supplementation increased fetal weight at GD21, and fetal weight/placental weight ratio, an index of placental efficiency, from mid gestation (p < 0.001). The expression of Igf2-P0, a placenta-specific variant of insulin-like growth factor 2 (Igf2) gene, and Vegf and Flt-1, involved in angiogenic pathways, was enhanced in the LP-CIT group (versus NP, p < 0.001, p < 0.01, and p < 0.05 for Igf2-P0, Vegf, and Flt-1, respectively).
  
  
  CONCLUSIONS
  In a model of IUGR induced by protein deprivation, citrulline enhances fetal growth, placental efficiency, and the expression of genes involved in angiogenesis. The relevance of such effect in human pregnancies complicated by IUGR warrants further study.
authors: a UMR PHAN, INRA, & Université de Nantes, IMAD, CRNH-Ouest , Nantes , France.|b Department of Gynecology and Obstetrics , CHU de Nantes , Nantes , France.|c Department of Gynecology and Obstetrics , University of Medicine and Pharmacy , Ho Chi Minh City , Vietnam , and.
authors: Nhat-Thang
authors: NT
authors: Tran
authors: a UMR PHAN, INRA, & Université de Nantes, IMAD, CRNH-Ouest , Nantes , France.
authors: Valerie
authors: V
authors: Amarger
authors: a UMR PHAN, INRA, & Université de Nantes, IMAD, CRNH-Ouest , Nantes , France.
authors: Aurelie
authors: A
authors: Bourdon
authors: b Department of Gynecology and Obstetrics , CHU de Nantes , Nantes , France.
authors: Emilie
authors: E
authors: Misbert
authors: a UMR PHAN, INRA, & Université de Nantes, IMAD, CRNH-Ouest , Nantes , France.
authors: Isabelle
authors: I
authors: Grit
authors: a UMR PHAN, INRA, & Université de Nantes, IMAD, CRNH-Ouest , Nantes , France.|b Department of Gynecology and Obstetrics , CHU de Nantes , Nantes , France.
authors: Norbert
authors: N
authors: Winer
authors: a UMR PHAN, INRA, & Université de Nantes, IMAD, CRNH-Ouest , Nantes , France.|d Nutrition Support Team, IMAD , CHU de Nantes , Nantes , France.
authors: Dominique
authors: D
authors: Darmaun
mesh_terms: D000818:Animals; D002956:Citrulline / Q000494:pharmacology / Q000627:therapeutic use*; D019587:Dietary Supplements; D005260:Female; D005317:Fetal Growth Retardation / Q000517:prevention & control*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010920:Placenta / Q000187:drug effects*; D011247:Pregnancy; D017207:Rats, Sprague-Dawley
chemical_list: D002956:Citrulline
keywords: Amino acids; angiogenesis; growth factor; placenta; transporter