title: A novel rat model of gestational diabetes induced by intrauterine programming is associated with alterations in placental signaling and fetal overgrowth.
abstract: A family history of diabetes predisposes to gestational diabetes mellitus (GDM). We hypothesized that female offspring of rats with pre-gestational diabetes will develop GDM, a pathology associated with fetal overgrowth and altered placental signaling. We found normal glycemia and insulinemia in the offspring from pre-gestational diabetic rats at three months of age. However, consistent with GDM, maternal hyperglycemia and hyperinsulinemia and increased fetal weight were evident when compared to controls. In this intrauterine programmed GDM model, the placentas showed alterations in mTOR pathway: unchanged phosphorylation of 4EBP-1 and PKCα despite reduced total expression of 4EBP-1 and PKCα, and increased phosphorylation of SGK1. GDM placentas also showed reduced expression of PPARα and PPARγ, and increased lipoperoxidation, nitric oxide production and peroxynitrite-induced damage. We conclude that exposure of maternal diabetes in utero programs GDM in the female offspring, leading to a GDM model associated with impaired placental signaling pathways, increased pro-oxidant/pro-inflammatory environment and fetal overgrowth.
authors.affiliation: Laboratory of Reproduction and Metabolism, CEFYBO. CONICET School of Medicine, University of Buenos Aires, Argentina.
authors.forename: Evangelina
authors.initials: E
authors.lastname: Capobianco
authors.affiliation: Laboratory of Reproduction and Metabolism, CEFYBO. CONICET School of Medicine, University of Buenos Aires, Argentina.
authors.forename: Daiana
authors.initials: D
authors.lastname: Fornes
authors.affiliation: Laboratory of Reproduction and Metabolism, CEFYBO. CONICET School of Medicine, University of Buenos Aires, Argentina.
authors.forename: Ivana
authors.initials: I
authors.lastname: Linenberg
authors.affiliation: Section of Neonatology, Department of Pediatrics Department of OB/GYN, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA; Division of Reproductive Sciences, Department of OB/GYN, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Powell
authors.affiliation: Division of Reproductive Sciences, Department of OB/GYN, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jansson
authors.affiliation: Laboratory of Reproduction and Metabolism, CEFYBO. CONICET School of Medicine, University of Buenos Aires, Argentina. Electronic address: a.jawerbaum@gmail.com.
authors.forename: Alicia
authors.initials: A
authors.lastname: Jawerbaum
mesh_terms: D000818:Animals; D016640:Diabetes, Gestational / Q000209:etiology* / Q000378:metabolism*; D005260:Female; D047109:Fetal Development; D018507:Gene Expression Regulation, Developmental; D015227:Lipid Peroxidation; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D011257:Pregnancy Proteins; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases
keywords: Gestational diabetes mellitus; Intrauterine programming; PPAR; Placenta; mTOR