Proinflammation in maternal and fetal livers and circulating miR-122 dysregulation in a GDM rat model induced by intrauterine programming

Mol Cell Endocrinol. 2020 Jun 15:510:110824. doi: 10.1016/j.mce.2020.110824. Epub 2020 Apr 18.

Abstract

In gestational diabetes mellitus (GDM) pregnancies, a compromised fetal liver may impact offspring's metabolic health. Here, we aimed to address prooxidant, proinflammatory and profibrotic markers in the livers from GDM rats and their fetuses, and to analyze the expression of miR-122 (a relevant microRNA in liver pathophysiology) in fetal and maternal plasma of GDM rats, as well as in the fetal livers of neonatal streptozotocin-induced (nSTZ) diabetic rats, the rats that generate GDM through intrauterine programming. GDM and nSTZ rats were evaluated on day 21 of pregnancy. We found increased nitric oxide production and lipoperoxidation in the livers from GDM rats and their fetuses compared to controls. Livers from GDM fetuses also showed increased levels of connective tissue growth factor and matrix metalloproteinase-2. The expression of miRNA-122 was downregulated in the plasma from GDM rats and their male fetuses, as well as in the livers from male fetuses of nSTZ diabetic rats. miR-122 levels were regulated both in vitro through PPARγ activation and in vivo through a maternal diet enriched in PPAR ligands. Our findings revealed a prooxidant/proinflammatory environment in the livers from GDM rats and their fetuses and a dysregulation of miR-122, likely relevant in the programming of offspring's diseases.

Keywords: Fetus; Intrauterine programming; Liver; Maternal diabetes; miR-122.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Circulating MicroRNA / blood
  • Circulating MicroRNA / genetics
  • Connective Tissue Growth Factor / metabolism
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / genetics*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes, Gestational / blood
  • Diabetes, Gestational / genetics*
  • Diabetes, Gestational / metabolism
  • Disease Models, Animal
  • Female
  • Fetus / embryology*
  • Gene Expression Regulation*
  • Inflammation / blood
  • Inflammation / genetics*
  • Lipid Peroxidation
  • Liver / embryology*
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Nitric Oxide / biosynthesis
  • Olive Oil
  • Oxidants / metabolism
  • Pregnancy
  • Rats, Wistar
  • Streptozocin
  • Uterus / pathology*

Substances

  • Biomarkers
  • Circulating MicroRNA
  • MIRN122 microRNA, rat
  • MicroRNAs
  • Olive Oil
  • Oxidants
  • Connective Tissue Growth Factor
  • Nitric Oxide
  • Streptozocin
  • Matrix Metalloproteinase 2