Maternal treatments with a mitochondrial antioxidant prevent the intrauterine programming of alterations in ppargamma and its coactivator pgc-1alpha in the fetal liver of rats that develop gestational diabetes

FORNES D, HIGA R, CAPOBIANCO E, JAWERBAUM, A

Buenos Aires

Congreso; Scientific Meeting of the International Association of the Diabetes and Pregnancy Study Group. Buenos Aires, Marzo 2016; 2016

IADPSG

Maternal diabetes induces a pro-inflammatory environment and impairments in PPARs signaling, evident in both fetuses and placentas. This has been observed in a newly developed experimental model of gestational diabetes (GDM) induced by intrauterine programming. PPARgamma and its coactivator PGC-1alpha regulate developmental, metabolic, anti-oxidant and anti-inflammatory processes. Idebenone is a coenzyme Q analog that works as an electron carrier in the electron transfer chain and as a mitochondrial antioxidant. Improper development of the fetal liver can lead to adult metabolic diseases. Aims: To evaluate whether maternal treatments with idebenone (F0) regulate PPARgamma, PGC-1alpha, peroxynitrite-induced damage and matrix metalloproteinase 2 (MMP-2) levels in the fetal liver of GDM rats (F1). Methods: Mild diabetes was induced in Wistar rats by neonatal streptozotocin administration (90 mg/Kg) (glycemia values 180-230 mg/dl) (F0), an experimental model of diabetes that programs GDM in the F1 generation (glycemia values before pregnancy: 90-100 mg/dl; glycemia values on pregnancy: 130-150 mg/dl). F0 control and diabetic rats were treated with idebenone (100 mg/kg/day) or vehicle during pregnancy. F1 rats were mated with control males and received no treatment. On day 21 of gestation F1 rats were euthanized and the fetal livers isolated for evaluation of PPARgamma, PGC1alpha, nitrotyrosine (indicating protein nitration and peroxynitrite-induced damage) and MMP2 levels by immunohistochemistry. Results: Fetal livers from GDM rats showed a decrease in PPARgamma levels (30%, p