Maternal treatments with a mitochondrial antioxidant prevents alterations in transcriptional regulators of metabolic and antioxidant responses in embryos from diabetic rats

ROMINA HIGA; SABRINA ROBERTI; MARÍA BELEN MAZZUCCO; ALICIA JAWERBAUM

Mar del Plata

Congreso; VI Latin American Symposium on Maternal Fetal Interaction and Placenta (SLIMP); 2015

Maternal diabetes induces an increase in embryo malformations and oxidative stress has been suggested to have a teratogenic role. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor that activates antioxidant cellular response. The transcriptional coactivator PPARg coactivator-1a (PGC-1a) is a master regulator of cellular energy that can regulate mitochondrial function and biogenesis. Idebenone is an antioxidant acting as a transporter in the electron transport chain of mitochondria. Aims: To analyze the effect of idebenone administration to control and diabetic pregnant rats on TNFa, NRF2 and PGC-1a expression and peroxynitrite-induced damage in embryos during early organogenesis. Methods: Diabetes was induced by neonatal streptozotocin administration (90 mg/kg). Adult control and diabetic female rats were mated with healthy males. Pregnant rats were treated with idebenone (100 mg/kg) or vehicle from days 0.5 to 10.5 of pregnancy. Embryonic expression of TNFa, NRF2 and PGC-1a was measured by PCR and nitrotyrosine levels, which indicate peroxynitrite-induced damage, by immunohistochemistry. Results: We found increased expression of TNFa (p