Maternal diabetes induces FoxO1 and connexin 43 alterations in the heart of the developing embryo

HUGO SATO, SABRINA ROBERTI, DANIEL MUSIKANT, ALICIA JAWERBAUM, ROMINA HIGA

Buenos Aires

Congreso; International Federation of Placenta Associations; 2019

International Federation of Placenta Associations

Background: Maternal diabetes affects the embryonic, fetal and perinatal development and programs metabolic and cardiovascular alterations in the adult offspring. We recently reported cardiovascular alterations related to the FoxO1 pathway and in connexin43 levels in the adult offspring from diabetic rats.Both FoxO1, a transcription factor essential in nascent vascular development and connexin43, the structural subunit of gap junction and hemichannels, have important roles in cardiovascular development. Matrix metalloproteinase-2 (mmp-2) is a FoxO1 target gene that can reduce connexin43 levels. We hypothesized that there are alterations in connexin43, FoxO1 pathway and its target genes in the developing embryonic hearts of diabetic rats.Methods: The experimental model of diabetes was obtained by streptozotocin administration to adult rats (50mg/kg). Control and diabetic rats were mated with healthy males and at day 12 of pregnancy, embryonic hearts were collected and stored for western blot, qPCR and immunohistochemical studies. Results: Total FoxO1 expression was increased (133%, p