Epigallocatechin-3-gallate ameliorates hyperglycemia-induced embryonic vasculopathy and malformation by inhibition of Foxo3a activation.

Abstract

Maternal hyperglycemia increases the risk of congenital malformations. Epigallocatechin-3-gallate (EGCG), a natural antioxidant purified from green tea, inhibits oxidative stress signaling. We propose that EGCG prevents hyperglycemia-induced malformation via inhibition of oxidative stress signaling. The objective of this study is to examine the effect of EGCG on hyperglycemia-induced adverse effects during embryonic development. Day-9 rat conceptuses were cultured under euglycemic (150 mg/dL glucose) and hyperglycemic (300 mg/dL glucose) conditions in the presence or absence of 1 or 10 micromol/L of EGCG. Both 1 and 10 micromol/L of EGCG significantly ameliorated hyperglycemia-induced embryonic vasculopathy and malformations. Hyperglycemia inactivated protein kinase B (Akt) by reducing phosphorylated Akt levels. EGCG reversed the inhibitory effect of hyperglycemia on Akt activation. EGCG also prevented hyperglycemia-reduced phosphorylated Forkhead transcription factor 3a levels. EGCG prevented hyperglycemia-induced embryopathy through inhibition of Forkhead transcription factor 3a activation. This may have been mediated via the activation of Akt. These findings offer the potential for a possible pharmacological prophylaxis for hyperglycemia-induced embryonic malformations.