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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Yang
Peixin
P
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
Li
Hua
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005333:Fetus; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy* / Q000201:enzymology; D066298:In Vitro Techniques; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D015017:Yolk Sac / Q000033:anatomy & histology / Q000098:blood supply
D000975:Antioxidants; C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D002392:Catechin; C045651:epigallocatechin gallate; D051057:Proto-Oncogene Proteins c-akt