Presented in part at the 35th Annual Meeting of the Diabetic Pregnancy Study Group (DPSG), August 29–September 2, 2003, Sant Salvador, Tarragona, Spain.
A diabetes-like environment increases malformation rate and diminishes prostaglandin E2 in rat embryos: Reversal by administration of vitamin E and folic acid†
Article first published online: 15 JUN 2005
Copyright © 2005 Wiley-Liss, Inc.
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume 73, Issue 7, pages 506–511, July 2005
How to Cite
Wentzel, P. and Eriksson, U. J. (2005), A diabetes-like environment increases malformation rate and diminishes prostaglandin E2 in rat embryos: Reversal by administration of vitamin E and folic acid. Birth Defects Research Part A: Clinical and Molecular Teratology, 73: 506–511. doi: 10.1002/bdra.20145
- Issue published online: 6 JUL 2005
- Article first published online: 15 JUN 2005
- Manuscript Accepted: 18 FEB 2005
- Manuscript Received: 17 DEC 2004
- Ernfors Family Fund
- Swedish Diabetes Association
- Juvenile Diabetes Foundation International
- Novo Nordisk Foundation
- Swedish Medical Research Council. Grant Numbers: 12X-7475, 12X-109
- prostaglandin E2;
- oxygen radical(s);
- vitamin E (tocopherol);
- folic acid
Offspring of women with diabetes are at increased risk for congenital malformations and disturbed growth compared with infants from nondiabetic pregnancies. The precise biological process behind these effects is not yet completely clarified. Previous studies have suggested that diabetic embryopathy is associated with increased level of oxidative stress and disturbed arachidonic acid metabolism. The aim of the present study was to investigate whether a diabetes-like environment both in vivo and in vitro increases embryonic levels of isoprostanes and alters embryonic prostaglandin E2 (PGE2) concentration. Furthermore, we studied whether vitamin E and folic acid treatment rectify such alterations.
Embryos from diabetic and nondiabetic rats at gestational days (GDs) 10 and 11 were used. In the in vitro experiments, we used whole embryo culture, which mimics pregnancy. GD 9 embryos from nondiabetic rats were cultured for either 24 hr (corresponding to GD 10) or 48 hr (corresponding to GD 11) and exposed to 10 or 30 mM glucose concentration with or without folic acid.
Embryos from diabetic rats and embryos cultured in a high glucose concentration showed increased malformation rates. Dietary treatment with vitamin E in vivo and supplementation of folic acid in the culture medium with 30 mM glucose in vitro decreased the malformation rate, decreased embryonic isoprostane levels, and increased PGE2 concentration.
Diabetes-induced oxidative stress and disturbance of PGE2 production may contribute to the embryonic dysmorphogenesis in the offspring of diabetic rodents and, thereby, may also have a role in human diabetic embryopathy. Birth Defects Research (Part A), 2005. © 2005 Wiley-Liss, Inc.