A diabetes-like environment increases malformation rate and diminishes prostaglandin E(2) in rat embryos: reversal by administration of vitamin E and folic acid
2005 (English)In: Birth defects research. Clinical and molecular teratology, ISSN 1542-0752, Vol. 73, no 7, 506-511 p.Article in journal (Refereed) Published
BACKGROUND: 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 E(2) (PGE(2)) concentration. Furthermore, we studied whether vitamin E and folic acid treatment rectify such alterations. METHODS: 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. RESULTS: 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 PGE(2) concentration. CONCLUSIONS: Diabetes-induced oxidative stress and disturbance of PGE(2) production may contribute to the embryonic dysmorphogenesis in the offspring of diabetic rodents and, thereby, may also have a role in human diabetic embryopathy.
Place, publisher, year, edition, pages
2005. Vol. 73, no 7, 506-511 p.
Abnormalities/prevention & control, Animals, Diabetes Mellitus, Diabetes Mellitus; Experimental/metabolism, Dinoprostone/*metabolism, Embryo/metabolism/pathology, Embryo Culture Techniques, F2-Isoprostanes/metabolism, Female, Folic Acid/administration & dosage/*pharmacology, Male, Pregnancy, Pregnancy in Diabetics/*metabolism, Pregnancy; Animal, Rats, Rats; Sprague-Dawley, Vitamin E/administration & dosage/*pharmacology
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-22909DOI: 10.1002/bdra.20145PubMedID: 15959876OAI: oai:DiVA.org:uu-22909DiVA: diva2:50682