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Developmental disturbances of the embryo in diabetic pregnancy
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
1999 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Maternal diabetes during pregnancy constitutes an increased risk for congenital malformation in the offspring. Previous studies have suggested that diabetic embryopathy is associated with an excess of reactive oxygen species (ROS) as well as with a disturbance of prostaglandin (PG) metabolism.

We studied the embryonic environment in vivo, and found that the uterine blood flow to the implantation sites was increased in diabetic compared to control rats on pregnancy days 9-12, suggesting that the embryonic developmental disturbances are associated with an increased supply of nutrients in early diabetic gestation. We cultured rat embryos for 48 hours, either in serum from diabetic rats, or in serum from non-diabetic rats with theglucose concentration adjusted to 10 or 30 mmol/l. Serum from insulin treated diabetic rats was more teratogenic than normal serum at low glucose concentration, whereas high glucose concentration in both normal and diabetic serum caused embryonic dysmorphogenesis. Addition of radical scavengers, such as superoxide dismutase (SOD) and N-acetylcysteine (NAC), to the teratogenic culture medium diminished the rate of embryonic dysmorphogenesis. Inhibitors of the cyclooxygenase (COX) enzyme, indomethacin and acetylsalicylicacid, induced major disturbances in embryos cultured in low glucose concentration. Supplementation of arachidonic acid and PGE2, as well as the ROS scavengers NAC and SOD, prevented the malformations caused by both high glucose levels and COX inhibitors. COX-2 gene expression was decreased on gestational days 9-10 in embryos subjected to high glucose concentration in vitro or diabetes in vivo, which yielded decreased PGE2 levels during neural tube closure.

In conclusion, these studies suggest that increased supply of maternal nutrients and alterations of insulin, glucose, b- hydroxybutyrate, several amino acids in the embryonic environment predispose to embryonic maldevelopment. Furthermore, excess of ROS and inhibition of the PG biosynthesis are likely to be involved in the teratogenic process of diabetic pregnancy.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 1999. , 50 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 858
Keyword [en]
Cell biology, diabetes, pregnancy, embryo, malformation, glucose, ROS, SOD, NAC, prosta- glandin, COX, COX inhibitor, gene expression
Keyword [sv]
National Category
Cell and Molecular Biology
Research subject
Medical Cell Biology
URN: urn:nbn:se:uu:diva-353ISBN: 91-554-4513-6OAI: oai:DiVA.org:uu-353DiVA: diva2:163141
Public defence
1999-09-22, Sal B21, BMC, Uppsala universitet, Uppsala, 09:15
Available from: 1999-09-01 Created: 1999-09-01Bibliographically approved

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