This paper is only available as a PDF. To read, Please Download here.
Abstract
OBJECTIVES: It has recently been suggested that oxygen free radicals are involved in the high
incidence of fetal dysmorphogenesis that is associated with diabetic pregnancies.
The purpose of the current investigation was to study the effect of copper zinc superoxide
dismutase, a free radical scavenging enzyme, on the prevention of diabetes-associated
embryopathy in mice.
STUDY DESIGN: Mice used in this study were either transgenic, bearing the human copper zinc superoxide
dismutase gene, or nontransgenic controls. Diabetes was generated by streptozotocin
administration on days 6 and 7 of gestation. Hyperglycemia developed on day 8 and
was maintained through day 10 (critical period of organogenesis). On day 10 fetuses
were examined for external anomalies, and their crown-rump lengths and deoxyribonucleic
acid content were determined. RESULTS: Induction of maternal diabetes produced a significant reduction in mean crown-rump
length of control embryos (4.48 ± 0.7 mm vs 3.65 ± 0.6 mm, p = 0.0001), whereas trangenic embryos were not affected (4.72 ± 0.6 mm vs 4.45 ± 0.8
mm, p > 0.05). After induction of diabetes fetal loss and malformation rates were significantly
higher in control embryos (6.0% vs 23.8% and 8.4% vs 16.5%, respectively). Transgenic
embryos were practically unaffected by diabetes and showed fetal loss and malformation
rates of 5.9% and 4.4%, respectively, after induction of diabetes.
CONCLUSIONS: Elevated levels of copper zinc superoxide dismutase, a key enzyme in the metabolism
of free oxygen radicals, elicit a protective effect against diabetes-associated embryopathy.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to American Journal of Obstetrics & GynecologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- The prevention of diabetes associated birth defects.Semin Perinatol. 1987; 12: 292-296
- Gestational diabetes mellitus.N Engl J Med. 1986; 315: 1025-1026
- Increased incidence of congenital malformations in the offspring of diabetic rats and their prevention by maternal insulin therapy.Diabetes. 1982; 31: 1-6
- Relationship between hemoglobin A1c in early type I (insulin-dependent) diabetic pregnancy and the occurrence of spontaneous abortion and fetal malformations in Sweden.Diabetologia. 1990; 33: 100-104
- Evidence for multifactorial origin of diabetes-induced embryopathies.Diabetes. 1989; 38: 70-74
- Ultrastructural analysis of malformations of the embryonic neural axis induced by hyperglycemia conceptus culture.Teratology. 1985; 32: 363-373
- Maternal diabetes induces increased expression of extracellular matrix components in rat embryos.Diabetes. 1993; 42: 975-980
- Diabetes mellitus and free radicals.Br Med Bull. 1993; 49: 642-652
- Does free oxygen radical increased formation explain long term complications of diabetes mellitus?.Med Hypotheses. 1989; 29: 47-50
- Oxygen radicals, hydrogen peroxide, and oxygen toxicity.in: Pryor WA Free radicals in biology. Academic Press, Orlando1976: 239-277
- Diabetes and embryonic malformations: role of substrate-induced free-oxygen radical production in dysmorphogenesis in cultured rat embryos.Diabetes. 1993; 42: 411-419
- Protection by free oxygen radical scavenging enzymes against glucose induced embryonic malformations in vitro.Diabetologia. 1991; 34: 325-331
- Transgenic mice with increased Cu/Zn-superoxide dismutase activity: animal model of dosage effects in Down syndrome.in: 4th ed. Proc Natl Acad Sci U S A. 84. 1987: 8044-8048
- Gene dosage of CuZnSOD and Down's syndrome: diminished prostaglandin synthesis in human trisomy 21, transfected cells and transgenic mice.EMBO J. 1991; 10: 2119-2124
- Superoxide dismutase: improved assays and an assay applicable to acrylamide gels.Anal Biochem. 1986; 44: 276-287
- Malformations in infants of diabetic mothers.Teratology. 1982; 25: 385-394
- Increased superoxide dismutase (SOD) activity in embryos of transgenic mice protects from the teratogenic effects of a diabetic environment.Diabetes. 1993; 42: 85A
- Hydroxyl radical production and autooxidative glycosylation.Biochem J. 1988; 56: 205-212
- Altered mitochondrial morphology in embryos subjected to a diabetic environment.Anat Rec. 1994; 241: 255-267
- Lipid peroxidation in relation to prostacyclin and thromboxane physiology and pathophysiology.Br Med Bull. 1983; 39: 277-280
- Hyperglycemia induced teratogenesis is mediated by a functional deficiency of arachidonic acid.in: 4th ed. Proc Natl Acad Sci U S A. 82. 1985: 31
- Effect of hyperglycemia on sorbitol and myo-inositol content of cultured rat conceptus: failure of aldose reductase inhibitors to modify myo-inositol depletion and dysmorphogenesis.Biochem Biophys Acta Res Commun. 1986; 140: 974-980
- Arachidonic acid prevents hyperglycemia-associated yolk sac damage and embryopathy.Am J Obstet Gynecol. 1986; 155: 691-702
- Phase II trial of copper zinc superoxide dismutase (CuZn-SOD) in the treatment of Crohn's disease.Free Radic Res Commun. 1991; 12–13: 563-569
- Superoxide dismutase prevents lipid peroxidation in burned patients.Burns. 1990; 16: 406-408
Article Info
Footnotes
☆Presented at the Fifteenth Annual Meeting of the Society of Perinatal Obstetricians, Atlanta, Georgia, January 23–28, 1995.
Identification
Copyright
© 1995 Published by Elsevier Inc.
