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Prevention of diabetes-associated embryopathy by overexpression of the free radical scavenger copper zinc superoxide dismutase in transgenic mouse embryos
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 transgenic 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.
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“Burton (2009) reported that in animals with genetically impaired antioxidant enzyme activity and in diabetic rats in whom ROS levels were increased, the offspring had congenital abnormalities (Hagay et al. 1995;Eriksson, 1999;Nicol et al. 2000).”
From Iron, Oxidative Stress and Health (2012) · cites this paper as Hagay et al. 1995
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Metadata
- Authors
- Hagay, Z. J., Weiss, Y., Zusman, I., Peled-Kamar, M., Reece, E. A., Eriksson, U. J., & Groner, Y.
- Affiliations
- Kaplan Medical Center (IL)
- Weizmann Institute of Science (IL)
- Hebrew University of Jerusalem (IL)
- Temple University (US)
- Uppsala University (SE)
- Corresponding author
- Hagay, Zion J.
- ORCID
- Groner, Yoram
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 1995-10
- Volume
- 173
- Issue
- 4
- Pages
- 1036-1041
- ISSN
- 0002-9378 (ISSN-L)
- OpenAlex
- W2050726467
- Cited by
- 149
- References
- 25
- Citations by year
- 2024: 2 · 2023: 1 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 7 · 2015: 9 · 2014: 9 · 2013: 5 · 2012: 10
- FWCI
- 10.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- copper-zinc superoxide dismutase, oxygen free radicals, transgenic embryos, maternal diabetes, streptozotocin-induced diabetes, fetal death, crown-rump length, organogenesis, antioxidant defense
- MeSH terms
- Congenital Abnormalities, Analysis of Variance, Animals, Diabetes Mellitus, Experimental, Embryo, Mammalian, Female, Humans, Mice, Transgenic, Pregnancy, Pregnancy in Diabetics, Superoxide Dismutase, Gene Expression, Chi-Square Distribution, Odds Ratio, Free Radical Scavengers, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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