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Alpha-lipoic acid reduces congenital malformations in the offspring of diabetic mice
Y Sugimura1, T Murase, K Kobayashi
1Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan.
Background:
The mechanism of diabetes-induced congenital malformation remains to be elucidated. It has been reported that alpha-lipoic acid (LA) prevents neural tube defects (NTDs) in offsprings of rats with streptozotocin-induced diabetes. Here, we evaluate the protective effect of LA against diabetic embryopathy, including NTDs, cardiovascular malformations (CVMs), and skeletal malformations, in mice.
Methods:
Female mice were rendered hyperglycemic using streptozotocin and then mated with normal male mouse. Pregnant diabetic or non-diabetic mice were treated daily with either LA (100 mg/kg body weight) or saline between gestational days 0 and 18. On day 18, fetuses were examined for congenital malformations.
Results:
Plasma glucose levels on day 18 were not affected by LA treatment. No congenital malformations were observed either in the saline-treated or LA-treated non-diabetic group. In the saline-treated diabetic group, 39% of fetuses had external malformations and 30% had NTDs. In the LA-treated diabetic group, the corresponding proportions were 11 and 8%, respectively. LA treatment also decreased the incidence of CVMs from 30-3% and of skeletal malformations from 29-6%.
Conclusions:
We conclude that LA can reduce NTDs, CVMs and skeletal malformations in the offspring of diabetic mice at term delivery.
Insights
Alpha-lipoic acid (LA) significantly reduces birth defects in offspring of diabetic mice. This treatment protected against neural tube defects, cardiovascular malformations, and skeletal malformations, offering a potential therapeutic strategy.
Area of Science:
- Reproductive biology and developmental toxicology
- Endocrinology and metabolic disorders
Background:
- The mechanisms underlying diabetes-induced congenital malformations are not fully understood.
- Previous research suggests alpha-lipoic acid (LA) may prevent neural tube defects (NTDs) in diabetic rat models.
Purpose of the Study:
- To investigate the protective effects of alpha-lipoic acid (LA) against diabetic embryopathy in mice.
- To evaluate LA's impact on NTDs, cardiovascular malformations (CVMs), and skeletal malformations.
Main Methods:
- Female mice were induced with hyperglycemia using streptozotocin and mated.
- Pregnant diabetic and non-diabetic mice received daily LA (100 mg/kg) or saline from gestational days 0-18.
- Fetuses were examined for congenital malformations on day 18.
Main Results:
- LA treatment did not affect plasma glucose levels in diabetic mice.
- Diabetic mice treated with saline showed high incidences of external malformations (39%) and NTDs (30%).
- LA treatment significantly reduced NTDs (8%), CVMs (3%), and skeletal malformations (6%) in offspring of diabetic mice.
Conclusions:
- Alpha-lipoic acid (LA) demonstrates a protective effect against diabetic embryopathy in mice.
- LA effectively reduces the incidence of neural tube defects, cardiovascular malformations, and skeletal malformations.
- LA represents a potential therapeutic agent to mitigate congenital malformations associated with maternal diabetes.
