Related Experiment Videos
Fuel-mediated teratogenesis: biochemical effects of hypoglycemia during neurulation in mouse embryos in vitro
1Department of Cell Biology and Anatomy, School of Medicine, University of North Carolina, Chapel Hill 27599.
Abstract:
Hypoglycemia has been reported to induce congenital malformations and growth retardation in rodent embryos during the period of neural tube closure in vitro. However, the biochemical alterations responsible for the production of the dysmorphogenic effects have not been evaluated. Therefore, the rates of glucose metabolism by glycolysis, citric acid cycle, oxidative pentose phosphate pathway (PPP), and anabolic utilization were evaluated in mouse embryos and extraembryonic membranes using the whole embryo culture technique. Altered glucose metabolism by glycolysis and oxidative PPP, as well as altered anabolic synthesis, were produced by exposure to hypoglycemia. In embryos exposed to mild hypoglycemia (80 mg/dl) altered metabolism by the PPP and an associated effect on nucleic acid synthesis were in part responsible for the dysmorphogenic effects of this treatment. In contrast, severe hypoglycemia (40 mg/dl) appeared to have an immediate effect on glycolytic metabolism in addition to effects on the PPP and nucleic acid synthesis. Therefore, a multifactorial biochemical mechanism contributes to the induction of malformations by severe hypoglycemia in mouse embryos in vitro. Furthermore, the differential effects of moderate vs. severe hypoglycemia on glycolytic metabolism, and possibly energy production, may account for the differences in the severity of these treatments on embryonic growth and the incidence of malformations.
Insights
Hypoglycemia in early development can cause birth defects by altering glucose metabolism. Mild cases affect the pentose phosphate pathway, while severe cases impact glycolysis, leading to malformations in mouse embryos.
Area of Science:
- Developmental biology
- Biochemistry
- Embryology
Background:
- Hypoglycemia is linked to congenital malformations and growth retardation in rodent embryos.
- The specific biochemical pathways disrupted by hypoglycemia during embryonic development remain unclear.
Purpose of the Study:
- To investigate the biochemical alterations in glucose metabolism pathways (glycolysis, citric acid cycle, pentose phosphate pathway, anabolic utilization) in mouse embryos exposed to hypoglycemia in vitro.
- To elucidate the mechanisms underlying hypoglycemia-induced dysmorphogenic effects during early embryonic development.
Main Methods:
- Whole embryo culture technique was used to expose mouse embryos and extraembryonic membranes to varying glucose concentrations (mild: 80 mg/dl, severe: 40 mg/dl).
- Rates of glucose metabolism via glycolysis, citric acid cycle, oxidative pentose phosphate pathway (PPP), and anabolic utilization were quantified.
Main Results:
- Hypoglycemia significantly altered glucose metabolism through glycolysis, the oxidative pentose phosphate pathway (PPP), and anabolic synthesis in mouse embryos.
- Mild hypoglycemia (80 mg/dl) primarily affected PPP metabolism and nucleic acid synthesis, contributing to dysmorphogenic effects.
- Severe hypoglycemia (40 mg/dl) immediately impacted glycolytic metabolism, alongside effects on PPP and nucleic acid synthesis, indicating a multifactorial mechanism.
Conclusions:
- A multifactorial biochemical mechanism involving altered glucose metabolism contributes to severe hypoglycemia-induced malformations in mouse embryos.
- Differential effects of mild versus severe hypoglycemia on glycolysis and potentially energy production explain variations in embryonic growth retardation and malformation incidence.