AJP - Endocrinology and Metabolism, Vol 257, Issue 2 E269-E276, Copyright © 1989 by American Physiological Society
Fuel-mediated teratogenesis: biochemical effects of hypoglycemia during neurulation in mouse embryos in vitro
E. S. Hunter 3rd and T. W. Sadler
Department of Cell Biology and Anatomy, School of Medicine, University of North Carolina, Chapel Hill 27599.
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.
