D-(-)-beta-hydroxybutyrate-induced effects on mouse embryos in vitro.

Area of Science:

• Developmental biology
• Metabolic disorders
• Teratology

Background:

• Beta-hydroxybutyrate (BOHB) is a ketone body present during metabolic states like uncontrolled diabetes.
• Maternal ketosis can expose developing embryos to elevated ketone levels.
• The teratogenic effects of the racemic mixture (DL-BOHB) are known, but the specific role of the D-isomer is less understood.

Purpose of the Study:

• To investigate the teratogenic effects of the D-isomer of beta-hydroxybutyrate (D-BOHB) on neurulating mouse embryos.
• To explore the impact of D-BOHB on embryonic metabolism, specifically glucose metabolism via the pentose phosphate pathway (PPP) and Krebs cycle.
• To compare the teratogenicity of D-BOHB with the DL-racemic mixture.

Main Methods:

• Whole embryo culture technique was employed to culture mouse embryos.
• Embryos were exposed to varying concentrations of D-BOHB.
• Embryonic malformations, growth retardation, and glucose metabolism (PPP and Krebs cycle) were assessed.

Main Results:

• D-BOHB induced malformations and growth retardation in a concentration-dependent manner.
• High concentrations of D-BOHB led to neural tube defects and decreased glucose metabolism through the PPP and Krebs cycle.
• D-BOHB showed less teratogenicity than the DL-racemic mixture, suggesting the L-isomer is also teratogenic.

Conclusions:

• D-BOHB can induce developmental abnormalities in embryos, potentially through mechanisms similar to DL-BOHB.
• Embryos may be exposed to teratogenic concentrations of D-BOHB in uncontrolled diabetic pregnancies.
• The teratogenic contribution of the L-isomer of BOHB remains to be elucidated, making a complete assessment of maternal ketosis impact incomplete.