Mitochondrial alterations in embryos exposed to B‐hydroxybutyrate in whole embryo culture

摘要

AbstractThe ketone body B‐hydroxybutyrate (B‐OHB) produces malformations and ultrastructural alterations in mitochondria of mouse embryos exposed for 24 hours to the compound in whole embryo culture. The present study was conducted to establish the time‐course of the mitochondrial changes to determine whether the changes are reversible, and to relate these changes to the malformations produced by the compound. Since mitochondria also play a key role in the metabolism of ketone bodies, the capacity of the early somite embryo to metabolize B‐OHB was investigated in an effort to link the morphological alterations in the mitochondria to a biochemical process. Early somite embryos were cultured 4, 8, or 24 hours in the presence of 32 mM DL‐B‐OHB and then cultured for an additional 24 hours in control serum. Finally, embryonic tissue during the teratogenic period was assessed for its capability to oxidize B‐OHB using D‐(3‐14C)‐B‐OHB. The treated embryos showed progressive alterations in the mitochondria, beginning at 4 hours with a loss of matrix density and culminating at 24 hours with high‐amplitude swelling, complete loss of matrix density, and disappearance of cristae. These alterations were reversible following removal of the embryos after 24 hours of exposure to B‐OHB and culturing for an additional 24 hours in control serum. Metabolism studies demonstrated that the early somite embryo possesses a limited capacity to oxidatively metabolize B‐OHB. The biochemical implications of these findings are discussed with respect to the possible role of ketone bodies in the mechanism of diabetes‐ind