EFFECTS OF METABOLIC-INHIBITORS ON MOUSE PREIMPLANTATION EMBRYO DEVELOPMENT AND THE ENERGY-METABOLISM OF ISOLATED INNER CELL MASSES

The effects of two metabolic inhibitors, methyl palmoxirate (MP) and a mino-oxyacetate (AOA), on mouse preimplantation embryo development and cell number, and inner cell mass (ICM) cell metabolism have been exam ined. Two-cell embryos were cultured in media supplemented with either MP, which inhibits fatty acid oxidation, or AOA, which inhibits the t ransamination of glutamate into alpha-ketoglutarate. Embryos were scor ed for development daily. On day 5, expanded blastocysts were differen tially labeled with fluorochromes to visualize TE and ICM cell nuclei, or the ICMs isolated by immunosurgery and their energy metabolism det ermined using microfluorometric methods. Embryos exposed to the two in hibitors developed into fully expanded blastocysts, although cell numb ers of both the TE and ICM cells were significantly reduced compared t o controls. The uptake of glucose in the presence of 1 mM MP or AOA di d not differ from the controls, but less glucose was accountable for b y lactate production. MP significantly reduced lactate production. In the presence of 4 mM AOA, the amount of glucose oxidized and the amoun t of lactate formed by ICMs were significantly reduced. The results in dicate that the fuels used by isolated mouse ICMs vary in response to substrate availability and that fatty acids may be a potential energy source. (C) 1996 Wiley-Liss, Inc.