Oxidative metabolism of energy substrates by preimplantation mouse embryos in the presence of platelet-activating factor.
The effects of exogenous platelet-activating factor (PAF, 0.0186-18.6 microM) on the production of CO2 from [U-14C]glucose and [1-14C]lactate by mouse embryos in vitro were investigated. Two-cell embryos displayed significant dose-dependent responses for both energy substrates. The maximal response was observed at 9.3 microM-PAF for glucose metabolism and 1.86 microM-PAF for lactate with increases of 62% and 18%, respectively, over control treatments. After culture from the 2-cell stage for 72 h in the presence of PAF, the resulting blastocysts exhibited a significant dose-dependent increase in metabolism of lactate. It was also apparent that such embryos were not desensitized to PAF as demonstrated by a further enhancement of the metabolic response after re-exposure to PAF. The specificity of action of PAF was confirmed by the absence of any effect on the oxidative metabolism of glucose by lyso-PAF (a catabolite of PAF) over a concentration range of 0.0202-20.2 microM and by the demonstration that SRI 63-441 (a PAF-receptor antagonist) significantly reduced the amount of CO2 produced from glucose in response to 9.3 microM-PAF and abolished the effect on lactate metabolism in response to 1.86 microM-PAF. These results demonstrate a specific, direct influence of exogenous PAF on the oxidative metabolism of glucose and lactate by the preimplantation mouse embryo and suggest an autocrine role for embryo-derived PAF in early pregnancy.
Ryan
J P
JP
Human Reproduction Unit, Royal North Shore Hospital of Sydney, St Leonards, NSW, Australia.
O'Neill
C
C
Wales
R G
RG
D000818:Animals; D001755:Blastocyst / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D051379:Mice; D010084:Oxidation-Reduction; D010972:Platelet Activating Factor / Q000378:metabolism* / Q000494:pharmacology
D003470:Culture Media; D007773:Lactates; D010972:Platelet Activating Factor; D019344:Lactic Acid; D005947:Glucose