Antagonists of embryo-derived platelet-activating factor act by inhibiting the ability of the mouse embryo to implant

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Abstract
This study utilized the transfer of preimplantation embryos to pseudo-pregnant mice to determine whether PAF-antagonists act primarily on the maternal or embryonic components of implantation. The first experiment used reciprocal embryo transfers, in which blastocysts from mice treated with PAF antagonist (SRI 63-441) or saline (controls), from Days 1 to 4 of pregnancy, were transferred to Day-3 pseudo-pregnant recipients which were also treated with SRI 63-441 or saline on Days 1-4 of pregnancy. The antagonist (40 .mu.g) was administered at 16:00 h on Day 1 and at 09:00 h on Days 2-4 of pregnancy. The percentage of the transferred embryos which implanted was determined on Day 8 of pregnancy. Treatment of the recipient or the donor female with SRI 63-441 resulted in a reduction in implantation rate, from a control level of 45% to 33.8% or 34.7% (P < 0.0002, P < 0.007) respectively. These results suggest that the PAF antagonist affected implantation at the embryonic and maternal levels. However, when the blastocysts were transferred to Day-4 pseudopregnant recipients, treatment of the donor female had a dramatic effect on the implantation rate, resulting in a reduction of 64% (from 40% to 14.3%, P < 0.04), while treatment of the recipient female had no significant effect. In this later experiment the transferred embryos were exposed to the recipient uterine environment for a shorter period before implantation. These results suggest that PAF antagonists affected implantation at the embryonic level and did not adversely affect maternal physiology. Treatment of pseudopregnant females with PAF antagonist failed to inhibit the deciduogenic response to an intrauterine instillation of paraffin oil, while supplementing embryo culture medium with iloprost, SRI 63-441 or WEB 2086 caused a marked and dose-dependent inhibition of trophoblast outgrowth by blastocysts in vitro. These results were consistent with PAF antagonists having actions at the embryonic rather than the maternal level and support previous suggestions that embryo-derived PAF acts as an essential autocrine growth factor for the early embryo.
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