Antagonists of embryo-derived platelet-activating factor act by inhibiting the ability of the mouse embryo to implant.
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 micrograms) 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 less than 0.0002, P less than 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Spinks
N R
NR
Human Reproduction Unit, Royal North Shore Hospital of Sydney, St. Leonards, NSW, Australia.
Ryan
J P
JP
O'Neill
C
C
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001755:Blastocyst / Q000187:drug effects*; D003656:Decidua / Q000187:drug effects; D010064:Embryo Implantation / Q000187:drug effects*; D004624:Embryo Transfer; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D016285:Iloprost; D051379:Mice; D008815:Mice, Inbred Strains; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011247:Pregnancy; D011806:Quinolinium Compounds / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles; D014327:Trophoblasts / Q000187:drug effects
D001381:Azepines; D010972:Platelet Activating Factor; D011806:Quinolinium Compounds; D014227:Triazines; D014230:Triazoles; C050531:SRI 63-441; C052518:WEB 2086; D011464:Epoprostenol; D016285:Iloprost