Antagonists of embryo-derived platelet-activating factor prevent implantation of mouse embryos.
Inhibitors of platelet activation, alprazolam, iloprost and SRI 63-441, were used to demonstrate the necessity of embryo-derived platelet-activating factor (PAF) activity for the establishment of pregnancy in mice. In a splenectomized mouse bioassay 6 micrograms alprazolam inhibited, for 3 h, the thrombocytopenia induced by 0.1 micrograms PAF; 4 micrograms iloprost and 0.5 microgram SRI 63-441 were effective for 6 and 12h respectively. The administration of 2 micrograms iloprost/30 g body weight on Days 1 and 4 of pregnancy and twice daily on Days 2 and 3 caused a 50% reduction (P less than 0.0005) in the number of implantation sites in the uterus at Day 8 of pregnancy, without affecting (P greater than 0.05) the number of corpora lutea. A similar reduction in the number of implantation sites was achieved with 20 micrograms SRI 63-441/30 g body weight/day. The reduction in implantation rate was evident on Day 5 of pregnancy by visualizing the implantation sites with pontamine sky blue. SRI 63-441 had no effect on peripheral blood progesterone concentrations from Day 1 to Day 9 of pregnancy, and did not appear to inhibit implantation by blocking the preimplantation surge of oestradiol. The number and morphology of blastocysts flushed from the uterus of Day 4 inhibitor-treated mice was not different (P greater than 0.05) from the controls. The cleavage rate and morphology of embryos cultured from the 2-cell to blastocyst stage in media containing SRI 63-441 or iloprost (10 micrograms/ml) were normal, precluding a gross toxic effect. Simultaneous administration of 1 microgram PAF-acether to treated animals re-established pregnancy rates to levels not significantly different (P greater than 0.05) from the controls.
Spinks
N R
NR
Human Reproduction Unit, Royal North Shore Hospital of Sydney, St Leonards, New South Wales, Australia.
O'Neill
C
C
D000525:Alprazolam / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D010064:Embryo Implantation / Q000187:drug effects*; D011464:Epoprostenol / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood; D005260:Female; D016285:Iloprost; D051379:Mice; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011374:Progesterone / Q000097:blood; D011806:Quinolinium Compounds / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects
D010972:Platelet Activating Factor; D011806:Quinolinium Compounds; C050531:SRI 63-441; D011374:Progesterone; D004958:Estradiol; D011464:Epoprostenol; D016285:Iloprost; D000525:Alprazolam