Significant changes in platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) concentration have been observed in rabbit endometrium during the preimplantation period, but, under in vitro conditions, constitutive PAF biosynthesis by isolated endometrial tissues was not easily demonstrable. Relative changes in enzymes involved in the synthesis and metabolism of PAF in the tissues may account for this disparity. In addition, during this period of preimplantation, marked changes in PAF receptor concentration have been noted. The present study examines the factors that may modulate the metabolism of exogenous [³H]PAF in the endometrium of rabbits on day 6 of pregnancy. Since preferential [³H]PAF binding in situ by the glandular epithelial, but not by the stromal, cells was demonstrated, their cell-specific metabolism of exogenous [³H]PAF was also examined. After entry into the endometrial cell, [³H]PAF was rapidly metabolized by the sequential action of cytosolic Ca²⁺-independent acetylhydrolase to [³H]lyso-PAF and this was in turn acylated by membrane-associated transacylase to [³H]alkylacylglycerylphosphorylcholine. PAF resynthesis was not observed and, in stromal cells, there was a significant build-up of [³H]lyso-PAF, suggesting that lyso-PAF:acetyl-CoA acetyltransferase may be a limiting factor. In the glandular epithelial cells, however, there was a significant accumulation of a neutral lipid without a significant build-up of [³H]lyso-PAF or [³H]PAF. The neutral lipid co-migrated with the product of phospholipase C-catalysed metabolism of PAF and authentic 1-O-hexadecyl-2-acetyl-glycerol. In addition, the elution times of phospholipase C digestion of C18 PAF and the neutral lipid produced by cellular metabolism of [³H]PAF, determined by gas chromatography/flame ionization detection, were similar. It seems that it is the synthesis of the neutral lipid from reacetylated [³H]lyso-PAF that prevented [³H]PAF accumulation under in vitro conditions. This is the first documentation of the synthesis of this lipid in the mammalian uterus. The lipid may serve as the precursor for de novo PAF synthesis in the glandular epithelial cells during endometrial proliferation.

In an initial experiment, rabbits were injected i.v. with a platelet-activating factor (PAF) antagonist CV-3988 twice a day on days 5 and 6 of pregnancy. Some inhibition of implantation was observed. This effect could not be reproduced in subsequent experiments at the same or at larger or smaller doses. The non-metabolized analogue of PAF, N-carbamyl-PAF (C-PAF) had an inhibitory effect on implantation only when given at toxic concentrations. When CV-3988 and C-PAF were given together on days 5 and 6, there was no effect on implantation. None of the other PAF antagonists tested – BN52021, SRI63,441, WEB2086 or TCV-309 – at various doses could inhibit implantation when given on the same days of pregnancy. TCV-309, at 0.1 mg kg⁻¹ i.v. given on days 2–4 of pregnancy, was also ineffective. These results provide no clear support for a role of PAF in implantation in rabbits.