Embryo-derived platelet activating factor: interactions with the arachidonic acid cascade and the establishment and maintenance of pregnancy

Two classes of potent lipid mediators are produced by the mouse and human pre-embryo: platelet activating factor (PAF) and prostaglandins (PGs). This paper reviews the evidence for their production by the pre-embryo and for their role in embryo development and the successful establishment of pregnancy. The biosynthesis of PAF and arachidonic acid may be linked, the synthesis of PAF resulting in the generation of arachidonic acid with its subsequent conversion to prostaglandins. Pharmacological inhibitor studies show that a major site of action of PAF is the embryo itself, acting as an embryonic autocrine growth factor, whereas PGs appear to act primarily on maternal tissues although they do modulate some aspects of early embryo metabolism. It is the maternal tissues that are the primary source of PG production in early pregnancy. Maternal PGs have a variety of functions including involvement in the proinflammatory response of early pregnancy and the control of corpus luteum function. In the ewe, pregnancy is associated with an attenuation of oxytocin-induced production of the luteolysin, prostaglandin F2 alpha (PGF2 alpha). PAF can mimic the effect of pregnancy, preventing the release of PGF2 alpha in response to exogenous oxytocin and, when administered into the uterine lumen, extending the life span of the corpus luteum. Thus, embryo-derived PAF appears to have an essential role in the establishment of pregnancy by acting as an autocrine growth factor for the embryo and by exerting a variety of effects on maternal physiology, including modulating maternal prostaglandin secretion and action.