Early Pregnancy Factor (EPF): A Link between Fertilization and Immunomodulation

Abstract

Early pregnancy factor (EPF) is a pregnancy-dependent, suppressor-releasing hormone, which can be differentiated from other known pregnancy-associated substances by its physiological, biochemical and immunological characteristics. To date studies have shown that the presence of EPF in serum at anytime except during pregnancy is pathological and is associated with tumors of germ cell origin.EPF can be detected in serum within hours of fertilization, thus providing for the first time a means of monitoring in vitro the continuing viability of a fertilized egg in vivo. EPF has been shown to be a link between fertilization and immunomodulation. Fertilization of the ovum initiates a chain of events which includes production of EPF. EPF then binds to lymphocytes; releasing soluble suppressor substances, which in turn modulate the mother's immune system. Thus it is proposed that the conceptus ensures its own defence against immunological rejection.

Identification of a putative inhibitor of early pregnancy factor in mice

“…The range ofconcentrations over which EPF is able to affect lymphocytes is thus extended, suggesting a possible biological function for the regulator. That this substance does have a role is reinforced by the observation that production of the inhibitor is under hormonal control, being produced by the oviduct during oestrus and early pregnancy (Morton et ai, 1980; see also Morton (1984) for an illustration of the effect of the oestrous cycle on EPF-A in serum). A larger Mr binding protein (or group of proteins; Mr > 100 000) also associates with EPF in serum during the pre-and periimplantation period.…”

Synthesis of early pregnancy factor using red deer (Cervus elaphus) as a delayed implantation model

“…In this retrospective analysis we have determined that EPF is synthesized in the red deer (Cervus elaphus) and is consistent with reports from other species (1-5). However, during our investigations, it became apparent that the biphasic response of increased EPF previously associated with the periimplantation period in other mammals (8)(9)(10) was associated with blastocyst formation and not implantation. As there is a well-defined period between blasto-cyst formation and implantation in the red deer (11-13), it was possible to determine clearly that the biphasic switch, which increases EPF synthesis, was blastocyst mediated and did not occur during implantation.…”

“…This change in EPF synthesis can be detected by a biphasic response using the rosette inhibition test, which indicates an increase in EPF synthesis (8)(9)(10). However, as blastocyst development in most mammals is closely associated with implantation, it has been difficult to identify whether the proposed switch in EPF synthesis from the ovary is associated with blastocyst development, implantation, or both events.…”

Demonstration of Early Pregnancy Factor in Gilts During the Reproductive Cycle

“…Investigations into the presence of EPF in blood serum of women~ for example~ made it possible to detect the mechanism of action of intrauterine devices during early pregnancy (Smart et al 1982) and to define more clearly the contribution of embryonic death to prenatal losses (Smart et al 1982a;Morton 1984). This factor appears in blood serum shortly after conception (in 4 to 6 hours in mice - Morton et al 1976; in 6 hours in sheep - Morton et al 1979; in about 48 hours in women - Morton et al 1979; after 4 hours in sows - Koch et al 1982).…”