Identification of molecules and mechanisms involved in the 'early pregnancy factor' system

Abstract

For a long time the 'early pregnancy factor' has defied molecular definition. First described in 1976, this phenomenon is revealed in vitro by the rosette inhibition assay, in which a lymphocyte-modifying activity in maternal serum is detected within hours of fertilization; it is present for at least the first two-thirds of pregnancy, with continued detection dependent upon the presence of a viable embryo or fetus. It has potential applications in early pregnancy testing, for monitoring fetal well-being and in the study of fertility control. Although the activity detected is one of a complex biological fluid (pregnancy serum) in a complex biological assay, this ability of pregnancy sera to cause increased rosette inhibition titres (RIT) has generally been ascribed to the presence of an 'early pregnancy factor' (EPF). The common usage of the term EPF has implied the existence in pregnancy sera of a unique factor, which has often been assumed to be a novel, pregnancy-specific protein with the unique capacity to induce increased RITs. Recent results render this concept untenable. These studies have begun to identify the molecules and mechanisms which cause the expression of increased RITs. In particular, thioredoxin or thioredoxin-like molecules have been identified as involved in the mechanisms by which pregnancy sera induced increased RITs. As a result, a new paradigm for the EPF phenomenon is presented which helps to resolve many of the enigmatic properties previously ascribed to the so-called 'early pregnancy factor' and which may assist in the further understanding of the molecular mechanisms of communication between embryo and mother prior to implantation.