A description of the basic system of components in pregnant mice sera responsible for 'early pregnancy factor' activity

Abstract

The supernatant and pellet retentate fractions obtained from sera from pregnant mice by ammonium sulfate fractionation and extensive dialysis cannot alone induce increased rosette inhibition titres in the rosette inhibition assay. In combination, however, the mixtures can induce increased rosette inhibition titres mimicking the activity of pregnancy sera previously ascribed to the early pregnancy factor. The studies described herein demonstrated that the supernatant retentate fractions derived from sera of pregnant mice were functionally equivalent to a platelet-activating factor (PAF) or a serum stimulus because they stimulated the spleen cells used in the assay to produce active moieties and cooperated with pure thioredoxin in allowing for expression of activity. Conversely, the pellet retentate fractions obtained from sera of pregnant mice were shown to be functionally equivalent to thioredoxin in that they cooperated with a PAF stimulus to allow for the expression of increased rosette inhibition titres. The supernatant retentate fractions obtained from sera from male mice were found to be functionally equivalent to the corresponding supernatant retentate fractions obtained from sera from pregnant mice in stimulating the production of active moieties and in cooperating with thioredoxin or the pellet fractions derived from sera from pregnant mice in allowing for increased rosette inhibition titres. The pellet retentate fractions obtained from male mouse sera, however, were not functionally equivalent to either thioredoxin or the corresponding pellet retentate fractions obtained from pregnancy sera. Consideration of these data led to a basic description of the system of components in pregnancy sera which is responsible for the expression of early pregnancy factor activity.

Expression and localisation of thioredoxin in mouse reproductive tissues during the oestrous cycle

“…The possible involvement of this powerful redox control system in reproductive processes is of particular interest since the discovery of its role in the``early pregnancy factor'' system (Clarke et al, 1991;Tonissen et al, 1993;Orozco et al, 1994). More recently using immunocytochemical techniques to localise thioredoxin in the early human placenta, we (Perkins et al, 1995) and others (Kobayashi et al, 1995) found very high and speci®c expression of thioredoxin by the cytotrophoblast cells.…”

Signal Transduction of hCG Induces Decidualization and Uterine Receptivity

“…Among the number of possible embryo-derived signals known to regulate the endometrial response to the pre-implanting embryo (PIF, EPF, EGF, interleukins, hCG) [11,12], we will recapitulate here some of the recent insights about hCG and signal transduction systems of uterine receptivity. A possible interfering action on this signal transduction is played by gonadotropins used for controlled ovarian hyper-stimulation (COH).…”

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“…This multifactorial model of the capacity of pregnancy serum to express activity in the bioassay,' rather than needing to "be reinterpreted" (10), has now been substantiated by recent studies (6,11) which defined in principle the basic set of components required, and which explained many of the previously enigmatic characteristics of "EPF" as simply properties of the system of components responsible for activity expression.…”

“…No; it has never been suggested so. Rather, thioredoxin has been shown to be a permissive factor in the system of components that ensures activity expression (11). Chaperonin 10 may be another of the required components.…”