PARENT SESSION
Preimplantation Embryo/Fetal Development
181
INFLUENCE OF DIFFERENT ISOFORMS OF RECOMBINANT TROPHOBLASTIC INTERFERONS (rIFN-t) ON PROSTAGLANDIN PRODUCTION IN CULTURED ENDOMETRIAL CELLS.
Villeneuve, Christian1, Parent, Julie1, Alexenko, Andrei2, Ealy, Alan3, Fortier, Michel1, 1 2 3
ABSTRACT- At the time of recognition of pregnancy, interferon produced by the trophectoderm (IFN-t) is recognized as the antiluteolytic signal produced by the embryo. One mechanism of IFN-t action is to down regulate estrogen receptors thus preventing appearance of oxytocin receptors responsible for the release of PGF2a by the endometrium. Because this mechanism requires at least 3 to 4 days of exposure to IFN-t, other mechanisms must be involved because bovine embryos can be transferred as late as day 16 and induce recognition of pregnancy within less than 24 h. The present study was undertaken to quantitate in vitro the biological activities of different IFN-t isoforms and document putative alternate luteotrophic mechanisms. Endometrial cells in primary cultures were treated with 5 different rIFN-t: 2 ovine isoforms (11 and 4) and 3 bovine isoforms (1a, 2b and 3b). Their effect was quantitated by measurement of PGE2 and PGF2a production by ELISA and induction of COX proteins by Western analysis. Globally, low concentrations (<1ug/ml) of IFN-t reduced the production of both PGs and higher concentrations (>1ug/ml) stimulated preferentially PGE2. However, each isoform exhibited distinct dose and cell type dependent responses. The antiviral activities of the IFN tested were reported previously and ranked as follows 4> 2b> 1a> 11 >> 3b. Interestingly, 2b an isoform with high antiviral activity inhibited PG production in both cell types at all concentrations tested. IFNs 1a and 11 had similar antiviral activities, inhibited PG at low concentrations and stimulated them at high concentrations. Isoform 3b stands out by an absence of effect on PG production and low antiviral activity. An increase in COX-2 protein expression was correlated with increased PG production. The results obtained suggest existence of two distinct response to IFN-t depending on its concentration and/or isoform and support the presence of multiple states of the receptor. This may explain the divergence in the results obtained by different laboratories. Supported by NSERC of Canada.
KEY WORDS: Prostaglandins, interferon tau, antiviral activities