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BOR - Papers in Press, published online ahead of print November 13, 2002.
Biol Reprod 2002, 10.1095/biolreprod.102.008250
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Submitted July 17, 2002
Returned for revision August 23, 2002
Accepted October 7, 2002

Mechanisms of Hormone Action


Influence of Different Isoforms of Recombinant Trophoblastic Interferons on Prostaglandin Production in Cultured Bovine Endometrial Cells

Julie Parent 1, Christian Villeneuve 1, Andrei P. Alexenko 2, Alan D. Ealy 3, Michel A. Fortier 1*
1 Laval University Hospital Center
2 University of Missouri
3 Pennsylvania State University

* To whom correspondence should be addressed. E-mail: mafortier{at}crchul.ulaval.ca.

Abstract

In ruminants, interferon produced by the trophectoderm (IFN-{tau}) is recognized as the embryonic signal responsible for maternal recognition of pregnancy. IFN-{tau} is believed to act by down-regulating estrogen receptors thus preventing appearance of oxytocin receptors responsible for the release of PGF2{alpha} by the endometrium. The present study was undertaken to determine in vitro the biological activities of different IFN-{tau} isoforms and document putative alternate luteotrophic mechanisms. Endometrial cells in primary cultures were treated with five different rIFN-{tau}: 2 ovine isoforms (ro-4 and ro-11) and 3 bovine isoforms (rb-1a, rb-2b and rb-3b). Their effect was quantified by measurement of PGE2 and PGF2{alpha} production by ELISA and induction of COX-2 by Western and Northern analysis and correlated with antiviral activity previously reported. The overall pattern of response to the IFNs tested suggest that low concentrations (<1µg/ml) reduced the production of both PGs and higher concentrations (>1µg/ml) stimulated preferentially PGE2, however exceptions were noted. Isoform rb-2b with high antiviral activity inhibited PGs production in both cell types at all concentrations tested. IFNs rb-1a and ro-11 had similar antiviral activities, inhibited PG at low concentrations and stimulated them at high concentrations. Isoform rb-3b stands out relative to the other IFNs tested as it induced a variable non dose dependent effect on PG production and low antiviral activity. An increase in COX-2 protein expression and messenger was correlated with increased PG production. The results showing two distinct responses to IFN-{tau} depending on its concentration and/or isoform and the absence of correlation with antiviral activity suggest that complex transduction mechanisms are involved.



Key words: Embryo • Female Reproductive Tract • Mechanisms of Hormone Action • Cytokines • Oxytocin


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