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Effect of Interferon- on Prostaglandin Biosynthesis, Transport, and Signaling at the Time of Maternal Recognition of Pregnancy in Cattle: Evidence of Polycrine Actions of Prostaglandin E₂

Unité d’Ontogénie et Reproduction, Centre Hospitalier Universitaire de Québec, Centre Hospitalier de l’Université de Laval, Centre de Recherche en Biologie de la Reproduction (J.A.A., S.K.B., P.C., M.A.F.), and Département d’Obstétrique et Gynécologie, Université Laval (M.A.F.), Québec, Canada G1K 7P4; and Departments of Plant and Animal Sciences, Nova Scotia Agricultural College (S.K., L.A.M.), Truro, Nova Scotia, Canada B2N 5E3

Address all correspondence and requests for reprints to: Dr. Michel A. Fortier, Unité d’Ontogénie et Reproduction, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Centre Hospitalier de l’Université de Laval, 2705 boulevard Laurier, Ste-Foy, Québec, Canada GIV 4G2. E-mail: mafortier{at}crchul.ulaval.ca.

Recognition and establishment of pregnancy involve several molecular and cellular interactions among the conceptus, uterus, and corpus luteum (CL). In ruminants, interferon- (IFN) of embryonic origin is recognized as the pregnancy recognition signal. Endometrial prostaglandin F₂ (PGF₂) is the luteolysin, whereas PGE₂ is considered a luteoprotective or luteotrophic mediator at the time of establishment of pregnancy. The interplay between IFN and endometrial PGs production, transport, and signaling at the time of maternal recognition of pregnancy (MRP) is not well understood. We have studied the expression of enzymes involved in metabolism of PGE₂ and PGF₂, cyclooxygenase-1 (COX-1) and COX-2, PG synthases (PGES and PGFS), PG 15-dehydrogenase, and PG transporter as well as PGE₂ (EP2 and EP3) and PGF₂ receptors. IFN influences cell-specific expression of COX-2, PGFS, EP2, and EP3 in endometrium, myometrium, and CL in a spatio-temporal and tissue-specific manner, whereas it does not alter COX-1, PGES, PG 15-dehydrogenase, PG transporter, or PGF₂ receptor expression in any of these tissues. In endometrium, IFN decreases PGFS in epithelial cells and increases EP2 in stroma. In myometrium, IFN decreases PGFS and increases EP2 in smooth muscle cells. In CL, IFN increases PGES and decreases EP3. Together, our results show that IFN directly or indirectly increases PGE₂ biosynthesis and EP2-associated signaling in endometrium, myometrium, and CL during MRP. Thus, PGE₂ may play pivotal roles in endometrial receptivity, myometrial quiescence, and luteal maintenance, indicating polycrine (endocrine, exocrine, paracrine, and autocrine) actions of PGE₂ at the time of MRP. Therefore, the establishment of pregnancy may depend not only on inhibition of endometrial PGF₂, but also on increased PGE₂ production in cattle.

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