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

Abstract

Abstract Recognition and establishment of pregnancy involve several molecular and cellular interactions among the conceptus, uterus, and corpus luteum (CL). In ruminants, interferon-τ (IFNτ) of embryonic origin is recognized as the pregnancy recognition signal. Endometrial prostaglandin F2α (PGF2α) is the luteolysin, whereas PGE2 is considered a luteoprotective or luteotrophic mediator at the time of establishment of pregnancy. The interplay between IFNτ 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 PGF2α, 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 PGF2α receptors. IFNτ 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 PGF2α receptor expression in any of these tissues. In endometrium, IFNτ decreases PGFS in epithelial cells and increases EP2 in stroma. In myometrium, IFNτ decreases PGFS and increases EP2 in smooth muscle cells. In CL, IFNτ increases PGES and decreases EP3. Together, our results show that IFNτ 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 PGF2α, but also on increased PGE2 production in cattle.