Early pregnancy induced expression of prostaglandin E2 receptors EP2 and EP4 in the ovine endometrium and regulated by interferon tau through multiple cell signaling pathways

Prostaglandin E2 (PGE2) plays pleiotropic roles at fetal–maternal interface during establishment of pregnancy. The objectives of the study were to: (i) determine regulation of PGE2 receptors EP1, EP2, EP3, and EP4 in the endometrium during the estrous cycle and early pregnancy; and (ii) understand endometrial epithelial and stromal cell-specific hormonal regulation of EP2 and EP4 in sheep. Results indicate that: (i) early pregnancy induces expression of EP2 and EP4 but not EP1 and EP3 proteins in the endometrium on days 12–16 compared to that of estrous cycle; (ii) intrauterine infusion of interferon tau (IFNT) increases expression of EP2 and EP4 proteins in endometrium; and (iii) IFNT activates distinct epithelial and stromal cell-specific JAK, EGFR, ERK1/2, AKT, or JNK signaling module to regulate expression of EP2 and EP4 proteins in the ovine endometrium. Our results indicate a role for EP2 and EP4-mediated PGE2 signaling in endometrial functions and establishment of pregnancy in ruminants.

► Early pregnancy increases expression of EP2 and EP4 proteins in the ovine endometrium.
► Expression of EP2 and EP4 is decreased in the ovine endometrium at luteolysis.
► IFNT induces expression of EP2 and EP4 proteins through multiple pathways in the ovine endometrium.
► EP2 and EP4 additively mediate PGE2 signaling in the ovine endometrium.