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

• Published in: Molecular and cellular endocrinology 2012-01, Vol.348 (1), p.211-223
• Main Authors: Lee, JeHoon, Banu, Sakhila K., Nithy, Thamizh K., Stanley, Jone A., Arosh, Joe A.
• Format: Article
• Language: English
• Subjects: Animals; Cells, Cultured; Early pregnancy; Endometrium; Endometrium - cytology; Endometrium - metabolism; Epithelial Cells - metabolism; Estrous cycle; Estrous Cycle - genetics; Estrous Cycle - metabolism; Female; Gene Expression; Gene Expression Regulation; Interferon tau; Interferon Type I - pharmacology; Interferon Type I - physiology; Male; PGE2 receptors; Phosphorylation; Pregnancy; Pregnancy Proteins - pharmacology; Pregnancy Proteins - physiology; Protein Kinases - metabolism; Receptors, Prostaglandin E - genetics; Receptors, Prostaglandin E - metabolism; Receptors, Prostaglandin E, EP2 Subtype - genetics; Receptors, Prostaglandin E, EP2 Subtype - metabolism; Receptors, Prostaglandin E, EP4 Subtype - genetics; Receptors, Prostaglandin E, EP4 Subtype - metabolism; Ruminantia; Ruminants; Sheep; Signal Transduction; Stromal Cells - metabolism
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2011.08.020

► 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 PGE 2 signaling in the ovine endometrium. Prostaglandin E2 (PGE 2) 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 PGE 2 signaling in endometrial functions and establishment of pregnancy in ruminants.