Proliferation of bovine endometrial epithelial cells is promoted by prostaglandin E2-PTGER2 signaling through cell cycle regulation

It is known that prostaglandin E-2 (PGE(2)) induces proliferation of epithelia in bovine endometrial explants, however, the detailed mechanism of regulation of PGE(2) in inducing bovine endometrial epithelial cell (bEEC) proliferation is unclear. In this study, we determined whether proliferation of bEECs is promoted by PGE(2)-prostaglandin E receptor 2 (PTGER2) signaling activation through cell cycle regulation. The results demonstrated that bEECs proliferation was induced by treatment of PGE(2) and PTGER2 agonist butaprost. These processes were down-regulated by PTGER2 antagonist AH6809 and CDK inhibitors (LEE011, CDK2 Inhibitor II and Ro 3306). PGE(2) and butaprost induced cyclins (A, B1, D1, D3 and E2), cyclin-dependent kinases (CDKs, 1, 2, 4 and 6), and epidermal growth factor (EGF) expression were inhibited by AH6809 treatment in bEECs. Moreover, proliferating cell nuclear antigen (PCNA), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and PTGER2 expression in bEECs were up-regulated by PGE(2) and butaprost treatment. Our data demonstrate that PGE(2)-PTGER2 signaling activation has a direct molecular association with cell cycle regulation and cell proliferation in bEECs. Collectively, these findings will improve our understanding of the roles for PGE(2)-PTGER2 signaling activation in the physiological and pharmacological processes of bovine endometrium.