Molecular cloning and characterization of bovine prostaglandin E₂ receptors EP2 and EP4: Expression and regulation in endometrium and myometrium during the estrous cycle and early pregnancy

Prostaglandins (PGs) play important functions in the reproductive system, and PGE₂ appears necessary for recognition of pregnancy. We have found that PGE₂ is able to increase cAMP generation in the bovine endometrium. There are two PGE₂ receptors (EP), EP2 and EP4, that are coupled to adenylate cyclase to generate cAMP, but these receptors have not been studied in the bovine. We have cloned and characterized bovine EP2 and EP4 receptors and studied their expression in the uterus. The amino acid sequences of bovine EP2 and EP4 possess a high degree (>80%) of identity with the other mammalian homologs. EP2 is expressed in most tissues, and EP4 is expressed only in intestine and testis. EP2 mRNA and protein are expressed in endometrium and myometrium during the estrous cycle, whereas EP4 is undetectable. The Western analysis indicates that EP2 is maximally expressed in both endometrium and myometrium between d 10 and 18 of the estrous cycle. Immunohistochemical localization reveals that EP2 protein is expressed in all cell types of endometrium and myometrium. On d 18, pregnancy up-regulates EP2 protein, primarily in endometrial stroma and myometrial smooth muscle cells. In conclusion, EP2 is the major cAMP-generating PGE₂ receptor expressed and regulated in the bovine uterus during the estrous cycle and early pregnancy.