Temporal and tissue-specific expression of prostaglandin receptors EP2, EP3, EP4, FP, and cyclooxygenases 1 and 2 in uterus and fetal membranes during bovine pregnancy

Uteroplacental prostaglandins (PGs) play pivotal roles in maintenance and / or termination of pregnancy in mammals. Regulation of PG biosynthetic and signaling mechanisms in uteroplacental tissues during maintenance of pregnancy is largely unknown. In the present study, we have characterized the expression of PGE(2) receptors (EP2, EP3, EP4), PGF(2alpha) receptor (FP), and cyclooxygenase (COX) types 1 and 2 in placentome caruncle (CAR), intercaruncle, and fetal membrane tissues during pregnancy in cattle. Pregnant bovine uteri were collected and classified into six groups covering the entire gestational length. The levels of expression of EP2, EP3, and FP mRNAs differ depending on tissues and days of gestation (days < 50 to > 250). EP4 mRNA was undetectable in all the tissues studied. The expression levels of PG receptor mRNAs were as follows: placentome CAR FP > EP2 > EP3, intercaruncle EP2 > EP3 greater than or equal to FP, and fetal membranes EP3 greater than or equal to EP2 >> FP. EP2 and EP3 expressions were modulated in uteroplacental tissues, depending on days of pregnancy, whereas FP was uniformly expressed. COX-1 mRNA and protein were constitutively expressed, whereas COX-2 was highly modulated in uteroplacental tissues throughout pregnancy. Immunohistochemistry showed that EP2 and COX-2 proteins were colocalized in most cell types of placentome CAR, endometrium, and myometrium. Our study indicates that EP2 is the primary cAMP-generating PGE(2) receptor expressed in uteroplacental tissues during bovine pregnancy. Temporal and tissue-specific expression of PGE(2) and PGF(2alpha) receptors and COX-1 and -2 at the maternal-fetal interface suggests a selective and distinctive role for PGE(2) and PGF(2alpha) in uterine activities during pregnancy in bovine.