Expression of cyclooxygenase‐2 in embryonic and fetal tissues during organogenesis and late pregnancy

Abstract

Cyclooxygenase (COX) catalyzes the committed step in prostaglandin biosynthesis and exists as two related but unique isoforms, COX-1 (constitutive) and COX-2 (inducible). Prostaglandins (PGs) are known to have many important functions in reproduction, such as placentation and decidualization. Studies with the COX-1 and COX-2 knockout mice have demonstrated that COX-2, but not COX-1, is crucial for normal ovulation, implantation, and decidualization, suggesting that COX-2–derived PGs are important during the initial stages of pregnancy. Although the COX-2 knockout mice did not exhibit any abnormalities at birth, relatively little information exists with regard to the expression of COX-2 in the fetus during development. In order to understand the role of COX-2 throughout pregnancy, we characterized the cell type and the temporal expression of inducible COX-2 throughout embryonic and fetal development in the rat (n = 22) by immunohistochemistry and in situ hybridization. High levels of COX-2 expression were seen in decidualized uterine tissue on gestation days 7–13 and then in the fetal membranes on gestation days 17–20. Cyclooxygenase-2 expression was not detectable in any tissues from developing embryos during gestation days 7–13, but was observed in the fetal growth period (gestation days 15–20) in the skin, heart, cartilage, and the kidney. No COX-2 expression was seen in fetal tissues at days 7–13 of gestation, but was seen in various tissues at days 15–17 of gestation. These observations suggest that COX-2 may be important in mid to late pregnancy through an effect on fetal organ growth, but not in the organogenetic phase of fetal development. Birth Defects Research (Part A) 67:54–58, 2003.