Cyclooxygenase-2 expression in the developing human kidney

Cyclooxygenase (COX) exists in two related but unique isoforms, COX-1 and C OX-2, and is suggested to have specific functions in different segments of the nephron. COX-2 knockout mice develop fatal nephropathy, which implies t hat this isoform is important during nephrogenesis. The histologic changes seen in the COX-2 knockout mice are similar to those observed in the kidney s of human fetuses exposed to non-steroidal anti-inflammatory drugs (NSAIDs ) in the third trimester of pregnancy. However, only minimal amounts of COX -2 mRNA or protein have been reported in the adult human kidney. We hypothe sized that expression of COX-2 is significant in the fetal human kidney and that it is involved in the development of the nephron. To characterize the presence of COX-2 in the human fetal kidney, we used immunohistochemistry to evaluate its expression in 23 fetal kidneys ranging between 15 and 23 we eks of gestational age. Strong expression of COX-2 was localized primarily in the macula densa and the thick ascending limb of the loop of Henle, and in rare glomerular podocytes and vascular endothelial cells. There was a pr ogressive decrease in COX-2 immunoreactivity from the most immature nephron s adjacent to the metanephric regions to the well-developed nephrons in the middle to inner cortex. In contrast to the adult human kidney, this tempor al and spatial expression of COX-2 in the fetal kidney suggests that this e nzyme may be involved in nephrogenesis, and its inhibition by NSAlDs during the third trimester may be responsible for fetal renal syndromes.