Expression of nitric oxide synthase by syncytiotrophoblast in human placental villi.

The endogenous biosynthesis of nitric oxide (NO) is increased during gestation. To begin our investigation of a possible tissue source (or sources), we examined the placenta. We postulated that analogous to the endothelium of blood vessels, the syncytiotrophoblast (STr) cell layer that lines the intervillous blood space of the human placenta would express NO synthase. Our results show that human placental villi express a calcium- and calmodulin-sensitive form of NO synthase, located mainly in the microsomal cell fraction. By in situ hybridization using a riboprobe generated from human endothelial NO synthase cDNA, we observe NO synthase mRNA expression in STr. The STr also shows NADPH-diaphorase staining, indicating the presence of NO synthase, and most likely other flavin-containing enzymes involved in sex steroid metabolism. NO synthase activity was also detected in the villi of a complete mole placenta (which lacks fetal vessels), further supporting a trophoblastic origin. Our findings suggest a previously unrecognized role for STr-derived NO in placental function.