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