• Nitric Oxide Metabolism in the Human Placenta during Aberrant Maternal Inflammation Nitric oxide (NO) is a gasotransmitter with important roles in pregnancy under both physiological and pathophysiological conditions. Although products of NO metabolism (NOx) also have significant bioactivity, little is known about the role of NO and NOx in conditions of aberrant placental inflammation during pregnancy. An ozone-based chemiluminescence approach was used to study the stability and metabolic fate of NOx in human placental homogenates from uncomplicated pregnancies in healthy mothers compared to that in placental tissue from normotensive and preeclamptic pregnancies complicated with fetal growth restriction (FGR) with and without villitis of unknown etiology. We hypothesized that placental NOx would be increased in FGR versus normal tissue, and further increased in villitis versus non-villitis placentas. Findings indicate that nitrate, nitrite, and nitrosothiols, but not NO or iron nitrosyl species (FeNOs), are relatively stable in placental homogenates from normal placentas, and that NO, nitrite and nitrosothiols react with placental homogenates to form iron nitrosyl complexes. Furthermore, NOx levels in placental villous tissue are increased in FGR versus placentas from women with normal pregnancies, particularly in FGR associated with preeclampsia. However, contrary to our hypothesis, villitis was not associated with an increase in NOx levels in either normotensive or preeclamptic placentas. Our results also strongly support the involvement of FeNOs in both mouse and human placenta, and call for their further study as a critical mechanistic link between preeclampsia and fetal growth restriction. (03/2020) (link)