{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:34:31Z","timestamp":1788482071065,"version":"build-2803163510"},"reference-count":80,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T00:00:00Z","timestamp":1586995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD083132"],"award-info":[{"award-number":["HD083132"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Nitric oxide (NO) is a gasotransmitter with important physiological and pathophysiological roles in pregnancy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>There is limited information available about the sources and metabolism of NO and its bioactive metabolites (NOx) in both normal and complicated pregnancies.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The present study characterized and quantified endogenous NOx in human and mouse placenta following determination of the stability of exogenous NOx in placental homogenates.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>NOx have differential stability in placental homogenates. NO and iron nitrosyl species (FeNOs), are relatively unstable in placental homogenates from normal placentas.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Exogenous NO, nitrite and nitrosothiols react with placental homogenates to form iron nitrosyl complexes. FeNOs were also detected endogenously in mouse and human placenta.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>NOx levels in placental villous tissue are increased in fetal growth restriction <jats:italic>vs<\/jats:italic>. placentas from women with normal pregnancies, particularly in fetal growth restriction associated with pre\u2010eclampsia. Villitis was not associated, however, with an increase in NOx levels in either normotensive or pre\u2010eclamptic placentas.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The results call for further investigation of FeNOs in normal and complicated pregnancies.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>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 under conditions of aberrant placental inflammation during pregnancy. An ozone\u2010based chemiluminescence approach was used to investigate 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 pre\u2010eclamptic pregnancies complicated with fetal growth restriction (FGR) with and without villitis of unknown aetiology. We hypothesized that placental NOx would be increased in FGR <jats:italic>vs<\/jats:italic>. normal tissue, and be further increased in villitis <jats:italic>vs<\/jats:italic>. non\u2010villitis 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 <jats:italic>vs<\/jats:italic>. placentas from women with normal pregnancies, particularly in FGR associated with pre\u2010eclampsia. However, in contrast to our hypothesis, villitis was not associated with an increase in NOx levels in either normotensive or pre\u2010eclamptic 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 pre\u2010eclampsia and fetal growth restriction.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp279057","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T11:30:27Z","timestamp":1583148627000},"page":"2223-2241","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Nitric oxide metabolism in the human placenta during aberrant maternal inflammation"],"prefix":"10.1113","volume":"598","author":[{"given":"George T.","family":"Mukosera","sequence":"first","affiliation":[{"name":"Lawrence D Longo Center for Perinatal Biology and Department of Pediatrics Loma Linda University  11175 Campus Street Loma Linda CA 92354 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatianna 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