{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:35:26Z","timestamp":1790501726784,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fetal growth restriction (FGR) is a pregnancy complication wherein the foetus fails to reach its growth potential. The renin\u2013angiotensin system (RAS) is a critical regulator of placental function, controlling trophoblast proliferation, angiogenesis and blood flow. The RAS significantly influences uteroplacental blood flow through the balance of its vasoconstrictive and vasodilatory pathways. Although the RAS is known to be dysregulated in placentae from women with preeclampsia, the expression of the RAS has not yet been studied in pregnancies compromised by FGR alone. This study investigated the mRNA expression and protein levels of RAS components in placentae from pregnancies compromised by FGR. Angiotensin II type 1 receptor (AGTR1) and angiotensin-converting enzyme 2 (ACE2) mRNA levels were reduced in FGR placentae compared with control (P\u2009=\u20090.012 and 0.018 respectively). Neprilysin (NEP) mRNA expression was lower in FGR placentae compared with control (P\u2009=\u20090.004). mRNA levels of angiotensinogen (AGT) tended to be higher in FGR placentae compared with control (P\u2009=\u20090.090). Expression of prorenin, AGT, angiotensin-converting enzyme (ACE) or ACE2 proteins were similar in control and FGR placentae. The renin-AGT reaction is a first order reaction so levels of expression of placental AGT determine levels of Ang II. Decreasing levels of ACE2 and\/or NEP by limiting the production of Ang-(1-7), which is a vasodilator, and increasing placental Ang II levels (vasoconstrictor) may result in an imbalance between the vasoconstrictor and vasodilator arms of the placental RAS. Ultimately this dysregulation of the placental RAS could lead to reduced placental perfusion that is evident in FGR.<\/jats:p>","DOI":"10.1530\/rep-18-0633","type":"journal-article","created":{"date-parts":[[2019,6,18]],"date-time":"2019-06-18T11:58:44Z","timestamp":1560859124000},"page":"237-245","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":47,"title":["Dysregulation of the placental renin\u2013angiotensin system in human fetal growth restriction"],"prefix":"10.1093","volume":"158","author":[{"given":"Sarah J","family":"Delforce","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy , University of Newcastle, Newcastle, New South Wales, Australia"},{"name":"Priority Research Centre for Reproductive Sciences , University of Newcastle, Newcastle, New South Wales, Australia"},{"name":"Hunter Medical Research Institute , Newcastle, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenie R","family":"Lumbers","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy , University of Newcastle, Newcastle, New South Wales, Australia"},{"name":"Priority Research Centre for Reproductive Sciences , University of Newcastle, Newcastle, New South Wales, Australia"},{"name":"Hunter Medical Research Institute , Newcastle, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey J","family":"Ellery","sequence":"additional","affiliation":[{"name":"The Ritchie Centre , Hudson Institute of Medical Research, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padma","family":"Murthi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology , Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia"},{"name":"Department of Maternal-Fetal Medicine , Pregnancy Research Centre, Royal Women\u2019s Hospital, Parkville, Victoria, Australia"},{"name":"Department of Obstetrics & Gynaecology , University of Melbourne, Parkville, Victoria, Australia"},{"name":"The Ritchie Centre , Hudson Institute of Medical Research, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsty G","family":"Pringle","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy , University of Newcastle, Newcastle, New South Wales, Australia"},{"name":"Priority Research Centre for Reproductive Sciences , University of Newcastle, Newcastle, New South Wales, Australia"},{"name":"Hunter Medical Research Institute , Newcastle, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,9,1]]},"reference":[{"key":"2026010712243919700_bib1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.103861","article-title":"Activation of local chorionic villi angiotensin II levels but not angiotensin (1\u20137) in preeclampsia","volume":"51","author":"Anton","year":"2008","journal-title":"Hypertension"},{"key":"2026010712243919700_bib2","doi-asserted-by":"publisher","DOI":"10.1136\/jech.58.2.114","article-title":"Developmental origins of adult health and disease","volume":"58","author":"Barker","year":"2004","journal-title":"Journal of Epidemiology and Community Health"},{"key":"2026010712243919700_bib3","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2002.125243","article-title":"Decreased vascularization and cell proliferation in placentas of intrauterine growth-restricted fetuses with abnormal umbilical artery flow velocity waveforms","volume":"187","author":"Chen","year":"2002","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"2026010712243919700_bib4","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-018-1455-2","article-title":"Measurement of the total angiotensinogen and its reduced and oxidised forms in human plasma using targeted LC-MS\/MS","volume":"411","author":"Dahabiyeh","year":"2019","journal-title":"Analytical and Bioanalytical Chemistry"},{"key":"2026010712243919700_bib5","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199816121-00005","article-title":"Angiotensinogen (M235T) and angiotensin-converting enzyme (I\/D) polymorphisms in association with plasma renin and prorenin levels","volume":"16","author":"Danser","year":"1998","journal-title":"Journal of Hypertension"},{"key":"2026010712243919700_bib6","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2017.03.007","article-title":"Regulation of the prorenin \u2013 angiotensin system by oxygen and miRNAs; 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