{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T22:56:11Z","timestamp":1777416971817,"version":"3.51.4"},"reference-count":64,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2015,6,8]],"date-time":"2015-06-08T00:00:00Z","timestamp":1433721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","award":["PG\/11\/11\/28725"],"award-info":[{"award-number":["PG\/11\/11\/28725"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2015,7,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>A correlation was found between <jats:italic>in vivo<\/jats:italic> umbilical artery Doppler velocimetry and resistance to fetal\u2010side flow in the human <jats:italic>ex vivo<\/jats:italic> dually perfused placenta, highlighting that the fetoplacental vascular bed is a key site of resistance to umbilico\u2010placental flow in pregnancy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We discovered high resistance and poor flow\u2010mediated vasodilatory responses in placentas from pregnancies associated with fetal growth restriction (FGR).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Endothelial cells isolated from the FGR placentas and grown in static and flow culture showed a dysregulated phenotype, with biochemical signalling demonstrating a failed compensatory response to high blood\u2010flow resistance.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Increased vascular resistance and reduced fetoplacental blood flow are putative aetiologies in the pathogenesis of fetal growth restriction (FGR); however, the regulating sites and mechanisms remain unclear. We hypothesised that placental vessels dictate fetoplacental resistance and in FGR exhibit endothelial dysfunction and reduced flow\u2010mediated vasodilatation (FMVD). Resistance was measured in normal pregnancies (<jats:italic>n<\/jats:italic>\u00a0=\u00a010) and FGR (<jats:italic>n<\/jats:italic>\u00a0=\u00a010) both <jats:italic>in vivo<\/jats:italic> by umbilical artery Doppler velocimetry and <jats:italic>ex vivo<\/jats:italic> by dual placental perfusion. <jats:italic>Ex vivo<\/jats:italic> FMVD is the reduction in fetal\u2010side inflow hydrostatic pressure (FIHP) following increased flow rate. Results demonstrated a significant correlation between vascular resistance measured <jats:italic>in vivo<\/jats:italic> and <jats:italic>ex vivo<\/jats:italic> in normal pregnancy, but not in FGR. In perfused FGR placentas, vascular resistance was significantly elevated compared to normal placentas (58\u00a0\u00b1\u00a07.7\u00a0mmHg and 36.8\u00a0\u00b1\u00a04.5\u00a0mmHg, respectively; 8\u00a0ml\u00a0min<jats:sup>\u22121<\/jats:sup>; means\u00a0\u00b1\u00a0SEM; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) and FMVD was severely reduced (3.9\u00a0\u00b1\u00a01.3% and 9.1\u00a0\u00b1\u00a01.2%, respectively). In normal pregnancies only, the highest level of <jats:italic>ex vivo<\/jats:italic> FMVD was associated with the lowest <jats:italic>in vivo<\/jats:italic> resistance. Inhibition of NO synthesis during perfusion (100\u00a0\u03bc<jats:sc>m l<\/jats:sc>\u2010NNA) moderately elevated FIHP in the normal group, but substantially in the FGR group. Human placenta artery endothelial cells from FGR groups exhibited increased shear stress\u2010induced NO generation, iNOS expression and eNOS expression compared with normal groups. In conclusion, fetoplacental resistance is determined by placental vessels, and is increased in FGR. The latter also exhibit reduced FMVD, but with a partial compensatory increased NO generation capacity. The data support our hypothesis, which highlights the importance of FMVD regulation in normal and dysfunctional placentation.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp270495","type":"journal-article","created":{"date-parts":[[2015,4,29]],"date-time":"2015-04-29T10:31:03Z","timestamp":1430303463000},"page":"3077-3092","source":"Crossref","is-referenced-by-count":58,"title":["Dysregulated flow\u2010mediated vasodilatation in the human placenta in fetal growth restriction"],"prefix":"10.1113","volume":"593","author":[{"given":"Sarah","family":"Jones","sequence":"first","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, St. Mary's Hospital, Oxford Road  Manchester M13 9WL UK"},{"name":"Maternal and Fetal Health Research Centre, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester M13 9WL UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Bischof","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, St. Mary's Hospital, Oxford Road  Manchester M13 9WL UK"},{"name":"Maternal and Fetal Health Research Centre, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester M13 9WL UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"Lang","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, Histology and Embryology, Medical University of Graz  Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gernot","family":"Desoye","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Graz  Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sue L.","family":"Greenwood","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, St. Mary's Hospital, Oxford Road  Manchester M13 9WL UK"},{"name":"Maternal and Fetal Health Research Centre, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester M13 9WL UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward D.","family":"Johnstone","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, St. Mary's Hospital, Oxford Road  Manchester M13 9WL UK"},{"name":"Maternal and Fetal Health Research Centre, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester M13 9WL UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Wareing","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, St. Mary's Hospital, Oxford Road  Manchester M13 9WL UK"},{"name":"Maternal and Fetal Health Research Centre, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester M13 9WL UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin P.","family":"Sibley","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, St. Mary's Hospital, Oxford Road  Manchester M13 9WL UK"},{"name":"Maternal and Fetal Health Research Centre, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester M13 9WL UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Brownbill","sequence":"additional","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, St. Mary's Hospital, Oxford Road  Manchester M13 9WL UK"},{"name":"Maternal and Fetal Health Research Centre, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester M13 9WL UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,6,8]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1139\/y03-119"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.1880"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2005.082297"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2002.0845"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.310.6981.703"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.298.6673.564"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.OGX.0000133943.54530.76"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115849"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108789200"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2005.08.002"},{"key":"e_1_2_6_12_1","first-page":"305","article-title":"Factors affecting gas transfer across the placenta and the oxygen supply to the fetus","volume":"12","author":"Carter AM","year":"1989","journal-title":"J Dev Physiol"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2009.04.010"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000027813.55750.E7"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2004.03.006"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.01.001"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1159\/000353633"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.4084"},{"issue":"3","key":"e_1_2_6_19_1","first-page":"15","article-title":"New definition of small for gestational age based on fetal growth potential","volume":"65","author":"Gardosi J","year":"2006","journal-title":"Horm Res"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2008.02057.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12274"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1986.tb07935.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2012.02.014"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2014.07.013"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-2115(00)00423-1"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1993.tb15276.x"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.2784"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2012.09.015"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2012.02.006"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.187559"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-0705.1997.10020112.x"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-0436.2008.00302.x"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)71048-5"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1071\/RD9951451"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(96)70432-5"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.103.022293"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.3827"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.14.1.208"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4004(96)80009-9"},{"key":"e_1_2_6_40_1","first-page":"H1730","article-title":"Endothelial vasodilator production by uterine and systemic arteries. II. Pregnancy effects on NO synthase expression","volume":"272","author":"Magness RR","year":"1997","journal-title":"Am J PhysiolHeart CircPhysiol"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20178"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/10601330701274824"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4004(92)90057-Z"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(92)91863-6"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/12.1.167"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.750133"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.4.1970"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0045294"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.5551\/jat.14340"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1997.sp004033"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.104430"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb15111.x"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.25.4.631"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000181381.82856.23"},{"key":"e_1_2_6_55_1","first-page":"R441","article-title":"Nitric oxide and pregnancy","volume":"272","author":"Sladek SM","year":"1997","journal-title":"Am J PhysiolRegulIntegrComp Physiol"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.082832bs"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.5551\/jat.11973"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.1997.5095"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-380864-6.00003-1"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2008.02.008"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.7583"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.001631"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(95)90327-5"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2004.03.005"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.082420"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FJP270495","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FJP270495","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP270495","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP270495","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP270495","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T08:40:19Z","timestamp":1696149619000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP270495"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,8]]},"references-count":64,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2015,7,15]]}},"alternative-id":["10.1113\/JP270495"],"URL":"https:\/\/doi.org\/10.1113\/jp270495","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,8]]}}}