Trophoblast plugs: impact on utero-placental haemodynamics and spiral artery remodelling.

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dc.contributor.author James, Joanna en
dc.contributor.author Saghian, Rojan en
dc.contributor.author Perwick, Rebecca en
dc.contributor.author Clark, Alys en
dc.date.accessioned 2018-12-06T01:50:15Z en
dc.date.issued 2018-08 en
dc.identifier.issn 0268-1161 en
dc.identifier.uri http://hdl.handle.net/2292/44889 en
dc.description.abstract STUDY QUESTION:How does trophoblast plugging impact utero-placental haemodynamics? SUMMARY ANSWER:Physiological trophoblast plug structures are dense enough to restrict flow of oxygenated blood to the intervillous space (IVS) in the first trimester, and result in a shear stress environment upstream of the plugs that promotes spiral artery remodelling. WHAT IS KNOWN ALREADY:Trophoblast plugging of the uterine spiral arteries is thought to be the dominant factor restricting the flow of oxygenated maternal blood to the placenta in the first trimester of pregnancy. However, the extent of plugging, the timing of plug break up, and the impact of plug structure on pregnancy outcomes is debated. STUDY DESIGN, SIZE, DURATION:A computational model of the uterine radial and spiral arteries, incorporating arteriovenous anastomoses was developed. The model was parameterized with our own histological data and previous literature descriptions of the dimensions of the spiral arteries, and the structural properties (porosity) of trophoblast plugs. PARTICIPANTS/MATERIALS, SETTING, METHODS:Structural data were acquired from the literature, and supplemented by images of the spiral arteries acquired by standard thin-section 2D immunohistochemistry, and whole mount immunohistochemistry imaged in 3D by micro-CT. Computational models were solved using Matlab software, via custom written scripts. MAIN RESULTS AND THE ROLE OF CHANCE:We confirm that physiological lengths (>0.1 mm) and porosities (0.2-0.6) of trophoblast plugs are sufficient to restrict the flow of oxygenated maternal blood flow to the placental surface. Trophoblast plugs also have important haemodynamic consequences upstream in the spiral arteries by generating shear stress conditions of <2 dyne/cm2 that promote trophoblast-induced spiral artery remodelling. Structural changes in plugs as they dislodge are likely to result in rapid increases in blood flow to the IVS, and it is likely at this stage of gestation that the major source of resistance in the utero-placental circulation transitions from the spiral arteries to the radial arteries, which then act as a the 'rate-limiting' step to IVS flow. LIMITATIONS, REASONS FOR CAUTION:Structural descriptions of the spiral arteries, radial arteries and trophoblast plugs largely rely on 2D histological sections, or historical measurements. Increased focus on quantitatively assessing the 3D structure of the uterine arteries using more modern imaging technologies in the future will strengthen model predictions. WIDER IMPLICATIONS OF THE FINDINGS:Our work suggests that trophoblast plugs play a previously under-appreciated role in regulating spiral artery remodelling in the first trimester of human pregnancy. This creates the possibility that inadequate trophoblast plugging in the first trimester may contribute to the inadequate artery remodelling observed in pregnancy pathologies such as pre-eclampsia. The incorporation of arteriovenous anastomoses in our model highlights the important influence that shunted blood can play in utero-placental haemodynamics, and together with the emerging role of radial arteries in regulating blood flow to the placenta, the influence of arteriovenous anastomoses on radial artery haemodynamics in normal and pathological pregnancies warrants further investigation. STUDY FUNDING/COMPETING INTEREST(S):This research was supported by a Royal Society of New Zealand Marsden Fund award (13-UOA-032). A.R.C. is supported by a Royal Society of New Zealand Rutherford Discovery Fellowship (14-UOA-019). R.S. was supported by a Gravida (National Centre for Growth and Development) postgraduate scholarship. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER:N/A. en
dc.format.medium Print en
dc.language eng en
dc.relation.ispartofseries Human reproduction (Oxford, England) en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.subject Trophoblasts en
dc.subject Placenta en
dc.subject Humans en
dc.subject Oxygen en
dc.subject Capillary Permeability en
dc.subject Pregnancy en
dc.subject Pregnancy Trimester, First en
dc.subject Placental Circulation en
dc.subject Regional Blood Flow en
dc.subject Porosity en
dc.subject Models, Cardiovascular en
dc.subject Female en
dc.subject Hemodynamics en
dc.subject X-Ray Microtomography en
dc.subject Uterine Artery en
dc.subject Patient-Specific Modeling en
dc.subject Vascular Remodeling en
dc.subject Computed Tomography Angiography en
dc.title Trophoblast plugs: impact on utero-placental haemodynamics and spiral artery remodelling. en
dc.type Journal Article en
dc.identifier.doi 10.1093/humrep/dey225 en
pubs.issue 8 en
pubs.begin-page 1430 en
pubs.volume 33 en
dc.rights.holder Copyright: The author en
pubs.end-page 1441 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Video-Audio Media en
pubs.subtype Journal Article en
pubs.elements-id 750045 en
pubs.org-id Bioengineering Institute en
pubs.org-id ABI Associates en
pubs.org-id Medical and Health Sciences en
pubs.org-id School of Medicine en
pubs.org-id Obstetrics and Gynaecology en
dc.identifier.eissn 1460-2350 en
pubs.record-created-at-source-date 2018-06-30 en
pubs.dimensions-id 29955830 en


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