{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:44:04Z","timestamp":1792205044219,"version":"4.4.0"},"reference-count":57,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:00:00Z","timestamp":1680739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R022690\/1"],"award-info":[{"award-number":["MR\/R022690\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R02524X\/1"],"award-info":[{"award-number":["MR\/R02524X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R022690\/1"],"award-info":[{"award-number":["MR\/R022690\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R02524X\/1"],"award-info":[{"award-number":["MR\/R02524X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality. Altered placental formation and functional capacity are major contributors to FGR pathogenesis. Relating placental structure to function across the placenta in healthy and FGR pregnancies remains largely unexplored but could improve understanding of placental diseases. We investigated integration of these parameters spatially in the term human placenta using predictive modelling. Systematic sampling was able to overcome heterogeneity in placental morphological and molecular features. Defects in villous development, elevated fibrosis, and reduced expression of growth and functional marker genes (IGF2, VEGA, SLC38A1, and SLC2A3) were seen in age-matched term FGR versus healthy control placentas. Characteristic histopathological changes with specific accompanying molecular signatures could be integrated through computational modelling to predict if the placenta came from a healthy or FGR pregnancy. Our findings yield new insights into the spatial relationship between placental structure and function and the etiology of FGR.<\/jats:p>","DOI":"10.3390\/cells12071093","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T08:41:52Z","timestamp":1680770512000},"page":"1093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Integrated Placental Modelling of Histology with Gene Expression to Identify Functional Impact on Fetal Growth"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8814-752X","authenticated-orcid":false,"given":"Hannah Ee Juen","family":"Yong","sequence":"first","affiliation":[{"name":"Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience University of Cambridge, Cambridge CB2 3EG, UK"},{"name":"Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Brenner Centre for Molecular Medicine, Singapore 117609, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Maksym","sequence":"additional","affiliation":[{"name":"Elizabeth Gareth Anderson Institute for Women\u2019s Health, University College London, 84-86 Chenies Mews, London WC1E 6HU, UK"},{"name":"Fetal Medicine Unit Elizabeth Gareth Anderson Wing, University College Hospitals NHS Trust, 25 Grafton Way, London WC1E 6DB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Ashraf Bin","family":"Yusoff","sequence":"additional","affiliation":[{"name":"Elizabeth Gareth Anderson Institute for Women\u2019s Health, University College London, 84-86 Chenies Mews, London WC1E 6HU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Salazar-Petres","sequence":"additional","affiliation":[{"name":"Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience University of Cambridge, Cambridge CB2 3EG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4245-7346","authenticated-orcid":false,"given":"Tatiana","family":"Nazarenko","sequence":"additional","affiliation":[{"name":"Elizabeth Gareth Anderson Institute for Women\u2019s Health, University College London, 84-86 Chenies Mews, London WC1E 6HU, UK"},{"name":"Department of Mathematics, University College London, London WC1E 6AE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Zaikin","sequence":"additional","affiliation":[{"name":"Elizabeth Gareth Anderson Institute for Women\u2019s Health, University College London, 84-86 Chenies Mews, London WC1E 6HU, UK"},{"name":"Department of Mathematics, University College London, London WC1E 6AE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0199-6140","authenticated-orcid":false,"given":"Anna L.","family":"David","sequence":"additional","affiliation":[{"name":"Elizabeth Gareth Anderson Institute for Women\u2019s Health, University College London, 84-86 Chenies Mews, London WC1E 6HU, UK"},{"name":"Fetal Medicine Unit Elizabeth Gareth Anderson Wing, University College Hospitals NHS Trust, 25 Grafton Way, London WC1E 6DB, UK"},{"name":"National Institute for Health Research University College London Hospitals Biomedical Research Centre, 149 Tottenham Court Road, London W1T 7DN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2971-6865","authenticated-orcid":false,"given":"Sara L.","family":"Hillman","sequence":"additional","affiliation":[{"name":"Elizabeth Gareth Anderson Institute for Women\u2019s Health, University College London, 84-86 Chenies Mews, London WC1E 6HU, UK"},{"name":"Fetal Medicine Unit Elizabeth Gareth Anderson Wing, University College Hospitals NHS Trust, 25 Grafton Way, London WC1E 6DB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4931-4233","authenticated-orcid":false,"given":"Amanda N.","family":"Sferruzzi-Perri","sequence":"additional","affiliation":[{"name":"Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience University of Cambridge, Cambridge CB2 3EG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3389\/fphys.2018.01091","article-title":"The role of placental hormones in mediating maternal adaptations to support pregnancy and lactation","volume":"9","author":"Napso","year":"2018","journal-title":"Front. 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