{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:59:42Z","timestamp":1789023582447,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,17]],"date-time":"2023-06-17T00:00:00Z","timestamp":1686960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Berlin Institute of Health (BIH)","award":["491780329"],"award-info":[{"award-number":["491780329"]}]},{"name":"Berlin Institute of Health (BIH)","award":["GE2223\/2-1"],"award-info":[{"award-number":["GE2223\/2-1"]}]},{"name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin and the Berlin Institute of Health","award":["491780329"],"award-info":[{"award-number":["491780329"]}]},{"name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin and the Berlin Institute of Health","award":["GE2223\/2-1"],"award-info":[{"award-number":["GE2223\/2-1"]}]},{"name":"German Research Foundation (DFG)","award":["491780329"],"award-info":[{"award-number":["491780329"]}]},{"name":"German Research Foundation (DFG)","award":["GE2223\/2-1"],"award-info":[{"award-number":["GE2223\/2-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The placenta is the first embryonic organ, representing the connection between the embryo and the mother, and is therefore necessary for the embryo\u2019s growth and survival. To meet the ever-growing need for nutrient and gas exchange, the maternal spiral arteries undergo extensive remodeling, thus increasing the uteroplacental blood flow by 16-fold. However, the insufficient remodeling of the spiral arteries can lead to severe pregnancy-associated disorders, including but not limited to pre-eclampsia. Insufficient endovascular trophoblast invasion plays a key role in the manifestation of pre-eclampsia; however, the underlying processes are complex and still unknown. Classical histopathology is based on two-dimensional section microscopy, which lacks a volumetric representation of the vascular remodeling process. To further characterize the uteroplacental vascularization, a detailed, non-destructive, and subcellular visualization is beneficial. In this study, we use light sheet microscopy for optical sectioning, thus establishing a method to obtain a three-dimensional visualization of the vascular system in the placenta. By introducing a volumetric visualization method of the placenta, we could establish a powerful tool to deeply investigate the heterogeneity of the spiral arteries during the remodeling process, evaluate the state-of-the-art treatment options, effects on vascularization, and, ultimately, reveal new insights into the underlying pathology of pre-eclampsia.<\/jats:p>","DOI":"10.3390\/biom13061009","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T01:31:14Z","timestamp":1687138274000},"page":"1009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Three-Dimensional Histological Characterization of the Placental Vasculature Using Light Sheet Microscopy"],"prefix":"10.3390","volume":"13","author":[{"given":"Lennart","family":"Freise","sequence":"first","affiliation":[{"name":"Research Group \u2018Lymphovascular Medicine and Translational 3D-Histopathology\u2019, Institute of Medical and Human Genetics, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, BIH Center for Regenerative Therapies, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8503-3411","authenticated-orcid":false,"given":"Rose Yinghan","family":"Behncke","sequence":"additional","affiliation":[{"name":"Research Group \u2018Lymphovascular Medicine and Translational 3D-Histopathology\u2019, Institute of Medical and Human Genetics, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, BIH Center for Regenerative Therapies, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4789-9730","authenticated-orcid":false,"given":"Hanna Helene","family":"Allerkamp","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim Henrik","family":"Sandermann","sequence":"additional","affiliation":[{"name":"Research Group \u2018Lymphovascular Medicine and Translational 3D-Histopathology\u2019, Institute of Medical and Human Genetics, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, BIH Center for Regenerative Therapies, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc Hai","family":"Chu","sequence":"additional","affiliation":[{"name":"Research Group \u2018Lymphovascular Medicine and Translational 3D-Histopathology\u2019, Institute of Medical and Human Genetics, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, BIH Center for Regenerative Therapies, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3376-259X","authenticated-orcid":false,"given":"Eva Maria","family":"Funk","sequence":"additional","affiliation":[{"name":"Research Group \u2018Lymphovascular Medicine and Translational 3D-Histopathology\u2019, Institute of Medical and Human Genetics, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, BIH Center for Regenerative Therapies, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas Jonathan","family":"Hondrich","sequence":"additional","affiliation":[{"name":"Research Group \u2018Lymphovascular Medicine and Translational 3D-Histopathology\u2019, Institute of Medical and Human Genetics, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, BIH Center for Regenerative Therapies, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3404-2573","authenticated-orcid":false,"given":"Alina","family":"Riedel","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Witzel","sequence":"additional","affiliation":[{"name":"Department of Surgery, Campus Charit\u00e9 Mitte and Campus Virchow-Klinikum, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7024-5351","authenticated-orcid":false,"given":"Nils Rouven","family":"Hansmeier","sequence":"additional","affiliation":[{"name":"Research Group \u2018Lymphovascular Medicine and Translational 3D-Histopathology\u2019, Institute of Medical and Human Genetics, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, BIH Center for Regenerative Therapies, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"Research Group \u2018Development and Disease\u2019, Max Planck Institute for Molecular Genetics, Ihnestra\u00dfe 63\u201373, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Danyel","sequence":"additional","affiliation":[{"name":"Research Group \u2018Lymphovascular Medicine and Translational 3D-Histopathology\u2019, Institute of Medical and Human Genetics, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, BIH Academy, Clinician Scientist Program, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9506-4581","authenticated-orcid":false,"given":"Alexandra","family":"Gellhaus","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Dechend","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC), a Cooperation of Charit\u00e9 - Universit\u00e4tsmedizin Berlin and Max Delbruck Center for Molecular Medicine (MDC), Lindenbergerweg 80, 13125 Berlin, Germany"},{"name":"HELIOS Klinikum, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6830-2043","authenticated-orcid":false,"given":"Ren\u00e9","family":"H\u00e4gerling","sequence":"additional","affiliation":[{"name":"Research Group \u2018Lymphovascular Medicine and Translational 3D-Histopathology\u2019, Institute of Medical and Human Genetics, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, BIH Center for Regenerative Therapies, Augustenburger Platz 1, 13353 Berlin, Germany"},{"name":"Research Group \u2018Development and Disease\u2019, Max Planck Institute for Molecular Genetics, Ihnestra\u00dfe 63\u201373, 14195 Berlin, Germany"},{"name":"Berlin Institute of Health, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, BIH Academy, Clinician Scientist Program, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1093\/biolre\/ioy049","article-title":"Hemochorial placentation: Development, function, and adaptations","volume":"99","author":"Soares","year":"2018","journal-title":"Biol. 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