Three-Dimensional Histological Characterization of the Placental Vasculature Using Light Sheet Microscopy
Lennart Freise,
Rose Yinghan Behncke,
Hanna Helene Allerkamp,
Tim Henrik Sandermann,
Ngoc Hai Chu,
Eva Maria Funk,
Lukas Jonathan Hondrich,
Alina Riedel,
Christian Witzel,
Nils Rouven Hansmeier,
Magdalena Danyel,
Alexandra Gellhaus,
Ralf Dechend,
René Hägerling
Affiliations
Lennart Freise
Research Group ‘Lymphovascular Medicine and Translational 3D-Histopathology’, Institute of Medical and Human Genetics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
Rose Yinghan Behncke
Research Group ‘Lymphovascular Medicine and Translational 3D-Histopathology’, Institute of Medical and Human Genetics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
Hanna Helene Allerkamp
Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria
Tim Henrik Sandermann
Research Group ‘Lymphovascular Medicine and Translational 3D-Histopathology’, Institute of Medical and Human Genetics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
Ngoc Hai Chu
Research Group ‘Lymphovascular Medicine and Translational 3D-Histopathology’, Institute of Medical and Human Genetics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
Eva Maria Funk
Research Group ‘Lymphovascular Medicine and Translational 3D-Histopathology’, Institute of Medical and Human Genetics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
Lukas Jonathan Hondrich
Research Group ‘Lymphovascular Medicine and Translational 3D-Histopathology’, Institute of Medical and Human Genetics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
Alina Riedel
Department of Gynecology and Obstetrics, University Hospital Essen, 45147 Essen, Germany
Christian Witzel
Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
Nils Rouven Hansmeier
Research Group ‘Lymphovascular Medicine and Translational 3D-Histopathology’, Institute of Medical and Human Genetics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
Magdalena Danyel
Research Group ‘Lymphovascular Medicine and Translational 3D-Histopathology’, Institute of Medical and Human Genetics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
Alexandra Gellhaus
Department of Gynecology and Obstetrics, University Hospital Essen, 45147 Essen, Germany
Ralf Dechend
Experimental and Clinical Research Center (ECRC), a Cooperation of Charité - Universitätsmedizin Berlin and Max Delbruck Center for Molecular Medicine (MDC), Lindenbergerweg 80, 13125 Berlin, Germany
René Hägerling
Research Group ‘Lymphovascular Medicine and Translational 3D-Histopathology’, Institute of Medical and Human Genetics, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
The placenta is the first embryonic organ, representing the connection between the embryo and the mother, and is therefore necessary for the embryo’s 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.