3D Microscopic Morphology of the Human Placental Villous Tree at Birth in Health and Disease

• Applicants: Dr. Nirav Barapatre; Professor Dr. Hans-Georg Frank
• Subject Area: Reproductive Medicine, Urology ; Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2017 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 387763697

• Final Report Year: 2024

Final Report Abstract

This project explores the structural and functional changes in the placental villous tree associated with major obstetric syndromes: Fetal Growth Restriction (FGR), Preeclampsia (PE), and Gestational Diabetes Mellitus (GDM). Using advanced 3D morphometric and imaging techniques, it highlights the role of the villous tree, a central structure at the materno-fetal interface, in the pathophysiology of these syndromes. Findings demonstrate that FGR is characterised by reduced placental weight due to diminished volume in central villi, while PE primarily exhibits maternal symptoms and structural dimorphism in the villous trophoblast. In GDM, despite well-controlled hyperglycaemia, subtle alterations in villous branching suggest functional impairments. Across conditions, sexual dimorphism was identified, with distinct trophoblast proliferation patterns between male and female placentas. The project also developed innovative imaging methods, such as µCT with enhanced contrast techniques, enabling detailed analyses of villous structures. These findings correlate 3D morphological changes with clinical outcomes, providing insights into placental function and pathology. The study advances understanding of the placental role in pregnancy complications and offers potential for therapeutic strategies, including computational blood flow modelling and improved diagnostic methodologies.

Publications

• Dynamic modeling of uteroplacental blood flow in IUGR indicates vortices and elevated pressure in the intervillous space – a pilot study. Scientific Reports, 7(1).
  Roth, Christian J.; Haeussner, Eva; Ruebelmann, Tanja; Koch, Franz v.; Schmitz, Christoph; Frank, Hans-Georg & Wall, Wolfgang A.
  
• Syncytial nuclei accumulate at the villous surface in IUGR while proliferation is unchanged. Placenta, 60, 47-53.
  Haeussner, E.; Schmitz, C.; Grynspan, D.; Edler von Koch, F. & Frank, H.-G.
  
• Placental Morphology Is Associated with Maternal Depressive Symptoms during Pregnancy and Toddler Psychiatric Problems. Scientific Reports, 8(1).
  Lahti-Pulkkinen, Marius; Cudmore, Melissa Jane; Haeussner, Eva; Schmitz, Christoph; Pesonen, Anu-Katriina; Hämäläinen, Esa; Villa, Pia M.; Mehtälä, Susanna; Kajantie, Eero; Laivuori, Hannele; Reynolds, Rebecca M.; Frank, Hans-Georg & Räikkönen, Katri
  
• Stereologische Volumenbestimmung immunhistochemisch differenzierter Strukturbestandteile ¨ der menschlichen Plazenta. PhDthesis, Munchen, 2018.
  Antonia Buhlmeyer
  
• The Density of Cell Nuclei at the Materno-Fetal Exchange Barrier is Sexually Dimorphic in Normal Placentas, but not in IUGR. Scientific Reports, 9(1).
  Barapatre, Nirav; Haeussner, Eva; Grynspan, David; Schmitz, Christoph; Edler von Koch, Franz & Frank, Hans-Georg
  
• The volume of villi with γ-sm-actin positive perivascular cells correlates with placental weight and thickness. Placenta, 85, 24-31.
  Buehlmeyer, A.; Barapatre, N.; Schmitz, C.; Edler von Koch, F.; Haeussner, E. & Frank, H.-G.
  
• Air contrast of the intervillous space enables non-disruptive Micro-CT analysis of paraffin-embedded archival placental tissue. Placenta, 100, 66-68.
  Barapatre, N.; Aschauer, B.; Kampfer, C.; Schmitz, C.; von Koch, F.E. & Frank, H.-G.
  
• Growth restricted placentas show severely reduced volume of villous components with perivascular myofibroblasts. Placenta, 109, 19-27.
  Barapatre, Nirav; Kampfer, Cornelia; Henschen, Sina; Schmitz, Christoph; Edler von Koch, Franz & Frank, Hans-Georg
  
• Stereologische Untersuchung immunhistochemisch differenzierter Strukturbestandteile des Zottenbaums menschlicher Plazenten mit und ohne IUGR. PhDthesis, Munchen, 2022.
  Sina Henschen
  
• Die Mikroarchitektur der humanen Plazenta und ihre Korrelation mit dem Plazentagewicht in physiologischen Schwangerschaften PhDthesis, Munchen, 2023.
  Katharina Renz
  
• Fibroblast activating protein (FAP) is reduced in FGR in regions of the villous tree with disturbed differentiation of perivascular myofibroblasts. Placenta, 140, e49.
  Kampfer, Cornelia; Barapatre, Nirav; Schmitz, Christoph; Edler von Koch, Franz & Frank, Hans-Georg
  
• From a single villous tree to whole placentome – quantitative imaging of the placental villous architecture by Micro-CT. Placenta, 140, e65.
  Barapatre, Nirav; Achterhold, Klaus; Kampfer, Cornelia; Rübelmann, Tanja; Edler von Koch, Franz; Pfeiffer, Franz; Schmitz, Christoph & Frank, Hans-Georg
  
• Fluid flow patterns in the intervillous space of a scaled, 3D-printed, human placental cotyledon as visualized by high-resolution MRI. Placenta, 154, e32.
  Barapatre, Nirav; Frank, David; Achterhold, Klaus; Pfeiffer, Franz; Edler von Koch, Franz; Grundmann, Sven; Frank, Hans-Georg & Bruschewski, Martin
  
• Investigating Villous Tree Alterations in Gestational Diabetes: Beyond Macrosomia. Placenta, 154, e32.
  Halm, Lea; Schmitz, Christoph; Edler, v. Koch Franz; Frank, Hans-Georg & Barapatre, Nirav
  
• Trophoblast proliferation is higher in female than in male preeclamptic placentas. Placenta, 158, 310-317.
  Barapatre, N.; Hansen, L.; Kampfer, C.; Rübelmann, T.; Schmitz, C.; von Koch, F. & Frank, H.G.