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 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 387763697

The human placenta is key to success of pregnancy and is involved in obstetrical syndromes like intrauterine growth restriction, preeclampsia, and gestational diabetes mellitus. Disturbed placental function is a central axis by which, potentially lifelong health risks (e.g. with regard to the so-called metabolic syndrome) can be caused in the offspring. This phenomenon is known as developmental programming. Epidemiological analysis of developmental programming so far has mainly relied on gross anatomic placental measures like weight and thickness of placentas. Microscopic correlates of these gross anatomic parameteres were not known. During the first phase of this project, novel 3D microscopic approaches were able to identify microscopic structures, which correlate with placental weight and thickness. These structures are special villi of the placental villous tree which are contractile along their longitudinal axis. Intrauterine growth restriction is an obstetric syndrome which is characterized by reduced placental weight and reduced fetal weight. The same 3D microscopic procedures showed that the pathologically reduced placental weight in this syndrome is also correlated with reduced occurrence of these contractile villi. With the 3D microscopic methods established in the first phase of the project, we can use archived material, embedded in paraffin. We have systematically enlarged our tissue archives and will now address the other obstetric syndromes, mainly preeclampsia and gestational diabetes mellitus. A timeline of placental development will also be established during this second phase of the project. While these efforts will be applications of the newly established methods, we will also aim at improvements and further development of the new approaches. Special focus will be given to microCT as a novel imaging approach and to automatisation of 3D microscopic analysis. In this context, we will extend the 3D microscopic methods to the analysis of intravillous capillary networks. The contractile cells (myofibroblasts) of the longitudinally contractile villi will be qualitatively analysed by immunohistochemical methods in order to identify their origin, differentiation and potentially also migration in the placental villous tree.

• DFG Programme: Research Grants