Keywords:human placenta, dual placental perfusion system, PlaZentaTox, materno-fetal lipid axis, (patho)physiology of the placenta, neonatal lipoproteins, bioactive lipids and enzymes, inflammatory disorders in pregnancy
Research interest:The laboratory is carrying out research on the molecular mechanisms of the human placenta responsible for pregnancy diseases associated with inflammation such as gestational diabetes or pre-eclampsia. A longstanding and central interest has been on the role of lipid and lipoprotein transfer across the human placenta. Importantly, the transport of bioactive lipids and fatty acids from the mother to fetus across the placental barrier has long been neglected. We are investigating by running ex vivo placental perfusion experiments together with in vitro cell culture assays if and how bioactive lipids and lipoproteins may cross the different biological barriers of the human term placenta.
Another research line is focusing on the composition and functionality of neonatal high-density lipoprotein
(HDL) in order to understand its role on the feto-placental endothelium and its impact on barrier function
in normal and pathophysiological pregnancies (1, 2). Emerging
evidence suggests that HDL function is not always accurately predicted by HDL cholesterol levels. The
functions of HDL include reverse cholesterol transport and modulation of inflammation. These functions appear
to have evolved as part of the innate immune system. In healthy individuals, in the absence of systemic
oxidative stress and inflammation, HDL is anti-inflammatory. However, in those with chronic illnesses such as
diabetes that are characterized by systemic oxidative stress and inflammation, HDL may actually promote the
inflammatory response (
The laboratory is also investigating the mechanisms how nanoparticles (NP) interact with the different placental barriers. This project focuses on NP passage through the maternal-fetal junction by analyzing the structure and functions of the human placental barrier and transfer rates in the perspective of NP applications. Monoclonal antibodies (mAbs) are the cornerstone of the treatment of several types of tumors, but their use in pregnant women is not clearly defined. Importantly, the usage of such humanized antibody based biopharmaceuticals during pregnancy is a highly questionable approach because of the unknown capability of maternal IgG transport across the human placenta to the unborn (4). The ex vivo placental perfusion setting is a well-established human model to investigate antibody transfer/transport in late pregnancy. Currently, such fully human monoclonal immunoglobulin (IgG) antibodies that bind with high affinity and specificity to early-stage breast cancer receptor positive tumors are investigated by using the placental perfusion system at materno-fetal barrier.
Collaborations within the DP-iDP:
Collaborating research groups where PhD students could perform their research stay abroad:
Industrial partners:Amgen, Pfizer, Roche, TEVA
Know-how and infrastructure of the research group:Christian Wadsack’s laboratory has longstanding expertise in the field of lipids / lipoproteins in pregnancy and their impact on the human placenta in normal and pathophysiological pregnancies. In order to study transport / transfer of lipids across intact placental barrier two ex vivo placental perfusion systems were assembled and experiments are running frequently with different questions in the laboratory. The laboratory uses a wide range of techniques to follow either biologicals or lipids across the human placenta including inflammatory conditions like pre-eclampsia, diabetes or antiphospholipid syndrome.
All required equipment is available at the department, including a team of research nurses which provide the
laboratory with placentas from the delivery room including all subject characteristics and if necessary clinical
data of the women. Mass spectrometry analyses are performed at the Centre for Medical Research and the Institute
of Medical and Chemical Laboratory Diagnostics, both located at the
Scientific concepts and techniques that students will learn in this laboratory:DP-iDP students will be trained in maternal and fetal lipoprotein biochemistry in early and late pregnancy which includes special techniques (ultracentrifugation and FPLC) for the isolation of the distinct HDL sub-fractions. The students will also learn how to isolate and cultivate primary cells of first-trimester and term human placentas (normal and out of placentas from pregnancy diseases),