The members of the perinatal research laboratory are trying to understand how pregnancy conditions associated with maternal and foetal overnutrition and low grade inflammation, such as diabetes mellitus and obesity, affect placental function, and which consequences this may entail for the growing foetus.

In order to investigate these interactions of maternal and foetal factors with the placental interface in vitro, we have established methods to isolate and culture different placental primary cells. We are studying the first trimester of pregnancy as well as the term placenta, and focus on human pregnancies. In addition, we have established an ex vivo placenta perfusion model to study maternal to fetal placental transfer.

Maternal and placental determinants of foetal body composition. Offspring of obese and diabetic mothers are at increased risk of being born with excess adiposity as a consequence of their intrauterine environment. Excessive fetal fat accretion reflects additional placental nutrient transfer, suggesting an effect of the maternal environment on placental function. We are using a holistic and multidisciplinary approach integrating maternal (patho)physiology with placental function and foetal development (Gernot Desoye). This implies understanding interactions between maternal exposures with the placenta and its surface facing the maternal circulation, ie the syncytiotrophoblast. Moreover, the placenta also responds to foetal signals through the foeto-placental endothelium thereby adapting to foetal changes associated with maternal diabetes mellitus and obesity. The function of these placental cell types is coordinated to some extent by tissue-resident macrophages (Hofbauer cells).

Effects of maternal and fetal insulin. Maternal insulin concentrations are physiologically elevated during pregnancy, and in particular so, in gestational diabetes mellitus and obesity due to insulin resistance and beta-cell compensation. In Type-I diabetes, pregnant women are treated with exogenous insulin. However, the effects of elevated maternal insulin on placental function are not fully understood. Insulin receptors in the syncytiotrophoblast are mainly expressed in the first trimester, rendering this phase of gestation most critical to regulation by maternal insulin. We therefore investigate the effects of maternal insulin on first trimester trophoblasts. Another hallmark of diabetes and maternal obesity is foetal hyperinsulinemia. Elevated foetal insulin leads to excessive foetal fat accretion, but might also directly have an impact on placental function. Insulin receptors are present on the foeto-placental endothelium. Thus, insulin is one of the foetal signals regulating placental functions such as angiogenesis (Ursula Hiden). 

Lipid metabolism in pregnancy. Another area of interest in the overall context of maternal diabetes and obesity is the role of maternal-to-fetal transfer of lipid and lipoproteins. Importantly, the transport of cholesterol from mother to fetus across the placental barrier has long been neglected. We are investigating by ex vivo placenta perfusion experiments and in vitro cell culture assays if and how cholesterol and other lipids(proteins) cross the different biological barriers of the placenta. Beyond their role for fat deposition, lipids, in particular high-density lipoproteins, may also contribute to pro- and anti-inflammatory conditions in the placenta and the foetal circulation. We are focusing on the composition and functionality of neonatal HDL in order to understand its role on the feto-placental endothelium. The laboratory is also investigating the mechanisms how nanoparticles (NP) interact with the placental barrier. The 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. (Christian Wadsack)

Impact of fetal sex. There is accumulating evidence that gestational diabetes mellitus, placental function and pregnancy outcome depend on foetal sex. It appears that female foetuses and their placentas have a better plasticity to adapt to maternal exposures. We are trying to understand the molecular and cellular differences between placentas of male and female foetuses and their functional consequences (Silvija Tokic).

Human milk oligosaccharides in pregnancy. Most recently we have become interested in Human Milk Oligosaccharides (HMO) as pregnancy specific factors and potential new biomarkers for pregnancy outcomes (Evelyn Jantscher-Krenn). HMO are biologically highly active glycans in breast milk that are already detectable in pregnant women as early as the first trimester. Whereas the effects of HMO in the breast-fed newborn have been increasingly appreciated, the biological role of prenatal HMO is completely unknown. It is also not known whether maternal HMO can pass the placental barrier and enter foetal circulation. We are currently investigating both, maternal HMO during gestation (in serum, urine) and foetal HMO (cord blood), and their respective roles on placental function. The overall goal is to find potential maternal determinants eg. maternal life-style factors such as physical activity and nutrition, for maternal and potentially fetal HMO, which in turn might be correlated with pregnancy outcomes.

Matrix-proteases in trophoblast invasion. In the first trimester of pregnancy the placenta and its main structures and functions have to develop. Thus, this is a critical period in pregnancy, which can be sensitive to changes in the maternal environment. Indeed, pregnancy complications such as preeclampsia and IUGR are thought to originate already in the first trimester of pregnancy due to impairment in trophoblast invasion. We are interested in the role of some matrix-metalloproteinases (MMP2, MMP14, MMP15) during trophoblast invasion and how these are altered by maternal endothelin-1 and pro-inflammatory conditions (Martina Dieber-Rotheneder).

Letzte Aktualisierung: 14.02.2019