Healthy Pregnancy

Pregnancy is a time of change. The mothers body undergoes tremendous changes, some visible from the outside, some can be imaged by sonography, other important changes and adaptations go unseen as they happen on cellular and molecular level.

Our goal is to understand those latter changes, many of which are connected to proper placenta development and placenta function, with special focus on situations such as diabetes in pregnancy or pre-eclampsia (PE), in which these adaptations don’t happen as they are supposed to.

Lipids and Lipid Signaling

Christian Wadsack - Teammitglied bei PlancentaLab

Christian Wadsack
PhD, PI

Lipids and fatty acids are key components needed for cellular metabolism and energy storage, to build up cellular membranes, and also as precursors in pathways of hormone synthesis and mediators of inflammation. Thus, lipids and fatty acids are also crucial for placental and fetal development and physiology.

Lipids are broken down by lipases, of which various kinds (so-called families) exist in all biological tissues. Placental dyslipidemia and aberrant activity of lipases as well as altered lipid signaling, and inflammation have been linked to pregnancy complications such as pre-eclampsia and gestational diabetes. Therefore, research on placental lipid metabolism and activity of diverse placental lipases (phospholipase A2 family, DAGL, MGL) was and is a key interest in our lab. We expect that our work in this field will provide novel insights into the functions of these enzymes in health and disease.

Berger N, van der Wel T, Hirschmugl B, Baernthaler T, Gindlhuber J, Fawzy N, Eichmann T, Birner-Gruenberger R, Zimmermann R, van der Stelt M, Wadsack C. Inhibition of diacylglycerol lipase β modulates lipid and endocannabinoid levels in the ex vivo human placenta. Front Endocrinol (Lausanne). 2023 Feb 14;14:1092024. doi: 10.3389/fendo.2023.1092024. PMID: 36864832; PMCID: PMC9971001.

Berger N, Allerkamp H, Wadsack C. Serine Hydrolases in Lipid Homeostasis of the Placenta-Targets for Placental Function? Int J Mol Sci. 2022 Jun 20;23(12):6851. doi: 10.3390/ijms23126851. PMID: 35743292; PMCID: PMC9223866.

Hirschmugl B, Desoye G, Catalano P, Klymiuk I, Scharnagl H, Payr S, Kitzinger E, Schliefsteiner C, Lang U, Wadsack C, Hauguel-de Mouzon S. Maternal obesity modulates intracellular lipid turnover in the human term placenta. Int J Obes (Lond). 2017 Feb;41(2):317-323. doi: 10.1038/ijo.2016.188. Epub 2016 Oct 26. PMID: 27780978; PMCID: PMC5309341.

Schliefsteiner C, Hirschmugl B, Kopp S, Curcic S, Bernhart EM, Marsche G, Lang U, Desoye G, Wadsack C. Maternal Gestational Diabetes Mellitus increases placental and foetal lipoprotein-associated Phospholipase A2 which might exert protective functions against oxidative stress. Sci Rep. 2017 Oct 3;7(1):12628. doi: 10.1038/s41598-017-13051-6. PMID: 28974763; PMCID: PMC5626711.

Diabetes, Obesity, lifestyle choices and interventions

Gernot Desoye - Teammitglied bei PlancentaLab

Gernot Desoye
PhD, PI

The maternal glucose-insulin axis is crucial for metabolic adaptations needed for a healthy pregnancy. Both obesity and diabetes are becoming more and more prevalent in Western societies, making these conditions in pregnancy an interesting target to study. While gestational diabetes develops over the course of the pregnancy, obesity or pre-existing maternal diabetes impact a pregnancy from day one.

Therefore, it is of special interest to investigate the effects of a derailed maternal metabolism in first trimester, which has been the focus of our latest studies.
Furthermore, our research interest includes the impact of lifestyle choices such as smoking and physical activity on pregnancy outcome, as these are factors that mothers can directly influence.

Bandres-Meriz J, Dieberger AM, Hoch D, Pöchlauer C, Bachbauer M, Glasner A, Niedrist T, van Poppel MNM, Desoye G. Maternal Obesity Affects the Glucose-Insulin Axis During the First Trimester of Human Pregnancy. Front Endocrinol (Lausanne). 2020 Oct 9;11:566673. doi: 10.3389/fendo.2020.566673. PMID: 33154737; PMCID: PMC7586307.

Bandres-Meriz J, Kunz C, Havelund JF, Færgeman NJ, Majali-Martinez A, Ensenauer R, Desoye G. Distinct maternal metabolites are associated with obesity and glucose-insulin axis in the first trimester of pregnancy. Int J Obes (Lond). 2023 Apr 7. doi: 10.1038/s41366-023-01295-4. Epub ahead of print. PMID: 37029207.

Majali-Martinez A, Weiss-Fuchs U, Miedl H, Forstner D, Bandres-Meriz J, Hoch D, Djelmis J, Ivanisevic M, Hiden U, Gauster M, Desoye G. Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion. Int J Mol Sci. 2021 Oct 12;22(20):10989. doi: 10.3390/ijms222010989. PMID: 34681648; PMCID: PMC8539403.

Hoch D, Majali-Martinez A, Bankoglu EE, Stopper H, Glasner A, Desoye G, Gauster M, Hiden U. Maternal Smoking in the First Trimester and its Consequence on the Early Placenta. Lab Invest. 2023 Jan 10;103(5):100059. doi: 10.1016/j.labinv.2022.100059. Epub ahead of print. PMID: 36801640.

Placental vascular function

Nilüfer Kamali Simsek - Teammitglied bei PlancentaLab

Nilüfer Kamali Simsek
MSc

Hanna Allerkamp - Teammitglied bei PlancentaLab

Hanna Allerkamp
PhD, PI

As a consequence of its main functions, the placenta is an organ extremely rich in vasculature. Endothelial cells line the entirety of blood vessels and are responsive to changes in their microenvironment. PIEZO1 is a mechano-sensitive, Ca2+-permeable ion channel that mediates several key endothelial functions.

It can be directly activated by shear stress resulting from blood flow, which leads to a calcium influx which in turn has effect on organization and alignment of endothelial cells, on their vascular barrier properties and cell migration. Moreover, it was found that PIEZO1 contributes to endothelial inflammation via integrin activation.
Preeclampsia is associated with impaired placental function and inflammation, but most mechanistic links remain unrevealed. In neurons, transient receptor potential (TRP) channels, activated by pro-inflammatory mediators, are involved in PIEZO1 regulation. Translating to placenta, we aim to understand the interplay of PIEZO1 and TRPV4 in the normal and preeclamptic placental endothelium. Our findings and observations will likely increase our current understanding of pre-eclampsia, how blood pressure derails in this pregnancy conditions, and how it is related to placental inflammation and endothelial dysfunction.

Allerkamp HH, Pole T, Boukham A, James JL, Clark AR. Pregnancy-specific uterine vascular reactivity: a data-driven computational model of shear-dependent, myogenic, and mechanical radial artery features. Am J Physiol Heart Circ Physiol. 2022 Jul 1;323(1):H72-H88. doi: 10.1152/ajpheart.00693.2021. Epub 2022 Apr 22. PMID: 35452318.

Allerkamp HH, Clark AR, Lee TC, Morgan TK, Burton GJ, James JL. Something old, something new: digital quantification of uterine vascular remodelling and trophoblast plugging in historical collections provides new insight into adaptation of the utero-placental circulation. Hum Reprod. 2021 Feb 18;36(3):571-586. doi: 10.1093/humrep/deaa303. PMID: 33600565.