Understanding the molecular mechanisms underlying uterine spiral artery remodeling, a critical process for pregnancy and fetal well-being: importance of chymases.
Final Report Abstract
The main goal of this project was to understand the mechanisms by which mast cells (MCs) and their mediator, chymase, positively influence the remodeling of spiral arteries (SA) during pregnancy. This process is critical for a healthy pregnancy as it is linked to the adaptation of blood flow and fetal supply. Likewise, this study explored the impact of Bisphenol A (BPA) – an environmental chemical mainly used for the production of plastics and epoxy resins - on the cellular regulation of SA remodeling. Moreover, the role of estrogen receptor α (ERα) signaling in chymase-producing cells (Mcpt5+) during pregnancy was investigated using a mouse model. The project addressed two main questions: • The influence of MCs and chymase on uterine vascular smooth muscle cells (uVSMCs), extracellular matrix (ECM), extravillous trophoblast cells (EVTs), and angiogenesis in the context of SA remodeling in vitro. • The importance of ERα signaling in chymase-producing cells for fetal development and pregnancy outcome. In vitro experiments with murine and human cell lines as well as primary cells showed that MCs and chymase switch the phenotype of uVSMCs from a contractile to a synthetic state. This transition promotes the migration and proliferation of uVSMCs, which is considered an important step in the remodeling of SAs during pregnancy. Additionally, the role of BPA, a widely used environmental chemical with hormone-like properties, was examined. The results demonstrated that BPA significantly disrupted the ability of MCs to support cellular processes essential for a successful SA remodeling, particularly by impairing their promotion of EVTs and uVSMCs migration. In a mouse model, the impact of ERα on the function of chymase-producing cells during pregnancy was analyzed. It was shown that the absence of ERα in Mcpt5+ cells led to impaired SA remodeling and placental insufficiency. This suggests that ERα plays a central role in regulating MCs during pregnancy. In conclusion, this project not only contributes to a better understanding of pregnancy complications but also opens up new perspectives for therapeutic approaches, particularly with regard to hypertensive pregnancy disorders. Moreover, the findings highlight the potential dangers of BPA and emphasize the importance of minimizing exposure to harmful environmental chemicals during pregnancy. These insights have both scientific and societal relevance and could help develop future health prevention strategies and regulatory measures.
Publications
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Poster Presentation „Bisphenol A disturbs the migration of extravillous trophoblast cells in response to mast cells and their mediator chymase in vitro”; HIGRADE conference; Helmholtz Centre for Environmental Research (UFZ); Leipzig, Germany
Ningjuan Zhang
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Insights into Early-Pregnancy Mechanisms: Mast Cells and Chymase CMA1 Shape the Phenotype and Modulate the Functionality of Human Trophoblast Cells, Vascular Smooth-Muscle Cells and Endothelial Cells. Cells, 11(7), 1158.
Zhang, Ningjuan; Schumacher, Anne; Fink, Beate; Bauer, Mario; Zenclussen, Ana Claudia & Meyer, Nicole
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Oral presentation (Invited speaker) „Mast cells”; 64th Congress of the German Society for Gynecology and Obstetrics (DGGG); Munich, Germany;
Nicole Meyer
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Poster Presentation „Bisphenol A disturbs the migration of extravillous trophoblast cells in response to mast cells and their mediator chymase in vitro”; 24th International Federation of Fertility Societies (IFFS); Athen, Greece;
Ningjuan Zhang
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Gefährdung durch Alltagschemikalien. Die Gynäkologie, 56(9), 633-640.
Fischer, Florence; Zenclussen, Ana C. & Meyer, Nicole
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Mastzellen. Reproduktionsimmunologie, 113-128. Springer Berlin Heidelberg.
Meyer, Nicole
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Oral presentation (Invited speaker) „Environment and Human Health“; Collaboration Intensive Programme on Environment, Climate Change and Health by Leipzig University, Charité- Universitätsmedizin Berlin und Chiba University Japan; Leipzig, Germany
Nicole Meyer
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Poster Presentation „Bisphenol A Negatively Impacts Cellular Vascularization Processes Related to Early Pregnancy“; FEBS-IUBMB-ENABLE conference; Köln, Germany;
Federica Romanelli
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Oral and Poster Presentation „Can Bisphenol A exposure threaten life at its very beginning? BPA impact on early pregnancy vascularization processes“; HIGRADE conference; Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany
Federica Romanelli
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Oral presentation (Invited speaker) „Unlocking the Secrets of Early Pregnancy: Environmental Chemicals and Their Role in the Dynamics of Vascular Remodeling and Fetal Development“; 43rd Annual Meeting of the American Society for Reproductive Immunology; Houston, USA
Nicole Meyer
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Oral presentation „Guardians of pregancy: mast cells and the threat of endocrine disruptors to child health“; DZKJ German Center for Child and Adolescent Health Kick-off Retreat; Leipzig, Germany
Nicole Meyer
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Poster Presentation „Bisphenol A Negatively Impacts Cellular Vascularization Processes Related to Early Pregnancy“; IP Day Healthy Planet; Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany;
Federica Romanelli
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Poster Presentation „Exploring the Importance of Estrogen Receptor α in Mast Cells Throughout Pregnancy: Insights from a Mouse Model”; Annual Conference of the International Federation of Placenta Associations (IFPA 2024); Montreal, Canada
Federica Romanelli
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Umweltchemikalien: Verborgene Gefahr für Mutter und Kind?. Hebammen Wissen, 6(2), 30-33.
Meyer, Nicole; Fischer, Florence & Zenclussen, Ana Claudia
