Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Mihalic, Z.
Neutrophil function in pregnancy
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2024. pp.
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Kargl Julia
- Wadsack Christian
- Altmetrics:
- Abstract:
- Pregnancy represents a unique period during which the mother and fetus must co-exist. In the early stages of placental development, maternal immune cells located at the feto-maternal interface, or decidua basalis (DB), must facilitate the invasion of extravillous trophoblasts (EVTs) to ensure proper placental development. Immune cell function at the DB, particularly natural killer cells (NKs) and macrophages, has been described to have an important role in placental development, with their malfunction linked to the development of pregnancy complications. Additionally, neutrophils have been observed to enter the DB, stimulating regulatory T cells, and their depletion has been associated with abnormal placental development. However, their precise function during pregnancy remains to be thoroughly investigated. Building upon previous research, we hypothesized that neutrophils infiltrate the DB during the early stages of placental development, exhibiting a tissue-specific phenotype and function. Moreover, we aimed to investigate the impact of neutrophil granular protein release on EVTs function. In this thesis, we initially evaluated immune infiltration in the DB compared with the EVT uninvaded part of the tissue, known as decidua parietalis (DP), demonstrating a substantial presence of neutrophils within the DB. Through a comprehensive analysis, we categorized the phenotype of tissue neutrophils and blood neutrophils, revealing that neutrophils alter their marker expression upon migration into the tissue. Furthermore, we identified three distinct subsets of neutrophils within the tissue and observed differential expression of numerous markers among these populations. Upon investigating the effect of neutrophil-derived myeloperoxidase (MPO) on EVTs, we found that MPO internalization promotes JEG-3 cell line migration and invasion, elucidating the crucial role of neutrophils invasion into the DB. Our study provides a comprehensive picture of the immune landscape and specific surface protein expression pattern on neutrophils at the feto-maternal interface. To the best of our knowledge, this is the first study that focuses on the specific subpopulation of neutrophil infiltrating the DB and their derived protein effects on EVTs.