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Forschung Gottfried Schatz Forschungszentrum Forschungszentren und Institute Med Uni Graz

Forschungsteam Gauster

Forschungsschwerpunkt Reproduktion, Schwangerschaft und Regeneration

Teamleiter: Martin Gauster

Fokus: Eine fehlerhafte Entwicklung der Plazenta in der Frühphase der Schwangerschaft wird mit Schwangerschaftspathologien wie etwa Präeklampsie und intrauteriner Wachstumsrestriktion assoziiert, die in weiterer Folge schädliche Einflüsse auf die Mutter und das Kind, sogar noch im späteren Leben, haben könnten. Aus diesem Grund richtet sich der Fokus auf inflammatorische Prozesse in der frühen Plazentaentwicklung und auf Mechanismen, die in Plazenta-assoziierte Schwangerschaftspathologien involviert sind.

Vernetzung: Wir kooperieren u.a. mit Desoye Gernot, Hiden Ursula, Hirschmugl Birgit, Wadsack Christian (Universitätsklinik für Frauenheilkunde und Geburtshilfe), Cvirn Gerhard (Lehrstuhl für Physiologische Chemie), Giovanny Rodriguez Blanco (Klinisches Institut für Medizinische und Chemische Labordiagnostik), Julia Kargl (Lehrstuhl für Pharmakologie), Alexander Deutsch (Klinische Abteilung für Hämatologie).

Projekte

Maternal platelets and extravillous trophoblasts

Recently our published research show that in progressing pregnancy maternal platelets are partially activated at the placental surface during their passage through the placenta, and thereby release their stored platelet factors. The release of these platelet-derived factors seems to have a significant impact on the production of many important pregnancy hormones. Moreover, our new findings reveal that maternal platelets can leave the bloodstream, when entering into the placenta and apparently can leak into intercellular spaces of fetal cells that anchor the placenta to the uterine wall. Subsequent microscopic investigations suggest activation of the maternal platelets in these intercellular spaces. Based on these observations, the influence of platelet activation and the release of platelet-derived factors on fetal placental cells will be investigated in this follow-up project. The effect of the platelet- derived factors on cell differentiation and invasiveness of the placenta cells into the maternal uterine wall will be investigated in detail. These questions have not been investigated before and represent a new scientific concept that opens up novel mechanistic and therapeutic approaches for pregnancy diseases that are associated with increased platelet activation at the placental attachment zone.
Fördergeber: FWF
Laufzeit: 2022 - 2026
PI: Gauster

Placenta-educated maternal platelets (PEPs)

Platelets are small, circulating blood cells, which are built in the bone marrow. Recent biomolecular analyses of platelets suggest aberrant RNA and protein profiles under pathological conditions, including cardiovascular disease, blood cancer and solid tissue tumors. In the case of cancer, platelets have been described to be educated by tumor-released factors. This fascinating concept may be translated to pregnancy, when placenta released factors potentially modify the content and function of maternal platelets. In human pregnancy, maternal platelets show increased activity that is even more increased in the pregnancy disorder preeclampsia. To prove the concept of placenta-educated platelets, this project will study the influence of pregnancy and placenta-related factors on the fromation and content of platelets in different stages of gestation. For this purpose, platelets from healthy pregnant donors, who donated blood in all three trimesters of gestation, and those with preeclampsia, will be subjected to RNA and protein analyses. Moreover, functional assays, such as energy production or formation of aggregates of platelets with other circulating blood cells will be performed. In addition, influence of pregnancy and placenta-related factors on the formation of platelets will be elucidated in a human bone marrow cell line and a rat model. This project is of significance as it could fill a gap in our knowledge on the maternal platelet content and it may contribute to our understanding of pregnancy pathologies related to a prothrombotic state. Identification of different platelet subgroups in pregnancy, with different response to anti-platelet drugs could provide the basis for new therapeutic strategies.
Fördergeber: FWF
Laufzeit: 2025 - 2029
PI: Gauster

LYVE-1 Hofbauer cells in preeclampsia

Preeclampsia is a serious pregnancy complication characterized by the onset or worsening of high blood pressure and increased protein in the urine after the twentieth week of pregnancy. In pregnancies complicated by preeclampsia, the placenta, a vital organ for pregnancy, undergoes significant changes leading to inflammation, vascular problems, and abnormal placental tissue structure. One crucial type of cells found in the placenta, known as Hofbauer cells, are placental macrophages. These cells express a receptor called LYVE-1 and interact with hyaluronan, an important component of the connective tissue. In preeclampsia, Hofbauer cells may not function properly, potentially contributing to placental dysfunction. This joint bilateral research project aims to delve into this phenomenon by examining data from placental tissue samples and investigating how Hofbauer cells interact with other cells in the placenta. For this purpose, we are using computational methods to understand how these cells develop and change during preeclampsia. Additionally, we are conducting experiments to directly assess how Hofbauer cells affect the structure and function of placental blood vessels. This project is significant because it could fill a gap in our understanding of how Hofbauer cells regulate placental tissue structure, especially in the context of preeclampsia. By gaining insights into these processes, we hope to advance our understanding of placental health and potentially identify new therapeutic targets for treating preeclampsia.
Fördergeber: FWF
Laufzeit: 2024 - 2027
PI: Gauster

Trophoblastic anticoagulant proteins at the implantation front

Human placentation depends on sufficient invasion of trophoblasts into the endometrium under local anticoagulant conditions. Invovled anticoagulant factors must be tightly controlled with respect to the time window and location of their expression at the embryo implantation site. However, a detailed characterization of the human trophoblastic anticoagulant machinery during a very early stage of placentation does not yet exist. Hence, this project’s results are expected to give new insight into the spatial-temporal expression pattern of the human trophoblastic anticoagulant machinery at the implantation site, and the trophoblastic anticoagulant machinery in cases of recurrent miscarriage.
Fördergeber: European Commission / HORIZON-MSCA-DN
Laufzeit: 2025 - 2028
PI: Gauster

Invasive properties of trophoblast subtypes during implantation and early placentation

So far, the processes during implantation and early placentation in the human are mostly unclear. Especially, the knowledge on the behavior of the trophectoderm-derived first trophoblast (mononuclear as well as syncytial) is mostly based on animal studies or few images from archival specimens. Hence, this project’s results are expected to give new insight into the mechanisms of blastocyst penetration through the uterine epithelium by using lightsheet microscopy to develop 3D images of the invasion process. Moreover, the necessity to form an early invasive syncytiotrophoblast for human implantation will be challenged by using confocal microscopy and electron microscopy.
Fördergeber: European Commission / HORIZON-MSCA-DN
LAufzeit: 12025 - 2028
PI: Huppertz

LAMB3 – DAG1 axis in endoglandular trophoblast invasion, FWF

Women in Austria currently wish to have at least 2 children on average, but unfortunately many suffer from fertility problems in the first few weeks of pregnancy and even lose their child very early on. Science cannot yet help here, as the basic processes involved in human implantation and placenta development in humans are still largely unknown. During human pregnancy, the fetus is nourished with maternal blood via the placenta. However, this so-called uteroplacental blood flow only starts from the 4th month of pregnancy. Before that, the fetus is nourished by secretions from the glands in the mother`s uterine lining. Only in recent years has it been discovered that during placental development, fetal cells from the placenta invade these uterine glands, thereby connect the glands with the placenta and thus enable the glandular secretions to reach the fetus. It is likely that the role of the uterine glands and their invasion by fetal cells in maintaining a healthy pregnancy has been underestimated. Also, the factors that may dictate this invasion pattern and thus influence reproductive success are still unknown. We want to better understand how these invading fetal cells interact with the maternal uterine glands, potentially contributing to complications in fertility and early pregnancy. However, research into human reproduction poses a particular challenge. Aside from ethical concerns, processes such as implantation and subsequent placentation differ significantly between animals and humans. The applicant has invented novel in vitro model systems for early placenta development. they are used to identify biomarkers, investigate their potential contribution to early placental development, evaluate treatment options and predict response with classical laboratory methods such as histology, molecular biology together with modern bioinformatics. Thereby a potential contribution of these biomarkers to early pregnancy will be investigated. This project offers the opportunity to gain insights into fertility issues and pregnancy-related diseases and thus makes an important contribution to the prevention of diseases that affect women.
Fördergeber: FWF
Laufzeit: 2024 - 2028
PI: Moser

LYMPHO-CHECK: Bioinformatik und Data-Mining in der Lymphomforschung

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoid malignancy in the western world. While immune checkpoint blockade therapy is in clinical practice for a number of cancer types, the response rates for B cell lymphomas remain disappointingly low. Importantly, immune evasive mechanisms are still poorly investigated in B cell lymphomas,which has impeded the progress in developing new therapeutic approaches targeting the lymphoma immune landscape. This bioinformatics project aims to address this gap by investigating the immunomodulatory effects of the NR4A1/p53 axis, two pivotal transcription factors and tumour suppressors.
Fördergeber: FWF
Laufzeit: 2024 - 2029
PI: Feichtinger

Abgeschlossene Projekte

Einfluss adhärenter Blutplättchen auf den Zottentrophoblast

Adhärente mütterliche Blutplättchen stellen eine unterschätzte Quelle für regulierende Faktoren dar, die Trophoblastzellen der Plazenta und deren Interaktion mit zirkulierenden mütterlichen Blutzellen beeinflussen können. In diesem Projekt wird die Hypothese getestet ob Plättchenfaktoren die Zellteilung, Differenzierung und Hormonsekretion von Trophoblasten beeinflussen, und ob mütterliche Immunzellen, die die Plazenta passieren, durch freigesetzte Plättchenfaktoren aktiviert werden.
Laufzeit: 2017-2021
Gefördert durch: FWF

Der Einfluss von Angiotensin II auf das plazentale Fraktalkin

Angiotensin übt seine Wirkung über Angiotensin-Rezeptoren aus, die nebst anderen Organen auch in der Plazenta vorhanden sind. Eine Aktivierung der Angiotensin-Rezeptoren durch Angiotensin II kann unter anderem auch die Ausschüttung einer Reihe entzündungsfördernder Botenstoffe bewirken. Unter diesen entzündungsfördernden Botenstoffen nimmt Fraktalkin eine einzigartige Rolle ein, da es sowohl als gelöster Stoff im Blut transportiert werden kann, als auch an Zellen gebunden vorliegt. In diesem Projekt wird die Hypothese geprüft ob Angiotensin die Synthese und Freisetzung des Fraktalkins in der Plazenta stimuliert und ob dadurch die Bindung und Aktivierung mütterlicher Immunzellen an die Plazenta erhöht wird.
Laufzeit: 2017-2021
Gefördert durch: FWF
Projektpartner: Florian Herse (Charité / MDC Berlin)

Fluss-vermittelte Modulation der villösen Trophoblast Physiologie

In dieser Studie soll der Zusammenhang zwischen der Intensität der Strömungskräfte und der biologischen Reaktion des villösen Trophoblasten untersucht werden. Dabei wird die Hypothese getestet ob unterschiedliche Flussgeschwindigkeiten den zellulären Umsatz, Morphologie, Metablismus, sowie endokrine und inflammatorische Aktivitäten des Trophoblasten beeinflussen. Um diese Zielsetzung zu bearbeiten, wurden drei ineinandergreifende Arbeitspakete definiert, die Experimente mit Trophoblast-Zelllinien, primären Trophoblasten und Explantatkulturen aus Plazentagewebe des ersten Schwangerschaftsdrittels beinhalten.
Laufzeit: 2020-2023
Gefördert durch: OeNB

Plazentales CD39 und CD73 in der humanen Schwangerschaft

Extrazelluläres ATP stellt ein wichtiges Signalmolekül dar, das einige pathologische Effekte im Zuge von Entzündungsvorgängen, Blutplättchenaktivierung und Thrombose moduliert. Extrazelluläres ATP kann durch die zwei Nukleotid-abbauenden Enzyme CD39 und CD73 in AMP und schließlich Adenosin konvertiert, und damit entschärft werden. Dieses Projekt testet die Hypothese ob CD39 und CD73 in der humanen Plazenta bereits ab einer sehr frühen Phase der Schwangerschaft gebildet werden, und ob deren Bildung in Gegenwart von entzündungsfördernden Botenstoffen, verminderter Sauerstoffversorgung oder erhöhter mechanischer Beanspruchung dereguliert sind.
Laufzeit: 2020-2024
Gefördert durch: FWF

Einfluss der Thrombozytenaktivierung auf die endokrine Aktivität der Plazenta

In diesem Projekt wird die Lokalisierung und Aktivierung von mütterlichen Thrombozyten in der humanen Plazenta des ersten Trimenons untersucht. Zudem wird der Einfluss von maternalen Thrombozyten und deren freigesetzte Faktoren auf unterschiedliche Trophoblastsubtypen und deren endokrinen Eigenschaften geklärt. Diese Untersuchungen sollen weitere Einblicke in maternal-fetale Interaktionen bringen und somit den Einfluss überschießender Thrombozytenaktivierung auf potenzielle Schwangerschaftspathologien liefern.
Laufzeit: 2018-2022
Gefördert durch: FWF

Placental explant culture 2.0: Flow culture better mimics the in vivo situation in preeclampsia

Preeclampsia is a pregnancy syndrome with unknown etiology, where placental degeneration may result in the release of pro-inflammatory vesicles into maternal blood. The vesicles affect the maternal vascular system resulting in clinical symptoms of the mother. To elucidate quality and quantity of particles and their effect on the maternal endothelium, we established a novel flow culture system for placental explants simulating various health conditions of pregnancy. This enables the analysis of the effect of released placental particles on maternal endothelial cells under constant fluid flow.
Laufzeit: 2018-2022
Gefördert durch: FWF

Lehrstuhl für Zellbiologie, Histologie und Embryologie

Assoz.-Prof. Priv.-Doz. Mag. Dr.
Martin Gauster

T: +43 316 385 71896

E: martin.gauster(at)medunigraz.at

Forschungsprofil