麻豆频道

DE
| EN
|
A A+
Suche
Forschung Gottfried Schatz Forschungszentrum
ForschungGottfried Schatz ForschungszentrumForschungszentren und InstituteMed Uni Graz

Forschungsteam Gauster

Forschungsschwerpunkt Reproduktion, Schwangerschaft und Regeneration

Teamleiter: Martin Gauster

Fokus: Eine fehlerhafte Entwicklung der Plazenta in der Frhphase der Schwangerschaft wird mit Schwangerschaftspathologien wie etwa Preklampsie und intrauteriner Wachstumsrestriktion assoziiert, die in weiterer Folge schdliche Einflsse auf die Mutter und das Kind, sogar noch im spteren Leben, haben k枚nnten. Aus diesem Grund richtet sich der Fokus auf inflammatorische Prozesse in der frhen 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 (Universittsklinik fr Frauenheilkunde und Geburtshilfe), Cvirn Gerhard (Lehrstuhl fr 麻豆频道 Chemie), Giovanny Rodriguez Blanco (Klinisches Institut fr 麻豆频道 und Chemische Labordiagnostik), Julia Kargl (Lehrstuhl fr Pharmakologie), Alexander Deutsch (Klinische Abteilung fr Hmatologie).

    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.
    • F枚rdergeber: 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.
    • F枚rdergeber: 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.
    • F枚rdergeber: 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鈥檚 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.
    • F枚rdergeber: 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鈥檚 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.
    • F枚rdergeber: European Commission / HORIZON-MSCA-DN
    • LAufzeit: 12025 - 2028
    • PI: Huppertz

    LAMB3 鈥� 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.
    • F枚rdergeber: 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.
    • F枚rdergeber: FWF
    • Laufzeit: 2024 - 2029
    • PI: Feichtinger

    Abgeschlossene Projekte

    Einfluss adhrenter Blutplttchen auf den Zottentrophoblast

    • Adhrente mtterliche Blutplttchen stellen eine unterschtzte Quelle fr regulierende Faktoren dar, die Trophoblastzellen der Plazenta und deren Interaktion mit zirkulierenden mtterlichen Blutzellen beeinflussen k枚nnen. In diesem Projekt wird die Hypothese getestet ob Plttchenfaktoren die Zellteilung, Differenzierung und Hormonsekretion von Trophoblasten beeinflussen, und ob mtterliche Immunzellen, die die Plazenta passieren, durch freigesetzte Plttchenfaktoren aktiviert werden.
    • Laufzeit: 2017-2021
    • Gef枚rdert durch: FWF

    Der Einfluss von Angiotensin II auf das plazentale Fraktalkin

    • Angiotensin bt seine Wirkung ber 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 Ausschttung einer Reihe entzndungsf枚rdernder Botenstoffe bewirken. Unter diesen entzndungsf枚rdernden Botenstoffen nimmt Fraktalkin eine einzigartige Rolle ein, da es sowohl als gel枚ster Stoff im Blut transportiert werden kann, als auch an Zellen gebunden vorliegt. In diesem Projekt wird die Hypothese geprft ob Angiotensin die Synthese und Freisetzung des Fraktalkins in der Plazenta stimuliert und ob dadurch die Bindung und Aktivierung mtterlicher Immunzellen an die Plazenta erh枚ht wird.
    • Laufzeit: 2017-2021
    • Gef枚rdert durch: FWF
    • Projektpartner: Florian Herse (Charit茅 / MDC Berlin)

    Fluss-vermittelte Modulation der vill枚sen Trophoblast Physiologie

    • In dieser Studie soll der Zusammenhang zwischen der Intensitt der Str枚mungskrfte und der biologischen Reaktion des vill枚sen Trophoblasten untersucht werden. Dabei wird die Hypothese getestet ob unterschiedliche Flussgeschwindigkeiten den zellulren Umsatz, Morphologie, Metablismus, sowie endokrine und inflammatorische Aktivitten des Trophoblasten beeinflussen. Um diese Zielsetzung zu bearbeiten, wurden drei ineinandergreifende Arbeitspakete definiert, die Experimente mit Trophoblast-Zelllinien, primren Trophoblasten und Explantatkulturen aus Plazentagewebe des ersten Schwangerschaftsdrittels beinhalten.
    • Laufzeit: 2020-2023
    • Gef枚rdert durch: OeNB

    Plazentales CD39 und CD73 in der humanen Schwangerschaft

    • Extrazellulres ATP stellt ein wichtiges Signalmolekl dar, das einige pathologische Effekte im Zuge von Entzndungsvorgngen, Blutplttchenaktivierung und Thrombose moduliert. Extrazellulres ATP kann durch die zwei Nukleotid-abbauenden Enzyme CD39 und CD73 in AMP und schlie脽lich Adenosin konvertiert, und damit entschrft werden. Dieses Projekt testet die Hypothese ob CD39 und CD73 in der humanen Plazenta bereits ab einer sehr frhen Phase der Schwangerschaft gebildet werden, und ob deren Bildung in Gegenwart von entzndungsf枚rdernden Botenstoffen, verminderter Sauerstoffversorgung oder erh枚hter mechanischer Beanspruchung dereguliert sind.
    • Laufzeit: 2020-2024
    • Gef枚rdert durch: FWF

    Einfluss der Thrombozytenaktivierung auf die endokrine Aktivitt der Plazenta

    • In diesem Projekt wird die Lokalisierung und Aktivierung von mtterlichen 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 geklrt. Diese Untersuchungen sollen weitere Einblicke in maternal-fetale Interaktionen bringen und somit den Einfluss berschie脽ender Thrombozytenaktivierung auf potenzielle Schwangerschaftspathologien liefern.
    • Laufzeit: 2018-2022
    • Gef枚rdert 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
    • Gef枚rdert durch: FWF

    Lehrstuhl fr Zellbiologie, Histologie und Embryologie

    Assoz.-Prof. Priv.-Doz. Mag. Dr.
    Martin Gauster  
    T: +43 316 385 71896
    E: martin.gauster(at)medunigraz.at
    Martin Gauster

    Team

    Mitarbeiter*innen