Battuja Dugershaw-Kurzer


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Dugershaw-Kurzer

First Name

Battuja

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0000-0002-7598-9357

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2019 - 201912020 - 20243
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Publications 1 - 4 of 4
  • Nanoparticles Dysregulate the Human Placental Secretome with Consequences on Angiogenesis and Vascularization
    Item type: Journal Article
    Dugershaw-Kurzer, Battuja; Bossart, Jonas; Buljan, Marija; et al. (2024)
    Advanced Science
    Exposure to nanoparticles (NPs) in pregnancy is increasingly linked to adverse effects on embryo-fetal development and health later in life. However, the developmental toxicity mechanisms of NPs are largely unknown, in particular potential effects on the placental secretome, which orchestrates many developmental processes pivotal for pregnancy success. This study demonstrates extensive material- and pregnancy stage-specific deregulation of placental signaling from a single exposure of human placental explants to physiologically relevant concentrations of engineered (silica (SiO2) and titanium dioxide (TiO2) NPs) and environmental NPs (diesel exhaust particles, DEPs). This includes a multitude of secreted inflammatory, vascular, and endocrine placental factors as well as extracellular vesicle (EV)-associated proteins. Moreover, conditioned media (CM) from NP-exposed explants induce pronounced anti-angiogenic and anti-vasculogenic effects, while early neurodevelopmental processes are only marginally affected. These findings underscore the potential of metal oxide NPs and DEPs for widespread interference with the placental secretome and identify vascular morphogenesis as a sensitive outcome for the indirect developmental toxicity of different NPs. Overall, this work has profound implications for the future safety assessment of NPs for industrial, commercial, or medical applications in pregnancy, which should consider placenta-mediated toxicity by holistic secretomics approaches to ensure the development of safe nanotechnologies.
  • Investigating the accumulation and translocation of titanium dioxide nanoparticles with different surface modifications in static and dynamic human placental transfer models
    Item type: Journal Article
    Aengenheister, Leonie; Dugershaw-Kurzer, Battuja; Manser, Pius; et al. (2019)
    European Journal of Pharmaceutics and Biopharmaceutics
  • Environmentally relevant UV-light weathering of polystyrene micro- and nanoplastics promotes hepatotoxicity in a human cell line
    Item type: Journal Article
    Englert, Felix H.; Mueller, Fabrice A.; Dugershaw-Kurzer, Battuja; et al. (2023)
    Environmental Science: Nano
    Background: micro- and nanoplastics (MPs/NPs) are global pollutants of concern to human health due to their increasing environmental accumulation and biopersistence. They can reach systemic circulation and distribute to organs, with the liver being a potential target due to its propensity to accumulate particles. However, knowledge of MP and NP hepatotoxicity is scarce and mostly focused on primary particles, which lack environmental relevance. Therefore, the aim of this study was to characterize how UV-weathering influences hepatic cell responses to polystyrene (PS) MPs and NPs. Results: we characterized the effects of primary PS MPs (3 mu m) and NPs (25 and 100 nm) on a human liver cell line (HepaRG) by using high content imaging to profile alterations in pathologically relevant key cellular events, including oxidative stress, lipid accumulation, and nuclear morphology, as well as evaluating differential expression of genes relevant to lipid metabolism, inflammation, and carcinogenesis. We observed no changes in cell viability even at high concentrations (100 mu g ml(-1)) or after prolonged exposure (10 days). However, after UV-induced weathering, PS particles induced cytotoxicity after 24 h at a concentration of 0.1 mu g ml(-1), which is <7% of PS particle concentrations detected in human blood. Other cellular stress responses were observed only upon exposure concentrations of UV-weathered particles more than four times the maximum concentration (12 mu g ml(-1)) detected in human blood. Finally, genes involved in lipid metabolism, inflammation, and carcinogenesis were upregulated upon exposure to most of the tested MPs and NPs. Conclusions: UV-weathering of pristine PS MPs and NPs increases their hepatotoxicity. Cytotoxicity was more pronounced for micro-sized PS particles, but PS NPs induced the expression of genes relevant to the development or progression of fatty liver disease. The data demonstrate the relevance of accounting for effects of weathering on the properties and biological impacts of MPs and NPs and emphasize the need for further studies of chronic MP and NP exposure on tissue function and disease risk.
  • Indirect embryo-fetal risks of nanomaterials
    Item type: Doctoral Thesis
    Dugershaw-Kurzer, Battuja (2022)
    Exposure to engineered and environmental nanomaterials (NMs) is firmly increasing since engineered nanomaterials (ENMs) are being integrated in daily life products, and environmental NMs are being released into the atmosphere due to combustion processes. This is especially of great concern for vulnerable populations, including pregnant women and their unborn children, because prenatal particle exposure has been associated with pregnancy complications, adverse effects in the developing fetus, and diseases later in life. Recent epidemiological and animal studies have confirmed that micro- and nanosized particles can reach the human and rodent placenta (e.g., ambient pollution particles or microplastics and engineered nanoparticles (NPs)). However, the underlying mechanisms of NM-induced fetotoxicity remain largely unknown. In ongoing projects of the group, we found that NMs (titanium dioxide (TiO2), diesel exhaust particles (DEPs), polystyrene (PS) NPs) accumulated in placental tissue without considerable fetal transfer (Chapter 3; Aengenheister, Eur J PharmBiopharm, 2019; Bongaerts, Advanced Biol, 2021, Boos, J of Nanobiotechnol, 2021), which further emphasized the need to study potential indirect fetotoxicity of NMs at the human placenta. We aim to unravel novel indirect fetotoxicity pathways elicited from NM interference with placental tissue viability and signaling pathways. We performed a comprehensive evaluation of the available literature and summarized relevant findings in a review to identify candidate pathways of indirect fetotoxicity and (Chapter 2, Dugershaw, Particle and Fiber Toxicol, 2019), which were incorporated in the study in addition to an unbiased and holistic placental secretomics profiling study to identify further toxicity mechanisms (Chapter 4). We chose nanosized silica dioxide (SiO2), TiO2 (both large-scale produced NMs), and DEPs, based on findings in animal and human studies and due to their societal relevance. With the placenta being the most species-specific organ among mammals, we used advanced human placental explant models. The primary objective is to understand indirect fetotoxic effects of ENMs at the human placental barrier using physiologically relevant human placental models. First objective of this PhD project was to characterize the direct impact of ENMs on placental tissue obtained from early and late pregnancy stages in terms of viability and function. Second objective was to characterize ENM-induced alterations in the release of placental factors and define how these in turn have an impact on angiogenesis (spheroid consisting of primary HUVECs and CAM model). The aim, motivation and hypothesis of the thesis is further explained in Chapter 1. In summary, we could confirm our hypothesis that NMs can extensively interfere with the release of placental mediators in a highly material- and time-dependent manner (Chapter 4). Importantly, these alterations in secretomics profiles affected downstream processes relevant to successful pregnancy and fetal development such as angiogenesis (Chapter 5). This highlights thenurgent need to further intensify research into indirect fetotoxicity mechanisms of NMs and indirect developmental toxicity studies as an integral part of future safety assessment of NM-enabled products and nanomedical drugs (as communicated in our recent reviews from Aengenheister, Placenta, 2021 and Mathiesen, Placenta, 2021) to allow the safe and sustainable use of NMs in pregnancy.
Publications 1 - 4 of 4