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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\u2010 and pregnancy stage\u2010specific deregulation of placental signaling from a single exposure of human placental explants to physiologically relevant concentrations of engineered (silica (SiO<jats:sub>2<\/jats:sub>) and titanium dioxide (TiO<jats:sub>2<\/jats:sub>) 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)\u2010associated proteins. Moreover, conditioned media (CM) from NP\u2010exposed explants induce pronounced anti\u2010angiogenic and anti\u2010vasculogenic 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\u2010mediated toxicity by holistic secretomics approaches to ensure the development of safe nanotechnologies.<\/jats:p>","DOI":"10.1002\/advs.202401060","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T06:04:32Z","timestamp":1716185072000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Nanoparticles Dysregulate the Human Placental Secretome with Consequences on Angiogenesis and Vascularization"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7598-9357","authenticated-orcid":false,"given":"Battuja","family":"Dugershaw\u2010Kurzer","sequence":"first","affiliation":[{"name":"Laboratory for Particles\u2010Biology Interactions Swiss Federal Laboratories for 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