{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T23:02:09Z","timestamp":1790118129375,"version":"4.0.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Zinc oxide (ZnO)-containing nanomaterials may elicit toxic responses in environmental organisms such as earthworms. In this study, we investigate the time-dependent gene expression and metabolomic response in earthworms exposed to ZnO and Mn-doped ZnO (ZnO:Mn) nanomaterials (both at 850 mg\/kg soil) and MnCl\n                      <jats:sub>2<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Earthworms were exposed to ZnO nanomaterial (850 mg\/kg soil) for 2, 3, 4, or 7 days, to ZnO:Mn nanomaterial (850 mg\/kg soil) for 2, 4, 7, or 14 days, and to MnCl\n                      <jats:sub>2<\/jats:sub>\n                      (45 mg\/kg soil) for 14 days. Time-dependent molecular responses were characterized by transcriptomic and metabolomic analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Discussion<\/jats:title>\n                    <jats:p>\n                      Strong differential gene expression was observed after 4 and 2 days of exposure to ZnO and ZnO:Mn, respectively. Moderate differential gene expression was observed after 14 days of exposure to ZnO:Mn and MnCl\n                      <jats:sub>2<\/jats:sub>\n                      . Gene ontology (GO) enrichment analysis revealed that differentially expressed genes (DEGs) in earthworms exposed to ZnO were commonly associated with muscles and earthworm movements. Genes upregulated after 2 days of exposure to ZnO:Mn were linked to GO terms associated with microtubule-based structures mediating cellular motility. Downregulated genes were enriched to GO terms among which several were related to energy metabolism. For earthworms exposed to ZnO:Mn and MnCl\n                      <jats:sub>2<\/jats:sub>\n                      for 14 days, few DEGs were involved in GO terms related to diverse biological implications. Aligning with the limited number of GO terms observed, metabolomic disruptions only included increased glutamate and a tendency for increased aspartate in response to MnCl\n                      <jats:sub>2<\/jats:sub>\n                      and ZnO:Mn exposure for 14 days, respectively. Other amino acids and the oxidized-to-reduced glutathione ratio, an indicator of oxidative stress, were not affected. In summary, exposing earthworms to ZnO and ZnO:Mn nanomaterials induced a transient response in differential gene expression related to muscle biology, energy metabolism, and translation, which largely disappeared after 14 days. Combined with minimal metabolomic changes, these findings do not point to substantial long-term ecotoxic effects.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/ftox.2026.1927574","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:10:31Z","timestamp":1790115031000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated transcriptomic and metabolomic ecotoxicity assessment of earthworms exposed to ZnO and Mn-doped ZnO nanomaterials"],"prefix":"10.3389","volume":"8","author":[{"given":"Henk J.","family":"van Lingen","sequence":"first","affiliation":[{"name":"Laboratory of Systems & Synthetic Biology, Wageningen University & Research","place":["Wageningen, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paraskevi","family":"Zagana","sequence":"additional","affiliation":[{"name":"Metabolic Engineering and Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH\/ICE-HT)","place":["Patras, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changlin","family":"Ke","sequence":"additional","affiliation":[{"name":"Laboratory of Systems & Synthetic Biology, Wageningen University & Research","place":["Wageningen, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Saccenti","sequence":"additional","affiliation":[{"name":"Laboratory of Systems & Synthetic Biology, Wageningen University & Research","place":["Wageningen, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Baccaro","sequence":"additional","affiliation":[{"name":"Division of Toxicology, Wageningen University & Research","place":["Wageningen, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I.","family":"Klapa","sequence":"additional","affiliation":[{"name":"Metabolic Engineering and Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH\/ICE-HT)","place":["Patras, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoi G.","family":"Lada","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Molecular Spectroscopy, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH\/ICE-HT)","place":["Patras, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico W.","family":"van den Brink","sequence":"additional","affiliation":[{"name":"Division of Toxicology, Wageningen University & Research","place":["Wageningen, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Suarez-Diez","sequence":"additional","affiliation":[{"name":"Laboratory of Systems & Synthetic Biology, Wageningen University & Research","place":["Wageningen, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1007\/s11244-022-01703-5","article-title":"Improved photoresponse of sunlight-driven Mnn+-ZnO (n = 2, 4, 7) nanostructures: a study of oxidative degradation of methylene blue","volume":"65","author":"Aulakh","year":"2022","journal-title":"Top. 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