{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:07:00Z","timestamp":1791994020596,"version":"4.4.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23KJ1958"],"award-info":[{"award-number":["JP23KJ1958"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K18345"],"award-info":[{"award-number":["JP23K18345"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-23372-6","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T18:27:06Z","timestamp":1762885626000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Role of ferroptosis-related GPX4 signaling in the fusion of human trophoblast cells"],"prefix":"10.1038","volume":"15","author":[{"given":"Kanoko","family":"Yoshida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Kusama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiho","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Horiuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikihiro","family":"Yoshie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Tamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"23372_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.biocel.2004.05.014","volume":"37","author":"P Bischof","year":"2005","unstructured":"Bischof, P. & Irminger-Finger, I. The human cytotrophoblastic cell, a mononuclear chameleon. Int J Biochem Cell Biol 37, 1\u201316. https:\/\/doi.org\/10.1016\/j.biocel.2004.05.014 (2005).","journal-title":"Int J Biochem Cell Biol"},{"key":"23372_CR2","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1038\/nri1897","volume":"6","author":"A Moffett","year":"2006","unstructured":"Moffett, A. & Loke, C. Immunology of placentation in eutherian mammals. Nat Rev Immunol 6, 584\u2013594. https:\/\/doi.org\/10.1038\/nri1897 (2006).","journal-title":"Nat Rev Immunol"},{"issue":"Suppl","key":"23372_CR3","doi-asserted-by":"publisher","first-page":"S87","DOI":"10.1016\/j.placenta.2011.11.003","volume":"33","author":"MS Weedon-Fekj\u00e6r","year":"2012","unstructured":"Weedon-Fekj\u00e6r, M. S. & Task\u00e9n, K. Review: Spatiotemporal dynamics of hCG\/cAMP signaling and regulation of placental function. Placenta 33(Suppl), S87-91. https:\/\/doi.org\/10.1016\/j.placenta.2011.11.003 (2012).","journal-title":"Placenta"},{"issue":"Suppl A","key":"23372_CR4","doi-asserted-by":"publisher","first-page":"S49","DOI":"10.1016\/j.placenta.2008.10.011","volume":"30","author":"M Gauster","year":"2009","unstructured":"Gauster, M., Moser, G., Orendi, K. & Huppertz, B. Factors involved in regulating trophoblast fusion: Potential role in the development of preeclampsia. Placenta 30(Suppl A), S49-54. https:\/\/doi.org\/10.1016\/j.placenta.2008.10.011 (2009).","journal-title":"Placenta"},{"key":"23372_CR5","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","volume":"171","author":"BR Stockwell","year":"2017","unstructured":"Stockwell, B. R. et al. Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171, 273\u2013285. https:\/\/doi.org\/10.1016\/j.cell.2017.09.021 (2017).","journal-title":"Cell"},{"key":"23372_CR6","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.1080\/15548627.2020.1810918","volume":"17","author":"X Chen","year":"2021","unstructured":"Chen, X., Li, J., Kang, R., Klionsky, D. J. & Tang, D. Ferroptosis: Machinery and regulation. Autophagy 17, 2054\u20132081. https:\/\/doi.org\/10.1080\/15548627.2020.1810918 (2021).","journal-title":"Autophagy"},{"key":"23372_CR7","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201800311","volume":"19","author":"GC Forcina","year":"2019","unstructured":"Forcina, G. C. & Dixon, S. J. GPX4 at the crossroads of lipid homeostasis and ferroptosis. Proteomics 19, e1800311. https:\/\/doi.org\/10.1002\/pmic.201800311 (2019).","journal-title":"Proteomics"},{"key":"23372_CR8","doi-asserted-by":"publisher","first-page":"7038","DOI":"10.1111\/febs.16059","volume":"289","author":"J Liu","year":"2022","unstructured":"Liu, J., Kang, R. & Tang, D. Signaling pathways and defense mechanisms of ferroptosis. Febs j 289, 7038\u20137050. https:\/\/doi.org\/10.1111\/febs.16059 (2022).","journal-title":"Febs j"},{"key":"23372_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101107","volume":"23","author":"M Dodson","year":"2019","unstructured":"Dodson, M., Castro-Portuguez, R. & Zhang, D. D. NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis. Redox Biol 23, 101107. https:\/\/doi.org\/10.1016\/j.redox.2019.101107 (2019).","journal-title":"Redox Biol"},{"key":"23372_CR10","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.00099-20","author":"L Baird","year":"2020","unstructured":"Baird, L. & Yamamoto, M. The molecular mechanisms regulating the KEAP1-NRF2 pathway. Mol Cell Biol https:\/\/doi.org\/10.1128\/mcb.00099-20 (2020).","journal-title":"Mol Cell Biol"},{"key":"23372_CR11","doi-asserted-by":"publisher","first-page":"39387","DOI":"10.1074\/jbc.M111.279893","volume":"286","author":"S Bindu","year":"2011","unstructured":"Bindu, S. et al. Translocation of heme oxygenase-1 to mitochondria is a novel cytoprotective mechanism against non-steroidal anti-inflammatory drug-induced mitochondrial oxidative stress, apoptosis, and gastric mucosal injury. J Biol Chem 286, 39387\u201339402. https:\/\/doi.org\/10.1074\/jbc.M111.279893 (2011).","journal-title":"J Biol Chem"},{"key":"23372_CR12","doi-asserted-by":"publisher","first-page":"3846217","DOI":"10.1155\/2022\/3846217","volume":"2022","author":"S Han","year":"2022","unstructured":"Han, S. et al. HO-1 contributes to luteolin-triggered ferroptosis in clear cell renal cell carcinoma via increasing the labile iron pool and promoting lipid peroxidation. Oxid Med Cell Longev 2022, 3846217. https:\/\/doi.org\/10.1155\/2022\/3846217 (2022).","journal-title":"Oxid Med Cell Longev"},{"key":"23372_CR13","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1146\/annurev-pathol-012513-104649","volume":"10","author":"SA Oakes","year":"2015","unstructured":"Oakes, S. A. & Papa, F. R. The role of endoplasmic reticulum stress in human pathology. Annu Rev Pathol 10, 173\u2013194. https:\/\/doi.org\/10.1146\/annurev-pathol-012513-104649 (2015).","journal-title":"Annu Rev Pathol"},{"key":"23372_CR14","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1002\/hep.32562","volume":"77","author":"A Ajoolabady","year":"2023","unstructured":"Ajoolabady, A. et al. Endoplasmic reticulum stress in liver diseases. Hepatology 77, 619\u2013639. https:\/\/doi.org\/10.1002\/hep.32562 (2023).","journal-title":"Hepatology"},{"key":"23372_CR15","doi-asserted-by":"publisher","first-page":"15186","DOI":"10.3390\/ijms232315186","volume":"23","author":"A Merighi","year":"2022","unstructured":"Merighi, A. & Lossi, L. Endoplasmic reticulum stress signaling and neuronal cell death. Int J Mol Sci 23, 15186. https:\/\/doi.org\/10.3390\/ijms232315186 (2022).","journal-title":"Int J Mol Sci"},{"key":"23372_CR16","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1089\/dna.2019.5097","volume":"39","author":"W Li","year":"2020","unstructured":"Li, W., Li, W., Leng, Y., Xiong, Y. & Xia, Z. Ferroptosis is involved in diabetes myocardial ischemia\/reperfusion injury through endoplasmic reticulum stress. DNA Cell Biol 39, 210\u2013225. https:\/\/doi.org\/10.1089\/dna.2019.5097 (2020).","journal-title":"DNA Cell Biol"},{"key":"23372_CR17","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/s41419-020-2299-1","volume":"11","author":"M Xu","year":"2020","unstructured":"Xu, M. et al. Ferroptosis involves in intestinal epithelial cell death in ulcerative colitis. Cell Death Dis 11, 86. https:\/\/doi.org\/10.1038\/s41419-020-2299-1 (2020).","journal-title":"Cell Death Dis"},{"key":"23372_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109608","volume":"114","author":"T Zeng","year":"2023","unstructured":"Zeng, T. et al. rmMANF prevents sepsis-associated lung injury via inhibiting endoplasmic reticulum stress-induced ferroptosis in mice. Int Immunopharmacol 114, 109608. https:\/\/doi.org\/10.1016\/j.intimp.2022.109608 (2023).","journal-title":"Int Immunopharmacol"},{"key":"23372_CR19","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.1007\/s43032-023-01193-0","volume":"30","author":"X Shen","year":"2023","unstructured":"Shen, X., Obore, N., Wang, Y., Yu, T. & Yu, H. The role of ferroptosis in placental-related diseases. Reprod Sci 30, 2079\u20132086. https:\/\/doi.org\/10.1007\/s43032-023-01193-0 (2023).","journal-title":"Reprod Sci"},{"key":"23372_CR20","doi-asserted-by":"publisher","first-page":"9395","DOI":"10.3390\/ijms23169395","volume":"23","author":"Y Zhang","year":"2022","unstructured":"Zhang, Y., Lu, Y. & Jin, L. Iron metabolism and ferroptosis in physiological and pathological pregnancy. Int J Mol Sci 23, 9395. https:\/\/doi.org\/10.3390\/ijms23169395 (2022).","journal-title":"Int J Mol Sci"},{"key":"23372_CR21","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1002\/ajh.26680","volume":"97","author":"V Sangkhae","year":"2022","unstructured":"Sangkhae, V. et al. Erythroferrone contributes to iron mobilization for embryo erythropoiesis in iron-deficient mouse pregnancies. Am J Hematol 97, 1348\u20131358. https:\/\/doi.org\/10.1002\/ajh.26680 (2022).","journal-title":"Am J Hematol"},{"key":"23372_CR22","first-page":"785","volume":"85","author":"M Awai","year":"1975","unstructured":"Awai, M., Chipman, B. & Brown, E. B. In vivo evidence for the functional heterogeneity of transferrin-bound iron. II. Studies in pregnant rats. J Lab Clin Med 85, 785\u2013796 (1975).","journal-title":"J Lab Clin Med"},{"key":"23372_CR23","doi-asserted-by":"publisher","first-page":"2229","DOI":"10.1093\/humrep\/deq190","volume":"25","author":"M Yoshie","year":"2010","unstructured":"Yoshie, M. et al. Possible role of the exchange protein directly activated by cyclic AMP (Epac) in the cyclic AMP-dependent functional differentiation and syncytialization of human placental BeWo cells. Hum Reprod 25, 2229\u20132238. https:\/\/doi.org\/10.1093\/humrep\/deq190 (2010).","journal-title":"Hum Reprod"},{"key":"23372_CR24","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1016\/s0002-9440(10)64648-2","volume":"157","author":"O Genbacev","year":"2000","unstructured":"Genbacev, O., McMaster, M. T. & Fisher, S. J. A repertoire of cell cycle regulators whose expression is coordinated with human cytotrophoblast differentiation. Am J Pathol 157, 1337\u20131351. https:\/\/doi.org\/10.1016\/s0002-9440(10)64648-2 (2000).","journal-title":"Am J Pathol"},{"key":"23372_CR25","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1038\/s41419-019-1905-6","volume":"10","author":"D Bastida-Ruiz","year":"2019","unstructured":"Bastida-Ruiz, D. et al. The fine-tuning of endoplasmic reticulum stress response and autophagy activation during trophoblast syncytialization. Cell Death Dis 10, 651. https:\/\/doi.org\/10.1038\/s41419-019-1905-6 (2019).","journal-title":"Cell Death Dis"},{"key":"23372_CR26","doi-asserted-by":"publisher","first-page":"801","DOI":"10.3892\/or.2021.7933","volume":"45","author":"X Fu","year":"2021","unstructured":"Fu, X. et al. Endoplasmic reticulum stress, cell death and tumor: Association between endoplasmic reticulum stress and the apoptosis pathway in tumors (Review). Oncol Rep 45, 801\u2013808. https:\/\/doi.org\/10.3892\/or.2021.7933 (2021).","journal-title":"Oncol Rep"},{"key":"23372_CR27","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.jphs.2022.10.003","volume":"150","author":"K Yoshida","year":"2022","unstructured":"Yoshida, K. et al. Endoplasmic reticulum stress-regulated high temperature requirement A1 (HTRA1) modulates invasion and angiogenesis-related genes in human trophoblasts. J Pharmacol Sci 150, 267\u2013274. https:\/\/doi.org\/10.1016\/j.jphs.2022.10.003 (2022).","journal-title":"J Pharmacol Sci"},{"key":"23372_CR28","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/s41598-023-50712-1","volume":"14","author":"K Yoshida","year":"2024","unstructured":"Yoshida, K. et al. Quercetin stimulates trophoblast fusion via the mitochondrial function. Sci Rep 14, 287. https:\/\/doi.org\/10.1038\/s41598-023-50712-1 (2024).","journal-title":"Sci Rep"},{"key":"23372_CR29","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1016\/j.placenta.2015.07.001","volume":"36","author":"SS Teoh","year":"2015","unstructured":"Teoh, S. S., Zhao, M., Wang, Y., Chen, Q. & Nie, G. Serum HtrA1 is differentially regulated between early-onset and late-onset preeclampsia. Placenta 36, 990\u2013995. https:\/\/doi.org\/10.1016\/j.placenta.2015.07.001 (2015).","journal-title":"Placenta"},{"key":"23372_CR30","doi-asserted-by":"publisher","first-page":"4918","DOI":"10.1002\/jcb.26721","volume":"119","author":"K Kusama","year":"2018","unstructured":"Kusama, K., Bai, R. & Imakawa, K. Regulation of human trophoblast cell syncytialization by transcription factors STAT5B and NR4A3. J Cell Biochem 119, 4918\u20134927. https:\/\/doi.org\/10.1002\/jcb.26721 (2018).","journal-title":"J Cell Biochem"},{"key":"23372_CR31","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.3390\/ijms23041955","volume":"23","author":"K Yoshida","year":"2022","unstructured":"Yoshida, K., Yano, A., Kusama, K., Ishikawa, G. & Tamura, K. Alpha 1 antitrypsin regulates trophoblast syncytialization and inflammatory factor expression. Int J Mol Sci 23, 1955. https:\/\/doi.org\/10.3390\/ijms23041955 (2022).","journal-title":"Int J Mol Sci"},{"key":"23372_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.176544","volume":"971","author":"M Azumi","year":"2024","unstructured":"Azumi, M. et al. Involvement of ferroptosis in eribulin-induced cytotoxicity in ovarian clear cell carcinoma. Eur J Pharmacol 971, 176544. https:\/\/doi.org\/10.1016\/j.ejphar.2024.176544 (2024).","journal-title":"Eur J Pharmacol"},{"key":"23372_CR33","doi-asserted-by":"publisher","first-page":"50","DOI":"10.3390\/nu13010050","volume":"13","author":"K Kusama","year":"2020","unstructured":"Kusama, K. et al. Cordyceps militaris fruit body extract decreases testosterone catabolism and testosterone-stimulated prostate hypertrophy. Nutrients 13, 50. https:\/\/doi.org\/10.3390\/nu13010050 (2020).","journal-title":"Nutrients"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-23372-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-23372-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-23372-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T18:27:06Z","timestamp":1762885626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-23372-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,11]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["23372"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-23372-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,11]]},"assertion":[{"value":"30 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"39515"}}