{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:40:31Z","timestamp":1790365231004,"version":"4.1.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,14]],"date-time":"2017-08-14T00:00:00Z","timestamp":1502668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,14]],"date-time":"2017-08-14T00:00:00Z","timestamp":1502668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Low oxygen is a typical extrinsic factor for the regulation of trophoblast biological function, including cell migration, invasion and proliferation. Ten-eleven translocation methylcytosine dioxygenase 1 (TET1), an enzyme converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), is transcriptionally activated by hypoxia in cancer cells. Therefore, we focus on the role of TET1 on trophoblast function in a physiologically hypoxic environment (3% oxygen), which is related to early placentation. Here, we found that TET1 was highly expressed in first trimester villi compared with normal term placentas. <jats:italic>In vitro<\/jats:italic>, both TET1 mRNA and protein expression levels in JEG3 cells were increased following exposure to 3% oxygen, and the migration and invasion capacities of JEG3 cells were up-regulated. Furthermore, TET1 knockdown decreased the migration, invasion and proliferation of JEG3 cells exposed to 3% oxygen, and the expression of HIF1\u03b1 and its downstream target genes was also decreased, which was related to hyper-methylation of the HIF1\u03b1 promoter. Finally, increased HIF1\u03b1 protein expression reversed the inhibitory effect of TET1 knockdown on the migration and invasion of JEG3 cells exposed to 3% oxygen. These data show that hypoxia-induced TET1 expression facilitates trophoblast cell migration and invasion through the HIF1\u03b1 signaling pathway, which plays an important role during placentation.<\/jats:p>","DOI":"10.1038\/s41598-017-07560-7","type":"journal-article","created":{"date-parts":[[2017,8,8]],"date-time":"2017-08-08T15:11:18Z","timestamp":1502205078000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Hypoxia-induced TET1 facilitates trophoblast cell migration and invasion through HIF1\u03b1 signaling pathway"],"prefix":"10.1038","volume":"7","author":[{"given":"Jingping","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwen","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julei","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinting","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhui","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,14]]},"reference":[{"key":"7560_CR1","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S0002-9378(87)80371-X","volume":"157","author":"J Hustin","year":"1987","unstructured":"Hustin, J. & Schaaps, J. P. Echographic [corrected] and anatomic studies of the maternotrophoblastic border during the first trimester of pregnancy. Am J Obstet Gynecol \n                           157, 162\u2013168 (1987).","journal-title":"Am J Obstet Gynecol"},{"key":"7560_CR2","doi-asserted-by":"crossref","unstructured":"Lyall, F. Priming and remodelling of human placental bed spiral arteries during pregnancy - A Review. Placenta \n                           26 (2005).","DOI":"10.1016\/j.placenta.2005.02.010"},{"issue":"Suppl A","key":"7560_CR3","doi-asserted-by":"publisher","first-page":"S63","DOI":"10.1053\/plac.2001.0642","volume":"22","author":"GJ Burton","year":"2001","unstructured":"Burton, G. J. & Caniggia, I. Hypoxia: implications for implantation to delivery-a workshop report. 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