{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T21:27:40Z","timestamp":1783718860864,"version":"3.55.0"},"reference-count":62,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81671488"],"award-info":[{"award-number":["81671488"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871189"],"award-info":[{"award-number":["81871189"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071675"],"award-info":[{"award-number":["82071675"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U21A20346"],"award-info":[{"award-number":["U21A20346"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171662"],"award-info":[{"award-number":["82171662"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pre\u2010eclampsia (PE) is deemed an ischemia\u2010induced metabolic disorder of the placenta due to defective invasion of trophoblasts during placentation; thus, the driving role of metabolism in PE pathogenesis is largely ignored. Since trophoblasts undergo substantial glycolysis, this study aimed to investigate its function and regulatory mechanism by AMPK in PE development. Metabolomics analysis of PE placentas was performed by gas chromatography\u2013mass spectrometry (GC\u2013MS). Trophoblast\u2010specific <jats:italic>AMPK\u03b11<\/jats:italic>\u2010deficient mouse placentas were generated to assess morphology. A mouse PE model was established by Reduced Uterine Perfusion Pressure, and placental AMPK was modulated by nanoparticle\u2010delivered A769662. Trophoblast glucose uptake was measured by 2\u2010NBDG and 2\u2010deoxy\u2010<jats:sc>d<\/jats:sc>\u2010[<jats:sup>3<\/jats:sup>H] glucose uptake assays. Cellular metabolism was investigated by the Seahorse assay and GC\u2013MS.PE complicated trophoblasts are associated with AMPK hyperactivation due not to energy deficiency. Thereafter, AMPK activation during placentation exacerbated PE manifestations but alleviated cell death in the placenta. AMPK activation in trophoblasts contributed to GLUT3 translocation and subsequent glucose metabolism, which were redirected into gluconeogenesis, resulting in deposition of glycogen and accumulation of phosphoenolpyruvate; the latter enhanced viability but compromised trophoblast invasion. However, ablation of AMPK in the mouse placenta resulted in decreased glycogen deposition and structural malformation. These data reveal a novel homeostasis between invasiveness and viability in trophoblasts, which is mechanistically relevant for switching between the \u2018go\u2019 and \u2018grow\u2019 cellular programs.<\/jats:p>","DOI":"10.1111\/cpr.13358","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T18:48:34Z","timestamp":1670525314000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["<scp>AMPK<\/scp> regulates homeostasis of invasion and viability in trophoblasts by redirecting glucose metabolism: Implications for pre\u2010eclampsia"],"prefix":"10.1111","volume":"56","author":[{"given":"Ping","family":"Xu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education\u2010International Collaborative Laboratory of Reproduction and Development Chongqing Medical University  Chongqing China"},{"name":"Biochemistry and Molecular Biology University of Texas McGovern Medical School  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangxi","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education\u2010International Collaborative Laboratory of Reproduction and Development Chongqing Medical University  Chongqing China"},{"name":"Department of Stem Cell Transplantation and Cell Therapy MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiujiang","family":"Liao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education\u2010International Collaborative Laboratory of Reproduction and Development Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education\u2010International Collaborative Laboratory of Reproduction and Development Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yike","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baozhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9987-4223","authenticated-orcid":false,"given":"Mark D.","family":"Kilby","sequence":"additional","affiliation":[{"name":"Institute of Metabolism and System Research University of Birmingham  Edgbaston UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijia","family":"Fu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education\u2010International Collaborative Laboratory of Reproduction and Development Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Women and Children's Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumei","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education\u2010International Collaborative Laboratory of Reproduction and Development Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liling","family":"Xiong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education\u2010International Collaborative Laboratory of Reproduction and Development Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyao","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education\u2010International Collaborative Laboratory of Reproduction and Development Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huili","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education\u2010International Collaborative Laboratory of Reproduction and Development Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education\u2010International Collaborative Laboratory of Reproduction and Development Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education\u2010International Collaborative Laboratory of Reproduction and Development Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingli","family":"Han","sequence":"additional","affiliation":[{"name":"Ministry of Education\u2010International Collaborative Laboratory of Reproduction and Development Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education\u2010International Collaborative Laboratory of Reproduction and Development Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rufei","family":"Gao","sequence":"additional","affiliation":[{"name":"Laboratory of Reproductive Biology, School of Public Health and Management Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Fu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education\u2010International Collaborative Laboratory of Reproduction and Development Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujun","family":"Fan","sequence":"additional","affiliation":[{"name":"Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Qi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education\u2010International Collaborative Laboratory of Reproduction and Development Chongqing Medical University  Chongqing China"},{"name":"Department of Obstetrics Women and Children's Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip N.","family":"Baker","sequence":"additional","affiliation":[{"name":"College of Life Sciences University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0828-2674","authenticated-orcid":false,"given":"Chao","family":"Tong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education\u2010International Collaborative Laboratory of Reproduction and Development Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-121808-102149"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1706546114"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3787"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.09.021"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00011.2008"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06504"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2016.0252"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2014.0092"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.315"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00251-9"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2012.07.001"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2004.04.006"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-016-1202-4"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118036"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000055314"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(00)00371-3"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000008557"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00523.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-118-4-1567"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0155426"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00268.2014"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00117.2012"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.00055"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029236"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.22904"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn400334y"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvn054"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.953208"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2015.08.014"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-2118"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/det060"},{"issue":"19","key":"e_1_2_10_33_1","first-page":"5410","article-title":"Endostatin inhibits endothelial and tumor cellular invasion by blocking the activation and catalytic activity of matrix metalloproteinase","volume":"60","author":"Kim YM","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3311"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1159\/000492995"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.05.005"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20981"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00662-09"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.051"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2598"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.630194"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2015.10.004"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.566927"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2249"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1200094"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2676"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2017.80"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/70293"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13079"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-16-0031"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2011.07.036"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00200.2012"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-019-01746-4"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07709"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah5582"},{"issue":"5","key":"e_1_2_10_56_1","first-page":"359","article-title":"Mediation of AMP kinase in the increase of glucose uptake in L6 cells induced by activation of imidazoline I\u20102 receptors","volume":"45","author":"Yang TT","year":"2013","journal-title":"Horm Metab Res"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.7.1649"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14655"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90388.2008"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2011.09.014"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2012.07.014"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2017.01.130"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.20422"}],"container-title":["Cell Proliferation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.13358","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cpr.13358","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.13358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T15:04:54Z","timestamp":1692457494000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cpr.13358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,8]]},"references-count":62,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1111\/cpr.13358"],"URL":"https:\/\/doi.org\/10.1111\/cpr.13358","archive":["Portico"],"relation":{},"ISSN":["0960-7722","1365-2184"],"issn-type":[{"value":"0960-7722","type":"print"},{"value":"1365-2184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,8]]},"assertion":[{"value":"2022-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13358"}}