{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T20:43:47Z","timestamp":1781988227589,"version":"3.54.5"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Research Project of Changzhou Medical Center of Nanjing Medical University","award":["CMCM202203"],"award-info":[{"award-number":["CMCM202203"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2705400"],"award-info":[{"award-number":["2023YFC2705400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301897"],"award-info":[{"award-number":["82301897"]}],"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":["82030040"],"award-info":[{"award-number":["82030040"]}],"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":["82171653"],"award-info":[{"award-number":["82171653"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Recurrent spontaneous miscarriage is one of the complications during pregnancy. However, the pathogenesis of recurrent spontaneous miscarriage is far from fully elucidated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Since the endocytic pathway is crucial for cellular homeostasis, our study aimed to explore the roles of endocytic recycling, especially EH domain containing 1, a member of the endocytic recycling compartment, in recurrent spontaneous miscarriage.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Study Design<\/jats:title>\n                  <jats:p>We first investigated the expression of the endocytic pathway member EH domain containing 1 in villi from the normal and recurrent spontaneous miscarriage groups. Then, we performed ribonucleic acid sequencing and experiments in villi, HTR8 cells and BeWo cells to determine the mechanisms by which EH domain containing 1\u2013induced recurrent spontaneous miscarriage. Finally, placenta\u2013specific EH domain containing 1\u2013overexpressing mice were generated to investigate the recurrent spontaneous miscarriage phenotype in vivo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>EH domain containing 1 was expressed in extravillous trophoblasts and syncytiotrophoblast in the villi. Compared with the control group, recurrent spontaneous miscarriage patients expressed higher EH domain containing 1. A high level of EH domain containing 1 decreased proliferation, promoted apoptosis, and reduced the migration and invasion of HTR8 cells by activating the TGF\u03b2 receptor 1-SMAD2\/3 signaling pathway. The TGF\u03b2 receptor 1 antagonist LY3200882 partially reversed the EH domain containing 1 overexpression-induced changes in the cell phenotype. Besides, a high level of EH domain containing 1 also induced abnormal syncytialization, which disturbed maternal\u2013fetal material exchanges. In a mouse model, placenta-specific overexpression of EH domain containing 1 led to the failure of spiral artery remodeling, excessive syncytialization, and miscarriage.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Increased expression of EH domain containing 1 impaired the invasion of extravillous trophoblasts mediated by the TGF\u03b2 receptor 1-SMAD2\/3 signaling pathway and induced abnormal syncytialization of syncytiotrophoblast, which is at least partially responsible for recurrent spontaneous miscarriage.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/biolre\/ioae110","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T05:51:37Z","timestamp":1721022697000},"page":"1235-1248","source":"Crossref","is-referenced-by-count":2,"title":["Increased EHD1 in trophoblasts causes RSM by activating TGF\u03b2 signaling"],"prefix":"10.1093","volume":"111","author":[{"given":"Xing","family":"Wu","sequence":"first","affiliation":[{"name":"Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University Reproductive Medicine Centre, , No. 53 Zhongshan North Road, Nanjing 210008, People\u2019s Republic of","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayan","family":"Shen","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University Reproductive Medicine Centre, , No. 53 Zhongshan North Road, Nanjing 210008, People\u2019s Republic of","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjin","family":"Liu","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University Reproductive Medicine Centre, , No. 53 Zhongshan North Road, Nanjing 210008, People\u2019s Republic of","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Kang","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Nanjing University Medical School Reproductive Medicine Center, Nanjing Drum Tower Hospital, , No. 53 Zhongshan North Road, Nanjing 210008, People\u2019s Republic of","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingshun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nanjing Medical University NHC Key Laboratory of Antibody Technique, Jiangsu Key Laboratory of Pathogen Biology, Department of Immunology, , No. 101 Longmian Avenue, Nanjing 211166, People\u2019s Republic of","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Cai","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Nanjing University Medical School Reproductive Medicine Center, Nanjing Drum Tower Hospital, , No. 53 Zhongshan North Road, Nanjing 210008, People\u2019s Republic of","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhen","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Nanjing University Medical School Reproductive Medicine Center, Nanjing Drum Tower Hospital, , No. 53 Zhongshan North Road, Nanjing 210008, People\u2019s Republic of","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guijun","family":"Yan","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University Reproductive Medicine Centre, , No. 53 Zhongshan North Road, Nanjing 210008, People\u2019s Republic of","place":["China"]},{"name":"Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University Reproductive Medicine Centre, , No. 53 Zhongshan North Road, Nanjing 210008, People\u2019s Republic of","place":["China"]},{"name":"The Affiliated Hospital of Nanjing University Medical School Reproductive Medicine Center, Nanjing Drum Tower Hospital, , No. 53 Zhongshan North Road, Nanjing 210008, People\u2019s Republic of","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Nanjing University Medical School Reproductive Medicine Center, Nanjing Drum Tower Hospital, , No. 53 Zhongshan North Road, Nanjing 210008, People\u2019s Republic of","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University Reproductive Medicine Centre, , No. 53 Zhongshan North Road, Nanjing 210008, People\u2019s Republic of","place":["China"]},{"name":"The Affiliated Hospital of Nanjing University Medical School Reproductive Medicine Center, Nanjing Drum Tower Hospital, , 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