{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:35:20Z","timestamp":1791974120834,"version":"4.4.0"},"reference-count":73,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2020,6,7]],"date-time":"2020-06-07T00:00:00Z","timestamp":1591488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["#81771601"],"award-info":[{"award-number":["#81771601"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFC1302203"],"award-info":[{"award-number":["2016YFC1302203"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFC1000202"],"award-info":[{"award-number":["2016YFC1000202"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFC1002804"],"award-info":[{"award-number":["2018YFC1002804"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 HL70562"],"award-info":[{"award-number":["RO1 HL70562"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 HD097498"],"award-info":[{"award-number":["R21 HD097498"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Dysregulated immune hemostasis occurs in unexplained recurrent spontaneous abortion (URSA). Synthesized by cystathionine \u03b2-synthase (CBS) and cystathionine \u03b3-lyase (CSE), hydrogen sulfide (H2S) promotes regulatory T-cell differentiation and regulates immune hemostasis; yet, its role in URSA is elusive.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To determine if H2S plays a role in early pregnancy and if dysregulated H2S signaling results in recurrent spontaneous abortion.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>First trimester placenta villi and decidua were collected from normal and URSA pregnancies. Protein expression was examined by immunohistochemistry and immunoblotting. Human trophoblast HTR8\/SVneo and JEG3 cells were treated with H2S donors; HTR8\/SVneo cells were transfected with CBS ribonucleic acid interference (RNAi) or complementary deoxyribonucleic acid. Cell migration and invasion were determined by transwell assays; trophoblast transcriptomes were determined by RNA sequencing (RNA-seq). Wild-type, CBS-deficient, and CBA\/J \u00d7 DBA\/2 mice were treated with CBS and CSE inhibitors or H2S donors to determine the role of H2S in early pregnancy in vivo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>CBS and CSE proteins showed cell-specific expressions, but only CBS decreased in the villous cytotrophoblast in URSA versus normal participants. H2S donors promoted migration and invasion and MMP-2 and VEGF expression in human placenta trophoblast cells that contain SV40 viral deoxyribonucleic acid sequences (HTR8\/SVneo) and human placenta trophoblast cells (JEG3 cells), similar to forced CBS expression in HTR8\/SVneo cells. The CBS-responsive transcriptomes in HTR8\/SVneo cells contained differentially regulated genes (ie, interleukin-1 receptor and prostaglandin-endoperoxide synthase 2) that are associated with nuclear factor-\u03baB-mediated inflammatory response. In vivo, dysregulated CBS\/H2S signaling significantly increased embryonic resorption and decidual T-helper 1\/T-helper 2 imbalance in mice, which was partially rescued by H2S donors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>CBS\/H2S signaling maintains early pregnancy, possibly via regulating maternal-fetal interface immune hemostasis, offering opportunities for H2S-based immunotherapies for URSA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa357","type":"journal-article","created":{"date-parts":[[2020,6,7]],"date-time":"2020-06-07T17:14:32Z","timestamp":1591550072000},"page":"e4275-e4289","source":"Crossref","is-referenced-by-count":24,"title":["Trophoblast H2S Maintains Early Pregnancy via Regulating Maternal-Fetal Interface Immune Hemostasis"],"prefix":"10.1210","volume":"105","author":[{"given":"Banqin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonghui","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Research Center, Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunzi","family":"Lyu","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuhong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China"},{"name":"Department of Obstetrics and Gynecology, Jinan Maternity and Child Care Hospital, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Jiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhao","family":"Yan","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1067-6018","authenticated-orcid":false,"given":"Dong-bao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, 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