{"doi":"10.1210/clinem/dgaa357","title":"Trophoblast H2S Maintains Early Pregnancy via Regulating Maternal-Fetal Interface Immune Hemostasis","abstract":"CONTEXT: Dysregulated immune hemostasis occurs in unexplained recurrent spontaneous abortion (URSA). Synthesized by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), hydrogen sulfide (H2S) promotes regulatory T-cell differentiation and regulates immune hemostasis; yet, its role in URSA is elusive. OBJECTIVE: To determine if H2S plays a role in early pregnancy and if dysregulated H2S signaling results in recurrent spontaneous abortion. DESIGN: 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 × DBA/2 mice were treated with CBS and CSE inhibitors or H2S donors to determine the role of H2S in early pregnancy in vivo. RESULTS: 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-κB-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. CONCLUSION: CBS/H2S signaling maintains early pregnancy, possibly via regulating maternal-fetal interface immune hemostasis, offering opportunities for H2S-based immunotherapies for URSA.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2020,"id":103181,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9649,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":503011,"name":"Tonghui Xu","orcid":"0000-0003-0652-9370","position":1,"is_corresponding":false},{"id":291745,"name":"Yan Li","orcid":"0000-0003-1813-8115","position":2,"is_corresponding":false},{"id":383972,"name":"Wenfu Wang","orcid":"0000-0002-3963-1649","position":3,"is_corresponding":false},{"id":503947,"name":"Chunzi Lyu","orcid":null,"position":4,"is_corresponding":false},{"id":503012,"name":"Dan Luo","orcid":"0000-0001-7105-4485","position":5,"is_corresponding":false},{"id":503013,"name":"Qiuhong Yang","orcid":"0000-0003-3222-7915","position":6,"is_corresponding":false},{"id":503014,"name":"Nannan Ning","orcid":"0000-0003-1347-5171","position":7,"is_corresponding":false},{"id":271252,"name":"Zi‐Jiang Chen","orcid":"0000-0001-6637-6631","position":8,"is_corresponding":false},{"id":503015,"name":"Junhao Yan","orcid":"0000-0002-7110-8698","position":9,"is_corresponding":false},{"id":476920,"name":"Dong‐bao Chen","orcid":"0000-0002-1067-6018","position":10,"is_corresponding":false},{"id":503016,"name":"Jingxin Li","orcid":"0000-0001-7370-703X","position":11,"is_corresponding":false},{"id":503946,"name":"Banqin Wang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-18T22:42:17.920911Z","pmid":"32506120","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}