{"doi":"10.1101/2025.09.18.677237","title":"Nicotinamide opposes ET-1’s adverse effect on uterine decidualization via EDNRB","abstract":"Abstract Endothelin-1 is involved in pathogenesis of preeclampsia. Mice ( Edn1 H/+ ) having excess endothelin-1 developed preeclampsia-like phenotypes during pregnancy in a maternal genotype-dependent manner. Here, we investigate whether decidualization is impaired in Edn1 H/+ dams, and whether nicotinamide (a potent inhibitor of endothelin-1) exerts beneficial effect. We compared implantation sites between wild type (WT) and Edn1 H/+ dams with or without nicotinamide treatment. Implantation sites of Edn1 H/+ dams exhibited abnormal ectoplacental cone and sinusoids with reduced vascular density in mesometrial regions of deciduae. There was more VEGF in decidua of Edn1 H/+ dams than WT dams. Markers of decidualization were decreased in Edn1 H/+ dams. Nicotinamide supplementation corrected this abnormality. During differentiation (decidualization) of cultured human endometrial stomal cells, endothelin-1 impaired the upregulated expression of decidualization markers. The endothelin-1’s effect was reversed by nicotinamide. These results show nicotinamide counteracts ET-1’s detrimental effects on endometrial decidualization and has potential to improve embryo implantation and subsequent pregnancy outcomes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":575393,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1323192,"name":"Qing Ma","orcid":"0009-0007-3505-688X","position":1,"is_corresponding":false},{"id":1441081,"name":"Meitong Chen","orcid":null,"position":2,"is_corresponding":false},{"id":411206,"name":"Yukako Kayashima","orcid":"0000-0003-3415-9135","position":3,"is_corresponding":false},{"id":1248713,"name":"Jiayi Zhou","orcid":"0009-0009-7301-2698","position":4,"is_corresponding":false},{"id":304473,"name":"Balaji M. Rao","orcid":"0000-0001-5695-8953","position":5,"is_corresponding":false},{"id":647604,"name":"Jessica L. Bowser","orcid":"0000-0003-0655-7769","position":6,"is_corresponding":false},{"id":433247,"name":"Xianwen Yi","orcid":null,"position":7,"is_corresponding":false},{"id":412512,"name":"Nobuyo Maeda-Smithies","orcid":null,"position":8,"is_corresponding":false},{"id":1092469,"name":"Feng Li","orcid":"0000-0002-6779-5077","position":9,"is_corresponding":false},{"id":1441227,"name":"Y. H. Wang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T02:57:48.486077Z","pmid":"41000910","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":[]}