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Here, we observed that thrombospondin-1, an adhesive glycoprotein, was significantly downregulated in endometrial decidual cells from patients with unexplained recurrent spontaneous abortion. The immortalized human endometrial stromal cell line was used to investigate the possible THBS1-mediated regulation of decidualization. In vitro experiments found that the expression level of THBS1 increased with the normal decidualization process. Knockdown of THBS1 could decrease the expression levels of prolactin and insulin-like growth factor binding protein-1, two acknowledged human decidualization markers, whereas THBS1 overexpression could reverse these effects. The RNA sequencing results demonstrated that the extracellular regulated protein kinases signaling pathway was potentially affected by the knockdown of THBS1. We further confirmed that the regulation of THBS1 on decidualization was achieved through the ERK signaling pathway by the treatment of inhibitors. Moreover, knockdown of THBS1 in pregnant mice could impair decidualization and result in an increased fetus resorption rate. Altogether, our study demonstrated a crucial role of THBS1 in the pathophysiological process of unexplained recurrent spontaneous abortion and provided some new insights into the research of pregnancy-related complications.<\/jats:p>","DOI":"10.1093\/biolre\/ioae079","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T07:24:30Z","timestamp":1716449070000},"page":"448-462","source":"Crossref","is-referenced-by-count":2,"title":["Decreased thrombospondin-1 impairs endometrial stromal decidualization in unexplained recurrent spontaneous abortion"],"prefix":"10.1093","volume":"111","author":[{"given":"Jianing","family":"Hu","sequence":"first","affiliation":[{"name":"School of Medicine, The International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University , No. 910 Hengshan Road, Xuhui District, Shanghai 200030 , China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases , No. 910 Hengshan Road, Xuhui District, Shanghai 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Shanghai 200030 , China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases , No. 910 Hengshan Road, Xuhui District, Shanghai 200030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomiao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences , No. 106 Zhongshan Second Road, Yuexiu District, Guangzhou 510080 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cailian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Automation, Shanghai Jiao Tong University, Key Laboratory of System Control and Information Processing, Ministry of Education of China , No. 800 Dongchuan Road, Minhang District, Shanghai 201100 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lin","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong 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