{"id":222,"title":"Revealing the Action Mechanism of WISP2 in Miscarriage Based Multi-Omic Analysis and Experimental Validation","title_zh":"多组学分析与实验验证揭示WISP2在复发性流产中的作用","url":"https://pubmed.ncbi.nlm.nih.gov/42989500","doi":"10.1111/cbdd.70423","pmid":"42989500","journal":"Chem Biol Drug Des","kind":"paper","lang":"en","published_at":"2026-11-01T00:00:00+00:00","fetched_at":"2026-11-08T03:44:00+00:00","authors":["Leng Z","Yan B","Wang F","Bian X","Huang Y","Lv H","Jiang Z","Sun X"],"primary_topic":"early-pregnancy","topics":[{"slug":"omics-methods","score":5.0,"hits":["multi-omic","single-cell","single-cell rna"]},{"slug":"early-pregnancy","score":4.0,"hits":["miscarriage","recurrent miscarriage"]},{"slug":"endometrium","score":2.0,"hits":["trophoblast","trophoblast invasion"]}],"topic_score":5.0,"preference_score":10.0,"preference_labels":["多组学整合分析（任意生殖对象）"],"llm_score":71.0,"final_score":81.0,"score_dims":{"novelty":70,"rigor":65,"impact":68,"relevance":90,"translation":60},"recommend_reason":"将单细胞转录组与组织及细胞功能验证结合，聚焦RM中滋养层WISP2，主题核心且提供一定机制线索；但样本与体外证据有限，摘要中表达方向表述不够一致，适合作为RM机制研究的浏览文献。","keywords":["WISP2","复发性流产","滋养层细胞","单细胞RNA测序","EMT","ERK通路"],"selected":1,"story_id":236,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-uterus-pregnancy","source_name":"PubMed · 内膜/植入/早孕","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":null,"journal_tier":"unknown","journal_if":null,"is_mock":false,"summary_zh":"该研究对复发性流产（RM）与正常对照的绒毛组织进行单细胞RNA测序，锁定合体滋养层/绒毛外滋养层（SCT/EVT）中的WISP2，并在20例RM与20例对照的绒毛膜样本中用qRT-PCR、Western blot和免疫组化验证；同时在HTR-8细胞过表达WISP2，开展增殖、迁移与侵袭实验。结果显示RM中WISP2表达异常，体外可促进上皮样表型并伴ERK通路激活，抑制滋养层侵袭与EMT，提示其可能参与RM发病，但仍需体内验证。","summary":"Recurrent miscarriage (RM) is a major unresolved issue in reproductive medicine. Although WISP2 is known to participate in multiple cellular processes, its function in trophoblast biology and pregnancy maintenance remains unknown. We performed single-cell RNA sequencing on chorionic villus tissues from RM patients and normal controls to identify cell-type-specific transcriptional alterations, which led to the identification of WISP2 as a candidate gene in the SCT/EVT subpopulation. Fetal membrane samples (chorion) were obtained from Qingdao Women and Children's Hospital's Surgical Outpatient Department: 20 RM patients and 20 healthy controls. Using qRT-PCR, Western blot, and immunohistochemistry to detect gene and protein expression. HTR-8 cells were used to construct WISP2 overexpressing cells, and MTT, wound healing and Transwell experiments were performed for functional experiments. Eleven cell classes in the sample were demonstrated by single-cell analysis. Among these cells were DSCs and SCT/extravillous trophoblasts (EVT). The level of WISP2 is low in SCT/EVT cells from RM patients. In chorionic villus tissues, both WISP2 and E-cadherin were significantly upregulated in the RM group relative to the control group (all p 0.05), suggesting that WISP2 promotes an epithelial-like phenotype accompanied by ERK pathway activation. In summary, WISP2 is dysregulated in RM and suppresses trophoblast invasion and EMT in vitro, suggesting a potential role in RM pathogenesis, though in vivo validation is required.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}