Yifeng Zhang , Dongjie Wang , Xiaomei Wu , Ting Zhao , Ming He , Yunyu He , Chunmei Meng
{"title":"Targeting the lncRNA GAS5/TLR4/NLRP3 signaling cascade inhibits endometrial stromal cell pyroptosis and prevents the progression of intrauterine adhesions","authors":"Yifeng Zhang , Dongjie Wang , Xiaomei Wu , Ting Zhao , Ming He , Yunyu He , Chunmei Meng","doi":"10.1016/j.jri.2025.104450","DOIUrl":"10.1016/j.jri.2025.104450","url":null,"abstract":"<div><div>Intrauterine adhesion (IUA) poses a serious threat to women's health, and its specific pathogenesis has not yet been elucidated. Our study found through high-throughput sequencing that differentially expressed genes of the endometrial tissues from healthy individuals or IUA patients were enriched in the toll-like receptor (TLR), nuclear factor-kappa B (NF-kB), and nucleotide-binding oligomerization domain-like receptor (NLR) signaling pathways. Meanwhile, we observed that compared to the controls, long non-coding RNA (lncRNA) growth arrest-specific transcripts 5 (GAS5) was significantly upregulated in the endometrial tissue of IUA patients and scratching/lipopolysaccharide (LPS)-induced IUA model mice. Subsequently, results from the functional verification assay, including hematoxylin-eosin staining, enzyme-linked immunosorbent assay, and western blot, showed that knockdown of GAS5 improved endometrial injury and uterine adhesions, decreased the levels of TIMP1, α-SMA, Vimentin, and COL1A1, but elevated MMP9 level to reduce excessive accumulation of extracellular matrix (ECM), and inhibited the expression of NLRP3, cleaved caspase-1, GSDMD, and nuclear p65 to ameliorate pyroptosis in IUA model mice. As confirmed by bioinformatics analysis and dual luciferase reporter gene system, GAS5 sponged microRNA (miR)-205–5p to upregulate TLR4, further activating the NF-kB and NLRP3 signaling in endometrial stromal cells (ESCs). The <em>in vitro</em> functional recovery experiments suggested that GAS5 knockdown alleviated LPS-induced activation of the NF-kB and NLRP3 signaling, pyroptotic cell death, and ECM deposition in ESCs, which was counteracted by overexpressing TLR4 and NLRP3. In a word, our study proved that targeting the GAS5/TLR4/NLRP3 signaling cascade inhibits ESCs pyroptosis and prevents the progression of IUA, providing promising therapeutic strategies for IUA disease.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104450"},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruting Zhang , Hanxin Lv , Jinghua Liu , Jiashan Yin , Shuang Wu , Yuyang Xie , Huihui Xing , Rui Wang , Zefan Zhao , Bimin Shi , Xiaoqin Yang , Shangshang Gao
{"title":"The impact of MTHFR and VDR polymorphisms on endometriosis susceptibility: Insights from a systematic review and meta-analysis","authors":"Ruting Zhang , Hanxin Lv , Jinghua Liu , Jiashan Yin , Shuang Wu , Yuyang Xie , Huihui Xing , Rui Wang , Zefan Zhao , Bimin Shi , Xiaoqin Yang , Shangshang Gao","doi":"10.1016/j.jri.2025.104449","DOIUrl":"10.1016/j.jri.2025.104449","url":null,"abstract":"<div><div>The <em>VDR</em> and <em>MTHFR</em> polymorphisms have been linked to many gynecological and obstetrical diseases. However, there is still a pressing need for a systematic review and meta-analysis to synthesize the current evidence on the association between these variants and endometriosis risk. English and Chinese literature databases were systematically retrieved to find relevant research published up to August 1, 2024. The meta-analytic calculations were implemented in the R language 4.4.1 environment. The odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were estimated to assess the magnitude of the effect. In total, 26 datasets comprising 9300 subjects were included. The pooled estimate demonstrated a significant association between the <em>MTHFR</em> C677T polymorphism and endometriosis susceptibility in the allele model (OR: 1.41, 95 % CI: 1.07–1.86, <em>P</em> = 0.01), homozygote model (OR: 2.09, 95 % CI: 1.56–2.79, <em>P</em> < 0.01), dominant model (OR: 1.48, 95 % CI: 1.06–2.07, <em>P</em> = 0.02), and recessive model (OR: 1.81, 95 % CI: 1.38–2.37, <em>P</em> < 0.01). However, the meta-analysis for the <em>MTHFR</em> A1298C polymorphism and the <em>VDR Fok</em>I, <em>Taq</em>I, <em>Apa</em>I, and <em>Bsm</em>I polymorphic variants did not find statistical significance. In conclusion, this meta-analysis suggests that the <em>MTHFR</em> C677T polymorphism might play a role in developing endometriosis disease. Meanwhile, further large-scale validations that consider multiple factors are warranted to confirm this finding.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104449"},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yi Jiang , Qingxia You , Fangxiang Mu , Shiqing Xiang , Nian Zhang
{"title":"Endoplasmic reticulum stress and unfolded protein response play roles in recurrent pregnancy loss: A bioinformatics study","authors":"Yi Jiang , Qingxia You , Fangxiang Mu , Shiqing Xiang , Nian Zhang","doi":"10.1016/j.jri.2025.104446","DOIUrl":"10.1016/j.jri.2025.104446","url":null,"abstract":"<div><div>This study aims to explore whether endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) processes could be potential targets for preventive, diagnostic, and therapeutic for recurrent pregnancy loss (RPL). RPL datasets GSE165004 and GSE26787 were sourced from the GEO database, and ERS- and UPR-related gene sets were obtained from the MsigDB database. After differentially expressed genes (DEGs) identification, key genes were screened from intersecting DEGs in RPL-ERS and RPL-UPR datasets. The z-score algorithm was conducted to obtain phenotype scores. Functional enrichment and machine learning analyses were performed to assess gene function and diagnostic value evaluation. Interaction networks were conducted to investigate upstream regulated relationships of the key genes. Immune infiltration and single-cell RNA sequencing (scRNA-seq) were assessed to explore ERS and UPR functions at the cellular level. Totally 25 key genes RPL-ERS DEGs and 16 key genes RPL-UPR DEGs were identified. Among them, six key genes (NFYB, EXOSC2, UBQLN2, RNF139, DERL1, and FBXO27) were validated to show consistent expression trends in both RPL datasets. Functional enrichment highlighted their involvement in the immunity of RPL. Machine learning indicated the significant diagnostic value of these validated genes for RPL, with an accuracy rate of > 80 %. scRNA-seq analysis revealed elevated ERS and UPR expressions in monocytes/macrophages in RPL samples. In conclusion, ERS and UPR processes are associated with RPL occurrences, and were mainly upregulated in monocytes/macrophages within RPL samples. ERS and UPR processes may serve as potential targets for the prevention, diagnosis, and treatment of RPL.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104446"},"PeriodicalIF":2.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lan Luo , Man Luo , Yanli Peng , Donghong Ning , Qiuman Zheng , Qin Cao , Ziting Ouyang
{"title":"METTL14-mediated m6A modification regulates endometrial receptivity by inhibiting SLC39A14","authors":"Lan Luo , Man Luo , Yanli Peng , Donghong Ning , Qiuman Zheng , Qin Cao , Ziting Ouyang","doi":"10.1016/j.jri.2025.104447","DOIUrl":"10.1016/j.jri.2025.104447","url":null,"abstract":"<div><div>Endometrial receptivity is a complex process that prepares the endometrium for embryo implantation. Inadequate endometrial receptivity is one cause of implantation failure. This study aimed to explore the impact of METTL14-mediated m<sup>6</sup>A modification of SLC39A14 on endometrial stromal cells (ESCs). ESCs were transfected and subjected to CCK-8 viability assay, EdU proliferation assay, and flow cytometry cell cycle and apoptosis analyses. Autophagy-related proteins LC3, p62, and Beclin-1 were detected through western blotting. RIP was used to detect the interaction between METTL14 protein and SLC39A14 mRNA. Me-RIP was used to measure the m<sup>6</sup>A level of SLC39A14. Actinomycin D was used to assess the stability of SLC39A14 mRNA. METTL14 overexpression or SLC39A14 knockdown enhanced viability, promoted proliferation and cell cycle progression, restrained apoptosis, reduced LC3II/LC3I and Beclin-1 levels, and increased p62 expression in ESCs. METTL14 bound to SLC39A14 mRNA and increased SLC39A14 m<sup>6</sup>A modification, reducing SLC39A14 mRNA stability and SLC39A14 protein expression. SLC39A14 overexpression eliminated the effect of METTL14 overexpression on ESCs. In conclusion, METTL14 promotes proliferation and inhibits apoptosis and autophagy activation in ESCs by inhibiting SLC39A14.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104447"},"PeriodicalIF":2.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chongying Zhu , Bingquan Zhu , Shouying Xu , Lin Li , Yanhua Song , Chao Tang
{"title":"ARID1A: Multiple functions in human pregnancy","authors":"Chongying Zhu , Bingquan Zhu , Shouying Xu , Lin Li , Yanhua Song , Chao Tang","doi":"10.1016/j.jri.2025.104448","DOIUrl":"10.1016/j.jri.2025.104448","url":null,"abstract":"<div><div>AT-rich interacting domain containing respectively protein 1 A (ARID1A), a key member of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, has been shown to play an important role in various physiological processes and diseases including female reproductive tumors, such as ovarian cancer and breast cancer. In addition to the studies regarding ARID1A expression and function in cancer, recent findings elucidate its important role in maintaining normal tissue homeostasis and cell differentiation by controlling chromatin remodeling and transcription factors recruitment. In the context of human pregnancy, ARID1A has been implicated in several pregnancy-related complications, including gestational diabetes, preeclampsia, and intrauterine growth restriction. This review examines the current research on the role of ARID1A in pregnancy, highlighting its potential as a biomarker and therapeutic target for these complications. Understanding the involvement of ARID1A in placental function and pregnancy-related disorders may provide valuable insights for the development of novel diagnostic and therapeutic strategies.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104448"},"PeriodicalIF":2.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143153086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L.J. van ’t Hof * , J.M. Kapsenberg , J.J.M. Drabbels , L.E. van der Meeren , D.L. Roelen , M. Eikmans , M.L.P. van der Hoorn
{"title":"NON-INVASIVE FETAL HLA TYPING ON ISOLATED TROPHOBLASTS FROM CERVICAL SMEARS IN EARLY PREGNANCY","authors":"L.J. van ’t Hof * , J.M. Kapsenberg , J.J.M. Drabbels , L.E. van der Meeren , D.L. Roelen , M. Eikmans , M.L.P. van der Hoorn","doi":"10.1016/j.jri.2024.104362","DOIUrl":"10.1016/j.jri.2024.104362","url":null,"abstract":"","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"Article 104362"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143127967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xue Wang * , Charlotte Harms , Maria Victoria Bazzano , Yiru Wang , Maria Emilia Solano , Mariana G. Garcia , Sandra M Blois
{"title":"GALECTIN-1: A KEY REGULATOR OF OVARIAN FOLLICLE BALANCE AND ANGIOGENESIS UNDER CONTROLLED OVARIAN HYPERSTIMULATION","authors":"Xue Wang * , Charlotte Harms , Maria Victoria Bazzano , Yiru Wang , Maria Emilia Solano , Mariana G. Garcia , Sandra M Blois","doi":"10.1016/j.jri.2024.104350","DOIUrl":"10.1016/j.jri.2024.104350","url":null,"abstract":"","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"Article 104350"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M.V. Bazzano * , L. Berkout , E. Tasika , F. Weber , L. Hardardottir , W. Shi , D. Zazara , Promm M , A. Köninger , P.C. Arck , L. Bosurgi , G. Tiegs , M.E. Solano
{"title":"N-ACETYLCYSTEINE PREVENTS ACETAMINOPHEN-INDUCED SUBFERTILITY IN MICE","authors":"M.V. Bazzano * , L. Berkout , E. Tasika , F. Weber , L. Hardardottir , W. Shi , D. Zazara , Promm M , A. Köninger , P.C. Arck , L. Bosurgi , G. Tiegs , M.E. Solano","doi":"10.1016/j.jri.2024.104348","DOIUrl":"10.1016/j.jri.2024.104348","url":null,"abstract":"","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"Article 104348"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143128062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"BODY-MASS-INDEX, GESTATIONAL WEIGHT GAIN, AND VITAMIN D IN PREGNANCY: KEY FACTORS FOR PREGNANCY COMPLICATIONS AND COGNITIVE OUTCOMES IN EARLY CHILDHOOD","authors":"M. Kreuzer *, M. Albrecht, A. Diemert, P. Arck","doi":"10.1016/j.jri.2024.104366","DOIUrl":"10.1016/j.jri.2024.104366","url":null,"abstract":"","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"Article 104366"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143131279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Toffoli , G. Campisciano , A. Santin , S. Pegoraro , G. Zito , B. Spedicati , A. Balduit , F. Romano , G. Di Lorenzo , A. Mangogna , P. Tesolin , G.G. Nardone , N. Zanotta , S. Sanna , U. Kishore , G. Ricci , R. Bulla , G. Girotto , C. Agostinis
{"title":"MBL AND LECTIN PATHWAY: A DOUBLE-EDGED SWORD IN MICROBIOTA DYSBIOSIS CONNECTED TO ENDOMETRIOSIS PATHOGENESIS AND ESTROGEN SIGNALLING","authors":"M. Toffoli , G. Campisciano , A. Santin , S. Pegoraro , G. Zito , B. Spedicati , A. Balduit , F. Romano , G. Di Lorenzo , A. Mangogna , P. Tesolin , G.G. Nardone , N. Zanotta , S. Sanna , U. Kishore , G. Ricci , R. Bulla , G. Girotto , C. Agostinis","doi":"10.1016/j.jri.2024.104371","DOIUrl":"10.1016/j.jri.2024.104371","url":null,"abstract":"","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"Article 104371"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143131304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}