{"title":"Identification and Exploration of Novel B Cell Infiltration-Related Biomarkers in Endometriosis","authors":"Chunyang Zhao, Shuwei Zhang, Baosu Zhang, Hang Tian, Guojun Yan, Hongbo Zhao","doi":"10.1111/aji.70159","DOIUrl":"https://doi.org/10.1111/aji.70159","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To explore B cell infiltration-related genes in endometriosis (EM) and investigate their potential as diagnostic biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Gene expression data from the GSE51981 dataset, containing 77 endometriosis and 34 control samples, were analyzed to detect differentially expressed genes (DEGs). The xCell algorithm was applied to estimate the infiltration levels of 64 immune and stromal cell types, focusing on B cells and naive B cells. Weighted gene coexpression network analysis (WGCNA) identified B cell infiltration-related gene modules. Potential biomarker genes were screened using LASSO and SVM-RFE machine learning methods. Then, hub genes were validated in an independent GSE7305 dataset, and Pearson correlation analysis was used to assess associations between hub genes and B cell markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 4341 DEGs were screened and greenyellow module containing 349 genes were associated with infiltration characteristics of B cells in EM lesions, then 12 B cell infiltration-related genes were identified by machine learning methods. Based on the external GSE7305 dataset, four hub genes, of which NR4A1, TNS1, ZNF521, and CMPK2, were recognized as potential biomarkers of B cell infiltration in EM, and all of them were significantly upregulated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study identified and exploration four potential diagnostic biomarkers in EM. The functions of the four biomarkers and the role of B cell infiltration in EM were determined using bioinformatics analysis, providing new insights into endometriosis at the immune and molecular levels.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021787","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}
Songyuan Xiao, Yiling Ding, Ling Yu, Yali Deng, Yang Zhou, Mei Peng, Weisi Lai, Yanting Nie, Wen Zhang
{"title":"Maternal-Fetal Interface Cell Dysfunction in Patients With Preeclampsia Revealed via Single-Cell RNA Sequencing","authors":"Songyuan Xiao, Yiling Ding, Ling Yu, Yali Deng, Yang Zhou, Mei Peng, Weisi Lai, Yanting Nie, Wen Zhang","doi":"10.1111/aji.70101","DOIUrl":"https://doi.org/10.1111/aji.70101","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Preeclampsia (PE) is a leading cause of perinatal maternal and fetal mortality. Clinical and pathological studies suggest that placental and decidual cell dysfunction may contribute to this condition. However, the pathogenesis of PE remains poorly understood. Therefore, this study aims to investigate the heterogeneous changes in cell types within placental and decidual tissue isolated from cesarean sections using single-cell sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Patients included those diagnosed with PE (<i>n</i> = 3) and normal pregnancy (NP) (<i>n</i> = 3). Overall, 32 279 cells (PE: 16.575; NP: 15 704) were identified across nine cell types, including villous cytotrophoblast (VCT), syncytiotrophoblast (SCT), extravillous trophoblasts (EVT), endothelial cells, neutrophil, Hofbauer cells, T cells, dendritic cells (DC), macrophages, fibroblasts, and B cells. VCT and T cells subclusters and pseudotime were analyzed. The in vivo and in vitro experiments are focused on the invasion ability of EVT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Using gene set variation analysis (GSVA) for differential expression genes, cell-reclustering, and pseudotime analysis, the VCT in patients with PE showed a tendency to differentiate toward SCT instead of EVT. And the invasive ability of PE EVT cells was declined by decreased expression of the invasion-related gene TMEM200A. Additionally, the impaired immune environment of T-cell differentiation into CD8+T cells instead of Treg cells is the main change related to PE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest that understanding how T cell differentiation occurs in the early stage of pregnancy and how the predominantly CD8+T cell-driven immune environment influences VCT differentiation are crucial for elucidating the pathogenesis of PE.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021786","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}
Yağmur Soykan, Atiye Seda Yar Sağlam, Asiye Uğraş Dikmen, Mehmet Erdem, Ahmet Erdem
{"title":"Determination of Apoptotic Pathways in Ovarian Folicular Fluid of Infertile Patients With Endometrioma in Relation to Follicular Atresia","authors":"Yağmur Soykan, Atiye Seda Yar Sağlam, Asiye Uğraş Dikmen, Mehmet Erdem, Ahmet Erdem","doi":"10.1111/aji.70164","DOIUrl":"https://doi.org/10.1111/aji.70164","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Endometriosis is a chronic inflammatory disease that leads to pelvic pain and infertility. Recent studies have indicated that immunological, endocrine, biochemical, and genetic irregularities, along with suboptimal quality of oocytes, embryos, and the endometrial environment, significantly impact infertility associated with endometriosis. Ectopic endometrial cells in endometriosis have the capacity to avoid apoptosis. Therefore, apoptosis has supposed to play a fundamental role in the pathogenesis of endometriosis. This study aimed to investigate the association between the messenger RNA (mRNA) expression levels of apoptosis-related genes—specifically, Caspase 3 (CASP3), Caspase 8 (CASP8), Caspase 9 (CASP9), BCL-2, BCL2L1, BAX, BAK, PERFORIN, and GRANZYME B (GrB)—in follicular fluid (FF) and infertility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>The mRNA expression levels of the aforementioned genes were analyzed in FF obtained during the oocyte pick-up procedure following controlled ovarian hyperstimulation in patients undergoing in vitro fertilization due to infertility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that the presence of endometrioma correlates with altered mRNA expression levels of apoptosis-related genes in FF. Specifically, pro-apoptotic genes exhibited significantly higher expression levels (<i>p</i> < 0.05), while anti-apoptotic genes like BCL-2 and BCL2L1 were significantly lower (<i>p</i> < 0.05) as compared to controls. These results suggest a potential link between these gene expression alterations and infertility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This preliminary study provides important insights into the mRNA expression levels of genes involved in apoptosis. The findings may reveal potential therapeutic targets within the apoptosis pathway for the treatment of infertility in women with endometrioma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021847","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":"Potential Involvement of NINJ1-Mediated Plasma Membrane Rupture in Lytic Death of Granulosa Cells in PCOS","authors":"Caglar Berkel","doi":"10.1111/aji.70161","DOIUrl":"https://doi.org/10.1111/aji.70161","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012631","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}
Inha Lee, SeHee Kim, Gee Soo Jung, Yoori Shin, Min Jung Lee, Wooseok Im, Jae Hoon Lee, Young Sik Choi, SiHyun Cho
{"title":"Effects of Exosomes Derived From Eutopic Endometrial Cells in Endometriosis and the Discovery of Related Serum miRNA Biomarkers for Endometriosis","authors":"Inha Lee, SeHee Kim, Gee Soo Jung, Yoori Shin, Min Jung Lee, Wooseok Im, Jae Hoon Lee, Young Sik Choi, SiHyun Cho","doi":"10.1111/aji.70155","DOIUrl":"https://doi.org/10.1111/aji.70155","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Exosomes are secreted by most cell types and reflect the internal state of their cells of origin, playing crucial roles in the progression of various pathological conditions. Endometriosis is a chronic, estrogen-dependent inflammatory disease characterized by the ectopic presence of endometrial-like tissue outside the uterus, including in the ovaries, fallopian tubes, and peritoneal cavity. It primarily affects women of reproductive age and is often associated with infertility. Despite its high prevalence, the underlying pathogenesis remains poorly understood, and the high recurrence rate highlights the urgent need for reliable, non-invasive biomarkers for early diagnosis. Although exosomes have been implicated in the pathophysiology of endometriosis—particularly in processes such as angiogenesis and immune modulation—their role in regulating cell proliferation and apoptosis remains poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>We collected eutopic endometrial tissues from patients with endometriosis (EMS-EM) and without endometriosis (CTL-EM) and cultured to primary cells. Exosomes were extracted from EMS-EM and CTL-EM, respectively, and then treated the EMS-EM cells for 24 h.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CCK-8 and FACS assays showed that exosomes extracted from EMS-EM (EMS-Exo) treatment induced cell proliferation and reduced apoptosis. In particular, JC-1 red/green dye was significantly increased, and the mitochondrial apoptosis signal pathway was regulated by EMS-Exo treatment. The examination of protein expression identified that proliferation was induced through ERK and AKT signaling, and the mitochondrial apoptosis signaling pathway was regulated through the PI3K/AKT mechanism. miRNA array analysis showed differences in 16 miRNAs, with miR-200a-3p upregulated and 29a-3p downregulated. qRT-PCR was performed on serum exosomes for in vivo diagnosis, and significant differences were observed in five miRNAs. Through ROC curve analysis, the combination of three miRNAs was derived to show the highest diagnostic performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest that the exosome-related mechanism influences the development of endometriosis and highlights the potential of exosomes as novel diagnostic biomarkers for endometriosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012369","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":"Comment on “Prediction of Delivery Timing in Preterm Premature Rupture of Membranes: The Role of Inflammation-Related Indices”","authors":"Prajnasini Satapathy, Rachana Mehta, Ranjana Sah","doi":"10.1111/aji.70150","DOIUrl":"https://doi.org/10.1111/aji.70150","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935178","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}
Domingo V. Macinas Jr., Ourlad Alzeus G. Tantengco, Sheriah Laine M. de Paz-Silava, Ananth Kumar Kammala, Ramkumar Menon, Brandie DePaoli Taylor, Ian Kim B. Tabios
{"title":"Comparative Analysis of Vaginal Inflammatory Cytokines Among HPV-Positive and HPV-Negative Women in Manila, Philippines","authors":"Domingo V. Macinas Jr., Ourlad Alzeus G. Tantengco, Sheriah Laine M. de Paz-Silava, Ananth Kumar Kammala, Ramkumar Menon, Brandie DePaoli Taylor, Ian Kim B. Tabios","doi":"10.1111/aji.70148","DOIUrl":"https://doi.org/10.1111/aji.70148","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Human papillomavirus (HPV) is considered the necessary cause of cervical cancer. Studies showed that disruption of the inflammatory milieu in the cervicovaginal mucosa can promote the persistence of HPV, which can result in cervical carcinogenesis. This study determined sociodemographic factors and vaginal inflammatory cytokines associated with HPV infection in Manila, Philippines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Cervicovaginal swab samples from 110 sexually active women, ages 21 and above, from Manila, diagnosed using real-time PCR, were selected for comparative expression analysis using sandwich-type ELISA of the cytokines IL-6, IL-8, IL-1b, IL-10, and TNF-α. Independent <i>t</i>-test, Wilcoxon Rank Sum, and Chi-square test were employed. Multivariable logistic regression was conducted to determine factors associated with HPV infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sociodemographic and behavioral factors analyzed in this study did not show a significant association with HPV infection. IL-8 was significantly lower (<i>p</i> < 0.0001) while IL-10 was significantly higher (<i>p</i> < 0.001) in the HPV-positive group compared to the HPV-negative samples. Multivariable logistic regression showed that higher IL-1b (OR: 1.007; 95% CI: 1.003–1.012) and lower IL-8 levels (OR: 0.979; 95% CI: 0.970–0.989) were associated with increased odds of HPV infection. IL-8 promotes neutrophil recruitment and viral clearance, IL-1β drives inflammation but may foster persistence via IL-17 induction, and IL-10 suppresses antiviral immunity, enabling HPV evasion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study showed that lower IL-8 and higher IL-1β levels were independent predictors of HPV infection. These changes in the microenvironment may control immune cell infiltration and help establish HPV infection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935179","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":"Commentary on “Initial and Longitudinal Trajectories in Hemoglobin Levels Predict the Prognosis of Patients With Premature Rupture of Membranes”","authors":"Tinghua Zhang","doi":"10.1111/aji.70157","DOIUrl":"https://doi.org/10.1111/aji.70157","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935182","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}
Melania Maria Ramos Amorim, Anna Catharina Carneiro da Cunha, Giordana Campos Braga, Lucas Félix Marinho Neves, Marina Amorim Albuquerque, Alexandre Delgado, Edson Borges de Souza, Leila Katz
{"title":"American Society of Reproduction Immunology Guideline on Recurrent Pregnancy Loss: Between Evidence-Based Practice and Excessive Medicalization","authors":"Melania Maria Ramos Amorim, Anna Catharina Carneiro da Cunha, Giordana Campos Braga, Lucas Félix Marinho Neves, Marina Amorim Albuquerque, Alexandre Delgado, Edson Borges de Souza, Leila Katz","doi":"10.1111/aji.70152","DOIUrl":"https://doi.org/10.1111/aji.70152","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935247","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}