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Aberrant Expression of Gonadotropin-Releasing Hormone Receptor in Human Mast Cells Enhances the Recruitments of Trophoblasts and NK Cells 促性腺激素释放激素受体在人肥大细胞中的异常表达促进滋养细胞和NK细胞的募集。
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-18 DOI: 10.1111/aji.70168
Takashi Matsuzaki, Hiroaki Hamaguchi, Ken R. Ito, Ryota Nakagawa, Hiroya Nakamura, Hiroaki Ito, Chiyuki Ueshima, Akihiko Yoshizawa, Hironori Haga, Tatsuki R. Kataoka

Problem

Gonadotropin-releasing hormone (GnRH), primarily known for its hypothalamic role in regulating gonadotropin secretion, is also expressed in extra-hypothalamic tissues, including trophoblasts at implantation sites. We investigated the association between trophoblasts and mast cells, demonstrating their role in producing leukemia inhibitory factor (LIF) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesized an additional interaction between trophoblasts and mast cells mediated by GnRH.

Method of Study

Immunohistochemical analysis was conducted to investigate GnRH receptor (GnRHR) expressing mast cell in endometrial and tubal tissues from both pregnant and non-pregnant conditions (2005–2018). We established a human mast cell line LAD2 with forced expression of GnRHR expression (GnRHR-expressing LAD2) via lentiviral transfection method. The cells were stimulated with or without leuprorelin (1 µM) and transcriptomic analysis and cell migration assays were conducted.

Results

GnRHR is expressed in decidual mast cells during uterine pregnancy and in mast cells adjacent to or embedded in trophoblasts of tubal pregnancy. Notably, GnRHR expression was also observed in endometrial mast cells in non-pregnancy conditions. The levels of transcripts encoding LIF, MMP-9, and a natural killer (NK) cell attractant C-X-C motif chemokine ligand 16 (CXCL16) were significantly upregulated in GnRHR-expressing LAD2 than in control cells. In addition, culture supernatants from GnRHR-expressing LAD2 cells enhanced the migration of the trophoblast cell line HTR-8/SVneo and the NK cell line NK-92 MI.

Conclusions

These findings suggest that GnRHR expression in mast cells promotes their supportive role in pregnancy establishment by increasing the LIF, MMP-9, and CXCL16 productions, recruiting trophoblasts and NK cells.

问题:促性腺激素释放激素(GnRH)主要在下丘脑调节促性腺激素分泌,也在下丘脑外组织表达,包括着床部位的滋养细胞。我们研究了滋养细胞和肥大细胞之间的关系,证明了它们在产生白血病抑制因子(LIF)和基质金属蛋白酶-9 (MMP-9)中的作用。因此,我们假设滋养层细胞和肥大细胞之间有GnRH介导的额外相互作用。研究方法:采用免疫组化方法研究2005-2018年妊娠和非妊娠患者子宫内膜和输卵管组织肥大细胞中GnRH受体(GnRHR)表达情况。我们通过慢病毒转染法建立了强制表达GnRHR的人肥大细胞系LAD2(表达GnRHR的LAD2)。用leuprorelin(1µM)或不加leuprorelin刺激细胞,进行转录组学分析和细胞迁移实验。结果:GnRHR在子宫妊娠期间的肥大细胞中表达,在输卵管妊娠滋养细胞附近或包埋的肥大细胞中表达。值得注意的是,在非妊娠条件下,子宫内膜肥大细胞中也观察到GnRHR的表达。在表达gnrhr的LAD2细胞中,编码LIF、MMP-9和自然杀伤(NK)细胞引诱剂C-X-C基序趋化因子配体16 (CXCL16)的转录本水平显著高于对照细胞。此外,表达GnRHR的LAD2细胞培养上清液增强了滋养细胞HTR-8/SVneo和NK细胞NK-92 mi的迁移。结论:这些发现表明,肥大细胞中表达GnRHR通过增加LIF、MMP-9和CXCL16的产生,募集滋养细胞和NK细胞,促进了它们在妊娠建立中的支持作用。
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引用次数: 0
Revealing the Complexity of Immunobiological Shifts From Non-Pregnant to Pregnant State 揭示从未怀孕到怀孕状态的免疫生物学转变的复杂性。
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-18 DOI: 10.1111/aji.70166
Chelsea A. DeBolt, Haocheng Yu, Valerie Riis, Liqhwa Ncube, Amir Horowitz, Michal A. Elovitz

Problem

Significant immunological shifts, systemically and at the maternal–fetal interface, are required for successful pregnancy. As immune perturbations are emerging as pivotal drivers of adverse maternal health, elucidating how normal pregnancy alters maternal systemic immunity is imperative.

Methods

From our prospectively enrolled cohort of Black women, peripheral blood samples were collected pre-pregnancy (V1) and in the second trimester (16–24 weeks, V2). Among those who became pregnant, 23 had available samples from both time points. RNA was extracted and subjected to bulk RNA sequencing, followed by differential gene expression analyses, immune cell-type deconvolution, and pathway enrichment analyses. Participants were stratified by pre-pregnancy obesity (body mass index ≥ 30 kg/m2) to examine its impact on pregnancy-induced immune changes.

Results

Pathway analyses revealed innate immune activation and increased neutrophil-driven inflammation during pregnancy. Significant increase in neutrophils and monocytes occurred during pregnancy, whereas naïve CD8+ T-cell and B-cell subsets were significantly decreased. Pre-pregnancy obesity amplified these changes, further increasing innate populations (gamma delta T cells, neutrophils) and decreasing adaptive populations (CD8 naïve T cells, B memory cells).

Conclusion

From individuals with uncomplicated pregnancies, we demonstrate dramatic immunological changes when transitioning from a non-pregnant to pregnant state. Intricate immune modulation, including changes in inflammatory mechanisms and immune cell dynamics were observed. Pre-pregnancy obesity enhances these inflammatory shifts, providing insights into potential mechanisms driving adverse pregnancy outcomes in obese women. Future studies investigating how these immunological shifts are required for optimal maternal health and/or may promote increased vulnerability to adverse pregnancy outcomes will create new opportunities to improve maternal outcomes.

问题:成功怀孕需要全身和母胎界面的显著免疫变化。由于免疫紊乱正在成为孕产妇健康不良的关键驱动因素,阐明正常妊娠如何改变孕产妇全身免疫是必要的。方法:从前瞻性纳入的黑人妇女队列中,收集妊娠前(V1)和妊娠中期(16-24周,V2)的外周血样本。在怀孕的人中,有23人有两个时间点的可用样本。提取RNA并进行大量RNA测序,随后进行差异基因表达分析、免疫细胞型反褶积和途径富集分析。根据孕前肥胖(体重指数≥30 kg/m2)对参与者进行分层,以检查其对妊娠引起的免疫变化的影响。结果:途径分析显示妊娠期先天免疫激活和中性粒细胞驱动的炎症增加。怀孕期间中性粒细胞和单核细胞显著增加,而naïve CD8+ t细胞和b细胞亚群显著减少。孕前肥胖放大了这些变化,进一步增加了先天种群(γ δ T细胞、中性粒细胞),减少了适应性种群(CD8 naïve T细胞、B记忆细胞)。结论:从个体无并发症妊娠,我们证明了戏剧性的免疫变化,从非怀孕过渡到怀孕状态。观察到复杂的免疫调节,包括炎症机制和免疫细胞动力学的变化。孕前肥胖增强了这些炎症转变,为肥胖妇女不良妊娠结局的潜在机制提供了见解。未来研究如何需要这些免疫变化来实现最佳的孕产妇健康和/或可能增加对不良妊娠结果的脆弱性,将为改善孕产妇结局创造新的机会。
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引用次数: 0
Comment on “Deciphering the Molecular Crosstalk of Endoplasmic Reticulum Stress and Immune Infiltration in Endometriosis” 《解读子宫内膜异位症内质网应激与免疫浸润的分子串扰》述评
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-15 DOI: 10.1111/aji.70158
Saraswati Sah, Renu Sah
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引用次数: 0
Endothelial Activation and Stress Index as a Novel Prognostic Marker in Intrahepatic Cholestasis of Pregnancy: A Case–Control Study 内皮细胞激活和应激指数作为妊娠肝内胆汁淤积的一种新的预后指标:一项病例对照研究
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-15 DOI: 10.1111/aji.70167
Dilara Duygulu Bulan, Ruken Dayanan, Merve Ayas Özkan, Zeynep Şeyhanlı, Gülşan Karabay, Ali Turhan Çağlar

Objective: This study aims to evaluate the clinical applicability and prognostic value of the endothelial activation and stress index (EASIX) in patients with intrahepatic cholestasis of pregnancy (ICP). By investigating the potential of the EASIX score to predict perinatal complications and the clinical course of ICP, we seek to contribute to the improved management and prognosis of ICP patients.

Methods: This retrospective cohort study aimed to investigate the prognostic value of the EASIX in patients diagnosed with ICP at Ankara Etlik City Hospital between January 2023 and January 2025. A total of 121 ICP patients and 133 control patients were included. The EASIX score was calculated using lactate dehydrogenase, creatinine and thrombocyte levels. The relationship between EASIX and perinatal complications, including preterm birth and neonatal distress, was assessed.

Results: The EASIX score was significantly higher in the ICP group compared to controls (p < 0.001), with severe ICP showing the highest EASIX scores (p = 0.019). Cut-off analysis indicated that an EASIX score > 0.64 had a sensitivity of 75% and specificity of 64% for severity prediction (AUC = 0.767, p < 0.001), while a score > 0.69 had a sensitivity of 62% and specificity of 61% for predicting composite adverse perinatal outcomes (AUC = 0.711, p < 0.001).

Conclusion: This study demonstrates that the EASIX score may serve as an important prognostic tool in predicting disease severity and neonatal outcomes in ICP. Given the limited availability of bile acid measurements in some clinics, the EASIX score provides a practical and accessible alternative for clinical use. This study evaluates the prognostic value of the endothelial activation and stress index (EASIX) in intrahepatic cholestasis of pregnancy, highlighting its potential to predict disease severity and neonatal outcomes, offering a practical tool for clinical use.

目的:探讨内皮活化与应激指数(EASIX)在妊娠肝内胆汁淤积症(ICP)患者中的临床适用性及预后价值。通过研究EASIX评分预测围产儿并发症和ICP临床病程的潜力,我们试图为改善ICP患者的管理和预后做出贡献。方法:本回顾性队列研究旨在探讨EASIX对2023年1月至2025年1月在安卡拉埃特利克市医院诊断为ICP患者的预后价值。共纳入121例ICP患者和133例对照患者。EASIX评分采用乳酸脱氢酶、肌酐和血小板水平计算。评估EASIX与围产期并发症(包括早产和新生儿窘迫)之间的关系。结果:ICP组的EASIX评分明显高于对照组(p < 0.001),其中重度ICP的EASIX评分最高(p = 0.019)。截止分析显示,EASIX评分为>; 0.64时预测严重程度的敏感性为75%,特异性为64% (AUC = 0.767, p < 0.001),而评分为>; 0.69时预测围产期综合不良结局的敏感性为62%,特异性为61% (AUC = 0.711, p < 0.001)。结论:本研究表明EASIX评分可作为预测ICP疾病严重程度和新生儿结局的重要预后工具。鉴于胆汁酸测量在一些诊所的可用性有限,EASIX评分为临床使用提供了一个实用和可访问的替代方案。本研究评估了内皮细胞激活和应激指数(EASIX)在妊娠肝内胆汁淤积中的预后价值,强调了其预测疾病严重程度和新生儿结局的潜力,为临床应用提供了实用工具。
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引用次数: 0
Re: “Elevated Neutrophil, Lymphocyte, and Platelet Counts as Early Biomarkers of Preeclampsia Risk: A Retrospective Cohort Study” 嗜中性粒细胞、淋巴细胞和血小板计数升高作为子痫前期风险的早期生物标志物:一项回顾性队列研究
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-15 DOI: 10.1111/aji.70160
Tirayut Veerasathian, Schawanya K. Rattanapitoon, Chadaporn N. Gordon, Nathkapach K. Rattanapitoon
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引用次数: 0
Decidual Cells Induce Release of Free and Exosome-Bound Interferon Epsilon From Vaginal Epithelial Cells 蜕细胞诱导游离和外泌体结合干扰素Epsilon从阴道上皮细胞释放
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-12 DOI: 10.1111/aji.70129
Emmanuel Amabebe, Lauren S. Richardson, Awanit Kumar, Ramkumar Menon, Brandie D. Taylor

Problem

We tested the hypothesis that oxidative stress (OS)-induced inflammatory response in decidual cells (DECs) may transfer and/or trigger the release of interferon epsilon (IFNε)-positive extracellular vesicles (EVs) from vaginal epithelial cells (VECs) to minimize vaginal disturbances.

Method of Study

VECs were treated for 48 h under the following conditions: (1) standard VEC media, (2) OS-inducing cigarette smoke extract (CSE); and supernatant from (3) normal/untreated DECs, and (4) CSE-treated DECs. The concentration of cytoplasmic, secreted, and VEC-derived EV bound IFNε (n = 3 each) was measured by enzyme-linked immunosorbent assay (ELISA). EVs were isolated from culture media by cushioned-density gradient ultracentrifugation and characterized by immunoblotting and nanoparticle tracking analysis.

Results

Induction of OS in VECs with CSE increased intracellular IFNε in VECs (p = 0.0007) but not free or EV-bound IFNε compared to control VECs. Exposure to conditioned media from untreated and CSE-treated DECs induced increased intracellular (p = 0.004, p = 0.049) and free IFNε (p = 0.04, p = 0.03) from VECs. VEC-derived EVs (126 ± 11.8 nm) expressed exosome markers, and did not change in size regardless of the treatment but decreased in number due to exposure to untreated (p = 0.004) and CSE-treated DECs (p = 0.025) conditioned media. Furthermore, VEC exosomal IFNε increased by 2.6-fold (p = 0.0001, untreated DECs) and ∼4-fold (p = 0.041, CSE-treated DECs) compared to controls.

Conclusions

Mucosal immune defense mediated by IFNε may be an innate response by VECs under OS. This was further evidenced by an overall increase in IFNε due to both physiologic and pathologic impact of decidua on VECs. IFNε may indicate a stress response by VECs or paracrine crosstalk between gestational tissues.

我们验证了一种假设,即氧化应激(OS)诱导的蜕细胞(DECs)炎症反应可能转移和/或触发阴道上皮细胞(VECs)中干扰素ε (IFNε)阳性的细胞外囊泡(EVs)的释放,以减少阴道紊乱。在以下条件下处理VEC 48 h:(1)标准VEC培养基;(2)诱导os的香烟烟雾提取物(CSE);(3)正常/未经处理的DECs和(4)cse处理的DECs的上清液。采用酶联免疫吸附试验(ELISA)测定细胞质、分泌和vec来源的EV结合IFNε (n = 3)的浓度。采用缓冲密度梯度超离心技术从培养基中分离出ev,并采用免疫印迹和纳米颗粒跟踪分析对其进行鉴定。结果与对照VECs相比,CSE诱导的VECs OS增加了VECs细胞内IFNε (p = 0.0007),但没有增加游离IFNε或与ev结合的IFNε。未处理和cse处理的DECs暴露于条件培养基中,细胞内IFNε (p = 0.004, p = 0.049)和游离IFNε (p = 0.04, p = 0.03)增加。vec衍生的EVs(126±11.8 nm)表达外泌体标记物,无论处理如何,其大小都没有变化,但由于暴露于未处理(p = 0.004)和cse处理的DECs (p = 0.025)条件培养基,其数量减少。此外,与对照组相比,VEC外泌体IFNε增加了2.6倍(p = 0.0001,未治疗的DECs)和约4倍(p = 0.041, cse治疗的DECs)。结论IFNε介导的粘膜免疫防御可能是内皮细胞在OS下的先天反应。由于蜕膜对VECs的生理和病理影响,IFNε的总体增加进一步证明了这一点。IFNε可能表明VECs的应激反应或妊娠组织间的旁分泌串扰。
{"title":"Decidual Cells Induce Release of Free and Exosome-Bound Interferon Epsilon From Vaginal Epithelial Cells","authors":"Emmanuel Amabebe,&nbsp;Lauren S. Richardson,&nbsp;Awanit Kumar,&nbsp;Ramkumar Menon,&nbsp;Brandie D. Taylor","doi":"10.1111/aji.70129","DOIUrl":"https://doi.org/10.1111/aji.70129","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>We tested the hypothesis that oxidative stress (OS)-induced inflammatory response in decidual cells (DECs) may transfer and/or trigger the release of interferon epsilon (IFNε)-positive extracellular vesicles (EVs) from vaginal epithelial cells (VECs) to minimize vaginal disturbances.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>VECs were treated for 48 h under the following conditions: (1) standard VEC media, (2) OS-inducing cigarette smoke extract (CSE); and supernatant from (3) normal/untreated DECs, and (4) CSE-treated DECs. The concentration of cytoplasmic, secreted, and VEC-derived EV bound IFNε (<i>n</i> = 3 each) was measured by enzyme-linked immunosorbent assay (ELISA). EVs were isolated from culture media by cushioned-density gradient ultracentrifugation and characterized by immunoblotting and nanoparticle tracking analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Induction of OS in VECs with CSE increased intracellular IFNε in VECs (<i>p</i> = 0.0007) but not free or EV-bound IFNε compared to control VECs. Exposure to conditioned media from untreated and CSE-treated DECs induced increased intracellular (<i>p</i> = 0.004, <i>p</i> = 0.049) and free IFNε (<i>p</i> = 0.04, <i>p</i> = 0.03) from VECs. VEC-derived EVs (126 ± 11.8 nm) expressed exosome markers, and did not change in size regardless of the treatment but decreased in number due to exposure to untreated (<i>p</i> = 0.004) and CSE-treated DECs (<i>p</i> = 0.025) conditioned media. Furthermore, VEC exosomal IFNε increased by 2.6-fold (<i>p</i> = 0.0001, untreated DECs) and ∼4-fold (<i>p</i> = 0.041, CSE-treated DECs) compared to controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Mucosal immune defense mediated by IFNε may be an innate response by VECs under OS. This was further evidenced by an overall increase in IFNε due to both physiologic and pathologic impact of decidua on VECs. IFNε may indicate a stress response by VECs or paracrine crosstalk between gestational tissues.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification and Exploration of Novel B Cell Infiltration-Related Biomarkers in Endometriosis 子宫内膜异位症中新型B细胞浸润相关生物标志物的鉴定与探索
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-09 DOI: 10.1111/aji.70159
Chunyang Zhao, Shuwei Zhang, Baosu Zhang, Hang Tian, Guojun Yan, Hongbo Zhao

Objective

To explore B cell infiltration-related genes in endometriosis (EM) and investigate their potential as diagnostic biomarkers.

Methods

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.

Results

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.

Conclusion

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.

目的探讨子宫内膜异位症(endometriosis, EM) B细胞浸润相关基因,并探讨其作为诊断生物标志物的潜力。方法分析GSE51981数据库中77例子宫内膜异位症患者和34例对照患者的基因表达数据,检测差异表达基因(DEGs)。应用xCell算法估计64种免疫细胞和基质细胞类型的浸润水平,重点是B细胞和幼稚B细胞。加权基因共表达网络分析(WGCNA)鉴定了与B细胞浸润相关的基因模块。使用LASSO和SVM-RFE机器学习方法筛选潜在的生物标志物基因。然后,在独立的GSE7305数据集中验证枢纽基因,并使用Pearson相关分析评估枢纽基因与B细胞标记物之间的相关性。结果共筛选到4341个deg,其中包含349个基因的绿黄模块与EM病变中B细胞浸润特征相关,然后通过机器学习方法鉴定出12个B细胞浸润相关基因。基于外部GSE7305数据集,四个中心基因NR4A1、TNS1、ZNF521和CMPK2被认为是EM中B细胞浸润的潜在生物标志物,并且它们都显著上调。结论本研究鉴定并探索了4种潜在的EM诊断生物标志物,通过生物信息学分析确定了4种生物标志物的功能以及B细胞浸润在EM中的作用,为从免疫和分子水平研究子宫内膜异位症提供了新的思路。
{"title":"Identification and Exploration of Novel B Cell Infiltration-Related Biomarkers in Endometriosis","authors":"Chunyang Zhao,&nbsp;Shuwei Zhang,&nbsp;Baosu Zhang,&nbsp;Hang Tian,&nbsp;Guojun Yan,&nbsp;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}
引用次数: 0
Maternal-Fetal Interface Cell Dysfunction in Patients With Preeclampsia Revealed via Single-Cell RNA Sequencing 通过单细胞RNA测序揭示子痫前期患者的母胎界面细胞功能障碍
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-09 DOI: 10.1111/aji.70101
Songyuan Xiao, Yiling Ding, Ling Yu, Yali Deng, Yang Zhou, Mei Peng, Weisi Lai, Yanting Nie, Wen Zhang

Problem

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.

Method of Study

Patients included those diagnosed with PE (n = 3) and normal pregnancy (NP) (n = 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.

Results

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.

Conclusions

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.

问题先兆子痫(PE)是围产期产妇和胎儿死亡的主要原因。临床和病理研究表明,胎盘和蜕膜细胞功能障碍可能导致这种情况。然而,PE的发病机制仍然知之甚少。因此,本研究旨在利用单细胞测序技术研究剖宫产胎盘和蜕膜组织中细胞类型的异质性变化。研究方法患者包括诊断为PE (n = 3)和正常妊娠(n = 3)的患者。总共鉴定出9种细胞类型,包括绒毛细胞滋养细胞(VCT)、合胞滋养细胞(SCT)、胞外滋养细胞(EVT)、内皮细胞、中性粒细胞、Hofbauer细胞、T细胞、树突状细胞(DC)、巨噬细胞、成纤维细胞和B细胞,共32279个细胞(PE: 16.575; NP: 15 704)。分析VCT和T细胞亚群及假时间。体内和体外实验主要研究了EVT的侵袭能力。结果通过差异表达基因的基因集变异分析(GSVA)、细胞重聚和伪时间分析,PE患者的VCT表现出向SCT而非EVT分化的趋势。侵袭相关基因TMEM200A的表达降低了PE EVT细胞的侵袭能力。另外,T细胞分化为CD8+T细胞而非Treg细胞的免疫环境受损是与PE相关的主要变化。这些发现表明,了解T细胞在妊娠早期如何分化以及CD8+T细胞驱动的免疫环境如何影响VCT分化对于阐明PE的发病机制至关重要。
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引用次数: 0
Determination of Apoptotic Pathways in Ovarian Folicular Fluid of Infertile Patients With Endometrioma in Relation to Follicular Atresia 子宫内膜异位瘤不孕患者卵泡液细胞凋亡通路与卵泡闭锁的关系
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-09 DOI: 10.1111/aji.70164
Yağmur Soykan, Atiye Seda Yar Sağlam, Asiye Uğraş Dikmen, Mehmet Erdem, Ahmet Erdem

Problem

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.

Method of Study

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.

Results

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 (p < 0.05), while anti-apoptotic genes like BCL-2 and BCL2L1 were significantly lower (p < 0.05) as compared to controls. These results suggest a potential link between these gene expression alterations and infertility.

Conclusion

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.

问题子宫内膜异位症是一种慢性炎症性疾病,可导致盆腔疼痛和不孕。最近的研究表明,免疫、内分泌、生化和遗传异常,以及卵母细胞、胚胎和子宫内膜环境的不理想质量,显著影响与子宫内膜异位症相关的不孕。子宫内膜异位症的异位子宫内膜细胞具有避免细胞凋亡的能力。因此,细胞凋亡在子宫内膜异位症的发病中起着重要的作用。本研究旨在探讨卵泡液(FF)中凋亡相关基因(特别是Caspase 3 (CASP3)、Caspase 8 (CASP8)、Caspase 9 (CASP9)、BCL-2、BCL2L1、BAX、BAK、PERFORIN和GRANZYME B (GrB))信使RNA (mRNA)表达水平与不孕症的关系。研究方法分析了上述基因的mRNA表达水平,这些基因是在不育患者接受体外受精后,在控制卵巢过度刺激后的卵母细胞提取过程中获得的FF中表达的。结果我们发现子宫内膜瘤的存在与FF细胞凋亡相关基因mRNA表达水平的改变有关。其中,促凋亡基因的表达水平显著高于对照组(p < 0.05),而抗凋亡基因如BCL-2和BCL2L1的表达水平显著低于对照组(p < 0.05)。这些结果表明,这些基因表达改变与不孕症之间存在潜在联系。结论本初步研究为进一步了解细胞凋亡相关基因的mRNA表达水平提供了重要依据。这些发现可能揭示细胞凋亡途径中治疗子宫内膜异位瘤妇女不孕症的潜在治疗靶点。
{"title":"Determination of Apoptotic Pathways in Ovarian Folicular Fluid of Infertile Patients With Endometrioma in Relation to Follicular Atresia","authors":"Yağmur Soykan,&nbsp;Atiye Seda Yar Sağlam,&nbsp;Asiye Uğraş Dikmen,&nbsp;Mehmet Erdem,&nbsp;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> &lt; 0.05), while anti-apoptotic genes like BCL-2 and BCL2L1 were significantly lower (<i>p</i> &lt; 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}
引用次数: 0
Potential Involvement of NINJ1-Mediated Plasma Membrane Rupture in Lytic Death of Granulosa Cells in PCOS nin1介导的质膜破裂可能参与多囊卵巢综合征颗粒细胞的溶解性死亡
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-08 DOI: 10.1111/aji.70161
Caglar Berkel
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引用次数: 0
期刊
American Journal of Reproductive Immunology
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