American Journal of Reproductive Immunology最新文献

{"title":"Recurrent Second-Trimester Euploid Pregnancy Loss Associated With Maternal–Paternal HLA Compatibility: Review Based on a Case Report of Immune-Mediated Failure","authors":"Sonia Gayete-Lafuente,&nbsp;Lara Guijarro-Baude,&nbsp;Elizabeth Choong,&nbsp;David Barad,&nbsp;Norbert Gleicher","doi":"10.1111/aji.70217","DOIUrl":"10.1111/aji.70217","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Recurrent pregnancy loss (RPL) is often unexplained, and emerging evidence supports a potential alloimmune contribution in a subset of patients. Excessive maternal–paternal HLA compatibility has been proposed as a mechanism impairing maternal–fetal immune tolerance. This review, based on a representative clinical case, examines the role of HLA sharing in recurrent euploid pregnancy loss.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>A narrative review of current literature on alloimmune mechanisms in RPL, including classical and non-classical HLA pathways and KIR-HLA interactions, was conducted. A clinical case involving recurrent second-trimester euploid losses despite multimodal immunotherapy was used to contextualize these mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The patient experienced multiple losses of chromosomally normal fetuses despite treatment with intravenous immunoglobulin, corticosteroids, hydroxychloroquine, progesterone, aspirin, and low-molecular-weight heparin. HLA typing demonstrated allele sharing across four of five loci, suggesting markedly reduced immunogenetic diversity at the maternal–fetal interface. This pattern aligned with proposed mechanisms of impaired trophoblast-immune signaling and inadequate tolerance induction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Excessive maternal–paternal HLA compatibility may contribute to recurrent euploid pregnancy loss through disruption of maternal–fetal immune tolerance. This case-based review underscores the need for individualized immunologic assessment and further research into targeted therapies for alloimmune-mediated reproductive failure.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200061","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":"Hofbauer Cells in Pregnancies Complicated by Gestational Diabetes Mellitus and Pathological Fetal Growth","authors":"Georgia Fakonti,&nbsp;Georgia Mappa,&nbsp;Nicolas Orsi,&nbsp;Eleanor M. Scott,&nbsp;Beth Holder,&nbsp;Karen Forbes","doi":"10.1111/aji.70216","DOIUrl":"10.1111/aji.70216","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Gestational diabetes mellitus (GDM) increases the risk of large-for-gestational-age (LGA) birth and long-term cardiometabolic complications in offspring, particularly in males. These outcomes are associated with altered placental vascularisation, but the underlying mechanisms remain poorly defined. Hofbauer cells (HBCs) are fetal-origin macrophages located in the villous stroma with established roles in immune regulation and vascularisation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>This study investigated whether HBC abundance and phenotype are associated with fetal growth, fetal sex, and placental vascularisation in term placentae from non-GDM and GDM pregnancies. Pan-macrophage (CD14, CD68), HBC-enriched (FOLR2, VSIG4), M1 (CD86), and M2 (CD163, MRC1) markers were assessed by RT-qPCR and quantitative immunohistochemistry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In both non-GDM and GDM placentae, all markers, except CD86 were detected, supporting an M2-like HBC phenotype. In GDM placentae, the number of pan-macrophage (CD68), HBC-enriched (FOLR2), and M2-associated (CD163, MRC1) cells were reduced in terminal villi compared with non-GDM controls (<i>p</i> &lt; 0.05; <i>n</i> = 13 non-GDM; <i>n</i> = 12 GDM), indicating reduced HBC abundance without phenotypic switching. Reduced expression of HBC-enriched (FOLR2, VSIG4) and M2-associated (CD163) transcripts supported these findings (<i>p</i> &lt; 0.05; <i>n</i> = 18 non-GDM; <i>n</i> = 19 GDM). No further differences were observed following stratification by fetal growth or sex. HBC-related gene expression correlated positively with the endothelial marker PECAM1/CD31, in both non-GDM and GDM placentae (<i>r</i> ≥ 0.5, <i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>HBCs abundance is reduced in GDM placentae independently of fetal growth or sex, whilst HBC phenotype is preserved. Reduced HBC abundance may contribute to placental vascular alterations that are characteristic of GDM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12906864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200003","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}

{"title":"SARS-CoV-2 Chronic Intervillositis: Variations of Maternal Antiviral Response","authors":"Daria Kozlova,&nbsp;Ori Mayer,&nbsp;Noam Shomron,&nbsp;Yosef Azan,&nbsp;Rani Shlayem,&nbsp;Yevgeni Yegorov,&nbsp;Nir Rainy,&nbsp;Avi Natan,&nbsp;Ana Foigelman Tobar","doi":"10.1111/aji.70215","DOIUrl":"10.1111/aji.70215","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Placental compromise is a determining factor in the outcome of pregnancies complicated by maternal SARS-CoV-2 infection. Chronic histiocytic intervillositis (CHI) is the initial response to SARS-CoV-2 infection, but the underlying mechanisms are poorly understood. The aim of this study was to assess the extent and composition of the placental inflammatory response and to explore the relationship between the severity of inflammation and viral levels in the placenta.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods of study</h3>\u0000 \u0000 <p>Placentas from 43 women who tested positive for SARS-CoV-2 infection at the time of delivery at a single tertiary medical center (8/2020 to 10/2022) were evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR), histopathological, ultrastructural, and in situ hybridization studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There was a significant association between viral load and severity of CHI with notable involvement of CD20-positive B lymphocytes (100% in patients with diffuse CHI vs 0% in the patients with no inflammation). Both PCR-positive and PCR-negative placentas exhibited varying degrees of inflammation. Electron microscopy confirmed viral particles in PCR- and CHI-negative samples, Additionally, mean gestational age at delivery was significantly lower in the PCR-positive patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings highlight the complex interplay between maternal SARS-CoV-2 infection and placental inflammation. The inflammatory response may extend beyond the presence of the virus per se, and viral load differences linked to individual immune response variability may influence the development of inflammation. Further research is needed to elucidate the mechanisms by which SARS-CoV-2 impacts maternal and neonatal health outcomes and provide insight into the implications of viral infections during pregnancy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12887547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146148804","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}

{"title":"Enhanced CD56 Expression and Increased Number of CD56+bright Cells in the Peripheral Blood of Untreated Endometriosis Patients","authors":"Emma Björk,&nbsp;Pernilla Israelsson,&nbsp;Olga Nagaeva,&nbsp;Lucia Mincheva-Nilsson,&nbsp;Ulrika Ottander","doi":"10.1111/aji.70214","DOIUrl":"10.1111/aji.70214","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>NK-cell dysfunction in endometriosis is suggested to contribute to the survival of ectopic endometrial tissue. However, the underlying causes of this impairment remain unclear. NK cells are divided into: CD56^+bright, which produce high amounts of cytokines but have low or no cytotoxic ability, and CD56^+dim, which are mainly cytotoxic. CD56^+bright NK cells, constitutively present in human endometrium (eNK cells), represent only 0–2% of NK cells in PBMC, where CD56^+dim cells dominate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>NK-cell subpopulations and NKG2D receptor expression in PBMC were analyzed by flow cytometry in two cohorts of untreated and treated endometriosis patients and healthy age-matched controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Elevated numbers of CD56^+bright cells were observed in 8 of 21 untreated endometriosis patients compared to controls. These numbers were normalized following surgery and hormonal treatment. The NKG2D receptor expression was reduced in untreated patients compared to controls and treated patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The significantly increased proportion of peripheral CD56^+brightNK/eNK cells may result from migration of these cells from ectopic endometrial tissue. The downregulation of NKG2D receptor expression in PBMCs may be mediated by immunosuppressive endometriotic exosomes, as previously reported by us. Taken together, our results suggest that: (1) the impaired NK cell cytotoxicity in untreated endometriosis patients may be due both to an influx of CD56^+bright/eNK cells and exosome-induced NKG2D receptor downregulation; and (2) elevated numbers of peripheral CD56^+bright NK cells could be considered as a potential diagnostic marker for endometriosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12873557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117637","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}

{"title":"Hydroxychloroquine Based Immunomodulatory Therapy Improves Pregnancy Outcomes in Women with Recurrent Implantation Failure Undergoing in Vitro Fertilization and Embryo Transfer","authors":"Ziyi Song,&nbsp;Fang Fang,&nbsp;Yunxia Gong,&nbsp;Yuke Hou,&nbsp;Wenqiong Wang,&nbsp;Chun Li,&nbsp;Xuewu Zhang,&nbsp;Qun Lu","doi":"10.1111/aji.70212","DOIUrl":"10.1111/aji.70212","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Recurrent implantation failure (RIF) remains a significant challenge in reproductive medicine, with immune dysfunction being a key contributing factor to implantation failure. However, data on the effectiveness of immunomodulatory therapy in RIF patients remain limited. This study aimed to assess the impact of immunomodulatory therapy on pregnancy outcomes in women with RIF undergoing in Vitro fertilization-embryo transfer (IVF-ET).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>This retrospective cohort study included women with RIF between 2016 and 2019. Patients in the treatment group received hydroxychloroquine (HCQ)-based immunomodulatory therapy after immunological evaluation, while those in the control group did not receive immunomodulatory treatment. Generalized estimating equations assessed the association between HCQ-based immunomodulatory therapy and pregnancy outcomes. Additionally, patients were stratified based on autoimmune antibody status, and subgroup analyses were conducted to further evaluate treatment effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 320 patients were included in the study, with 74 receiving HCQ-based immunomodulatory therapy (treatment group) and 246 undergoing IVF-ET alone (control group). The treatment group showed higher biochemical pregnancy (49.5% vs. 31.7%, <i>p</i> &lt; 0.001), clinical pregnancy (43.8% vs. 24.3%, <i>p</i> &lt; 0.001), embryo implantation (30.7% vs. 17.3%, p &lt; 0.001), and live birth rates (33.3% vs. 12.6%, p &lt; 0.001). Multivariate regression identified HCQ-based immunomodulatory therapy as an independent predictor of biochemical pregnancy (OR = 2.049, 95% CI: 1.440-2.915, <i>P</i>&lt;0.001), clinical pregnancy (OR = 2.424, 95% CI: 1.613-3.644, <i>P</i>&lt;0.001), and live birth (OR = 3.555, 95% CI: 2.235-5.652, <i>P</i>&lt;0.001). Stratified analysis confirmed its benefit in both autoimmune antibody positive and negative patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Real-world evidence revealed the potential role of HCQ-based immunomodulatory therapy in improving pregnancy outcomes in IVF-ET in patients with RIF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146091708","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":"Decidual CD4 Effector Memory and Resident Memory T Cells Respond to Cord Blood Allo-Antigens","authors":"Zachary T. Koenig,&nbsp;Shruti Eswar,&nbsp;Sayaka Tsuda,&nbsp;Nathan Schuldt,&nbsp;Claire A. Chougnet,&nbsp;Braxton Forde,&nbsp;Sandra Andorf,&nbsp;Tamara Tilburgs","doi":"10.1111/aji.70213","DOIUrl":"10.1111/aji.70213","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Maternal CD4 T cells are critical coordinators of maternal–fetal immune tolerance and immunity during pregnancy. Decidual regulatory T cells (T_REG) have been shown to provide essential immune suppressive functions to control allogeneic responses and inflammation. Activated CD4 memory T cells form the largest fraction of decidual T cells, yet their diversity, specificity, and functions remain largely undefined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Using high-dimensional flow cytometry (HDFC), computational and functional analysis to characterize decidual CD4 memory T-cell types and their functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two types of decidual CD4 T cells, the effector memory cells (T_EM), and CD69+ PD1+ resident memory cells (T_RM) with a strong capacity to respond to cord blood allo-antigens were identified. Important differences were found in their phenotypic, cytotoxic, and cytokine profiles that were dependent on fetal sex, mode of delivery, and human cytomegalovirus (HCMV) serology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Thus, decidual CD4 T_EM and T_RM have unique immune effector functions and the ability to recognize and respond to fetal cord blood. This suggests that decidual CD4 T_EM and T_RM cells can recognize fetal allo-antigens and, when not adequately controlled, may contribute to placental inflammation. Further definition of decidual T_EM and CD69+ PD1+ T_RM immune effector functions and specificity has clinical significance to define essential drivers of healthy pregnancy and pregnancy complications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12859743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146091679","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}

{"title":"Gut Microbiota Changes After Hormonal or Surgical Treatment for Endometriosis","authors":"Yosuke Ono,&nbsp;Osamu Yoshino,&nbsp;Takeshi Sasayama,&nbsp;Masami Ito,&nbsp;Tatsuya Yoshihara,&nbsp;Kota Tanaka,&nbsp;Akiko Nakagomi,&nbsp;Satoko Sasatsu,&nbsp;Maki Ogi,&nbsp;Hikaru Tagaya,&nbsp;Tomohiko Fukuda,&nbsp;Takeshi Nagamatsu,&nbsp;Takuji Yamada","doi":"10.1111/aji.70211","DOIUrl":"10.1111/aji.70211","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Although studies have suggested a link between gut microbiota and endometriosis pathophysiology, the effects of treatment for endometriosis remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this prospective observational study, 27 patients with stage III/IV endometriosis and 17 healthy controls provided a total of 56 fecal samples. In endometriosis patients, gut microbiota profiles were analyzed before and after hormonal therapy or surgery to assess treatment-related changes. 16S rRNA gene sequencing was used for microbiota analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No differences in α- or β-diversity were observed between the endometriosis and control groups, although patients with endometriosis had high levels of <i>Acidaminococcus</i>, <i>Lachnoclostridium</i>, and <i>Paraprevotella</i> and low levels of <i>Odoribacter</i> (all <i>p</i> &lt; 0.05). Among the eight patients who received hormonal therapy, no significant changes in α- and β-diversity were observed between the pre- and post-treatment samples. A comparison of samples from the same individuals showed an increase in <i>Blautia</i>, which is associated with mental health stability, and a decrease in <i>Sutterella</i>, which is involved in regulating the intestinal barrier. In an exploratory analysis of patients without recurrence after surgery (<i>n</i> = 4), α-diversity significantly increased (<i>p</i> = 0.035), with stable β-diversity. Postsurgical increases were observed in 10 genera, including six inflammation-related taxa; five (<i>Flavonifractor</i>, <i>[Eubacterium]_brachy_group</i>, <i>Hungatella</i>, <i>Incertae_Sedis</i>, and <i>Fournierella</i>) are associated with anti-inflammatory effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Hormonal therapy for endometriosis may help not only to control lesions but also to support mental health. Surgical treatment may alter the composition of inflammation-associated gut bacteria; however, these exploratory results from a small cohort should be interpreted with caution. Further studies with larger sample sizes are warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028099","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":"Mouse Trophoblast Stem Cells Are Deficient in TNFα-Activated NFκB Signaling Pathway and Inflammatory Response","authors":"Yeseul Bae,&nbsp;Marwah Walid Ali Alzara,&nbsp;Yan-Lin Guo","doi":"10.1111/aji.70208","DOIUrl":"10.1111/aji.70208","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>We recently reported that trophoblast stem cells (TSCs) and TSC-differentiated trophoblasts (TSC-TBs) do not respond to TNFα. This immunological property enables these cells to avoid the cytotoxic effects induced by the combination of TNFα and IFNγ. The goal of this study is to elucidate the molecular basis for the unresponsiveness of TSCs and TSC-TBs to TNFα and assess the functionality of TNFα signaling pathways in these cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We compared the responses of TSCs and TSC-TBs to TNFα with those of mouse embryonic fibroblasts (MEFs). Genome-wide transcriptomic profiling was performed using RNA-seq data, including the TNFα signaling pathway, TNFα-induced expression of NFκB target genes, and the transcriptional changes and functional pathway enrichment associated with TSC differentiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The data provide a comprehensive view of TNFα-induced NFκB activation and the subsequent induction of NFκB target genes with diverse functions. In MEFs, TNFα upregulates or downregulates the transcription of numerous NFκB target genes, but it has little to no effect on gene expression in TSCs and TSC-TBs. Nevertheless, many NFκB target genes essential for shared or cell type-specific functions are expressed in TSCs and TSC-TBs and are regulated in a cell type-specific manner.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results provide the molecular basis for the lack of TNFα-induced inflammatory responses in TSCs and TSC-TBs. They also suggest that TSCs and TSC-TBs have evolved mechanisms to avoid the cytotoxic effects associated with TNFα-induced inflammation response, while still permitting the expression of other NFκB target genes essential for their cellular functions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008473","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":"Role of Myeloid-Derived Suppressor Cells as a Potential Biomarker in Implanation Failure: A Systematic Review","authors":"Shubhangi Jha,&nbsp;Suresh Singh Yadav,&nbsp;Rohina Aggarwal,&nbsp;Rohini R. Nair","doi":"10.1111/aji.70203","DOIUrl":"10.1111/aji.70203","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Pregnancy requires maternal immune tolerance of the semi-allogeneic fetus without compromising host defense. Myeloid-derived suppressor cells (MDSCs) have emerged as key regulators of maternal fetal tolerance, but their role in early miscarriage (EM), recurrent pregnancy loss (RPL), and recurrent implantation failure (RIF) remains incompletely defined.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To systematically evaluate the role of MDSCs in EM, RPL, and RIF and assess their potential as biomarkers and therapeutic targets in implantation failure and pregnancy loss.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methodology&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A systematic review in accordance with PRISMA guidelines. Searches were conducted in Google Scholar up to April 13, 2025, using the terms “Myeloid Derived Suppressor Cells,” “in vitro fertilization,” “early miscarriage,” “pregnancy loss,” and “implantation failure.” Studies were eligible if they quantified MDSCs in peripheral blood or endometrial samples of women with EM, RPL, or RIF and animal-only studies. Reviews, abstracts, and inaccessible full texts were excluded.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Of 70 records identified, 11 met inclusion criteria (seven human, five murine, one has included human samples and murine models). In human studies, reduced granulocytic MDSCs (G-MDSCs) were strongly associated with EM and RPL, correlating with low estradiol/progesterone, impaired STAT3 signaling, and a Th1-dominant cytokine milieu. Findings in RIF were heterogeneous: some reported decreased polymorphonuclear MDSCs with functional impairment, while others observed elevated monocytic MDSCs (M-MDSCs) with diminished suppressive capacity, suggesting dysfunctional or compensatory expansion. Placental enrichment of G-MDSCs demonstrated their tolerogenic role in situ, promoting Treg induction and macrophage polarization. Murine models confirmed it as the cause since MDSC depletion abolished pregnancy, while progesterone-STAT3-ROS signaling supported their expansion and suppressive function. Adoptive MDSC transfer partially rescued fetal resorption in abortion-prone models.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;MDSCs are central to maternal fetal tolerance, and their dysregulation contributes to EM, RPL, and RIF. Human and animal data support their potential as predictive biomarkers and therapeutic targets in implantation failure. Standardization of MDSC phenotyping and mechanistic studies of subset-specific functions are warranted to advance clinical translation.&lt;/p&gt;\u0000 &lt;/","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145996984","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":"Testosterone-Induced Pyroptotic Death of Ovarian Granulosa Cells in PCOS Might Involve Both GSDMD and GSDME, the Latter Possibly Enabling a Crosstalk Between Apoptosis and Pyroptosis","authors":"Caglar Berkel","doi":"10.1111/aji.70207","DOIUrl":"10.1111/aji.70207","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997077","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}