American Journal of Reproductive Immunology最新文献

{"title":"MiR-29c-3p Impairs the Adhesion of Endometrial Epithelial Cells via COL4A1/β-catenin in Endometriosis","authors":"Chengyuan Li,&nbsp;Jian Li,&nbsp;Xin Li,&nbsp;Lan Geng,&nbsp;Qiuju Zhang,&nbsp;Zhenhui Hou,&nbsp;Xi Xia","doi":"10.1111/aji.70291","DOIUrl":"10.1111/aji.70291","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Defective endometrial receptivity is an indispensable cause of infertility in endometriosis, yet the post-transcriptional regulatory mechanisms underlying this impairment remain poorly understood. The goal of this research was to describe how miR-29c-3p and its target, COL4A1, regulate endometrial epithelial cell function and embryo adhesion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Endometrial epithelial cells were obtained from 14 women (including 7 with endometriosis and 7 controls) undergoing in vitro fertilization (IVF). Expression levels of miR-29c-3p and COL4A1 were quantified. Gain- and loss-of-function tests were employed in Ishikawa cells to assess cell adhesion capabilities and delineate downstream signaling pathways implicated in implantation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Women with endometriosis had considerably higher levels of miR-29c-3p expression in their endometrial epithelium. Mechanistically, increased expression of miR-29c-3p suppressed COL4A1, downregulated E-cadherin, and impaired JAr spheroid attachment. Notably, COL4A1 knockdown recapitulated these phenotypes by encouraging epithelial-mesenchymal transition (EMT), thereby compromising adhesive capacity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings identify the miR-29c-3p/COL4A1/<i>β</i>-catenin axis as a pivotal hub controlling endometrial epithelial adhesion. In patients with endometriosis, this axis could be a potential molecular candidate to enhance fertility outcomes and restore endometrial receptivity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70291","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148704981","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":"Maternal High Fat Diet and Acute Viral Mimic Exposure Impact Placental Inflammation, Lipid Peroxidation and Cellular Proliferation-to-Death Ratio Across Mouse Pregnancy","authors":"Thaina Ferraz,&nbsp;Lucas Cardoso,&nbsp;Sadra Mohammadkhani,&nbsp;Enrrico Bloise,&nbsp;Kristin L. Connor","doi":"10.1111/aji.70290","DOIUrl":"10.1111/aji.70290","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Maternal obesity and viral infection induce placental inflammation, but how their co-exposure influence fetoplacental development remains unclear. We hypothesised that maternal high fat (HF) diet and viral infection would independently induce placental inflammation and lipid peroxidation, reduce antioxidant defence, and cellular turnover. Further, HF diet would compromise placental capacity to adapt to infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Female C57BL/6J mice were fed a control (CON) or 62% HF diet six weeks before and throughout pregnancy and injected with poly(I:C) (viral mimic) or vehicle (VEH) 24 h before sacrifice at gestational days (GD) 12.5, 15.5, and 18.5 (<i>n</i> = 5–8/group/GD). Placental inflammasome (NLRP3), oxidative stress (4-HNE), antioxidant defence (GPx-4), and cellular proliferation-to-death ratio (Ki-67, Caspase-3) were assessed by immunohistochemistry, and mRNA expression of <i>Tlr3</i>, <i>Irf3</i>, <i>Tlr4</i>, <i>Tirap</i>, and <i>Il-1β</i> were measured by qPCR. Data were analysed by linear mixed models (<i>p</i> ≤ 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At GD12.5, infection was associated with increased <i>Tlr3</i> mRNA and immunoreactive (ir)-4-HNE, and reduced ir-GPx-4 expression in the placental labyrinth zone (LZ). By GD15.5, HF diet was associated with increased ir-NLRP3 in both LZ and junctional zones (JZ). Exposure to infection alone and co-exposure to HF diet and infection further increased LZ ir-NLRP3. At GD18.5, HF diet was associated with increased <i>Tirap</i> and <i>Il-1β</i> mRNA expression, ir-4-HNE in the JZ and ir-Caspase-3 in the LZ.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Maternal HF diet and infection exert distinct effects on the placenta across gestation, suggesting that maternal overnutrition might reduce the placenta's capacity to handle adverse exposures, which may increase susceptibility to poor fetal outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683184","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":"EVT-Derived Migrasomes Provide Mechanistic Insights Into Antiphospholipid Syndrome-Associated Recurrent Miscarriage","authors":"Di Wang,&nbsp;Yu Xie,&nbsp;Hongyuan Zhang,&nbsp;Tingting Dong,&nbsp;Xiaoyu Liu,&nbsp;Yilei Li,&nbsp;Yan Zhang,&nbsp;Xietong Wang,&nbsp;Qian Zhou","doi":"10.1111/aji.70272","DOIUrl":"https://doi.org/10.1111/aji.70272","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Recurrent miscarriage (RM) is a complex pregnancy-related disorder closely associated with impaired extravillous trophoblast (EVT). Antiphospholipid antibody syndrome (APS) is an autoimmune condition that contributes to adverse pregnancy outcomes, including RM. However, the mechanism by which APS induces RM remains largely unclear. Migrasomes, a newly identified type of extracellular vesicle generated during cell migration, may regulate cellular functions through the transfer of microRNAs (miRNAs). Increasing evidence has suggested that migrasomes play important roles in the female reproductive system, particularly in pregnancy-related disorders such as RM. This study aimed to explore the potential role and underlying mechanism of EVT-derived migrasomes in the pathogenesis of RM associated with APS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>First, EVT-derived migrasomes (EVTDMs) were isolated from an in vitro RM/APS model established in HTR-8/SVneo cells. Differentially expressed miRNAs in EVTDMs were identified by small RNA sequencing, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The predicted target gene of hsa-miR-206 was further validated using a dual-luciferase reporter assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results showed that migrasome markers were readily detected in EVTDMs derived from HTR-8/SVneo cells. An in vitro RM/APS model was established by co-incubation with anti-β2-glycoprotein I antibody (anti-β2-GPI Ab). Migrasome-like vesicles were identified by confocal microscopy and transmission electron microscopy. MiRNA profiling revealed that hsa-miR-206 was significantly upregulated in EVTDMs from the RM/APS group. Based on bioinformatic prediction and dual-luciferase reporter assays, IKBKB was identified as a direct binding target of hsa-miR-206.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, HTR-8/SVneo cells were capable of generating migrasome-like vesicles, and anti-β2-GPI Ab treatment altered the miRNA cargo of EVTDMs. Among the differentially expressed miRNAs, hsa-miR-206 was markedly upregulated and was validated to bind directly to the 3′UTR of IKBKB, suggesting a potential role in posttranscriptional regulation. However, the downstream functional consequences of this interaction remain to be further elucidated.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617158","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":"Altered Distribution of CD14+ Macrophages and Reduced ROS Activity in Preeclamptic Placentas","authors":"Luis Donis-Maturano,&nbsp;Judith Yenny Flores-Colque,&nbsp;Juana Calderon-Amador,&nbsp;Nidia Carolina Moreno-Corona,&nbsp;Oziel David Pérez-Luna,&nbsp;Orestes López-Ortega","doi":"10.1111/aji.70295","DOIUrl":"https://doi.org/10.1111/aji.70295","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Pregnancy requires a delicate balance between maternal immune tolerance and protective responses, with macrophages playing a pivotal role in placental development and immune regulation. Preeclampsia, a hypertensive disorder that affects 5%–8% of pregnancies, is associated with immune dysregulation, oxidative stress, and impaired placental remodeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>In this study, we investigated the distribution of CD14⁺ and CD11b⁺ cells and the production of reactive oxygen species (ROS) in placental tissues from healthy pregnancies and preeclampsia cases, from areas near the umbilical cord and the delivery channel and divided into maternal, maternal/fetal and fetal zones, of each area.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Immunofluorescence analysis revealed that in healthy placentas, CD14⁺ macrophages were heterogeneously distributed with enrichment in the fetal section near the delivery channel, whereas in preeclamptic placentas these cells accumulated predominantly in the umbilical cord region. No significant differences were observed for CD11b⁺ cells, although a tendency toward increased numbers was noted in preeclamptic tissues. ROS analysis showed no statistically significant changes, but preeclamptic placentas exhibited weaker fluorescence intensity, indicating reduced ROS activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that altered CD14⁺ and CD11b⁺ cells localization, together with diminished ROS signaling, may contribute to the pathophysiology of preeclampsia by impairing immune regulation and placental vascular remodeling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617157","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":"High Glucose Supplementation Aggravates Experimental Autoimmune Epididymo-orchitis via Localized Th17 Skewing in the Male Reproductive Tract","authors":"Jin-Chuan Liu,&nbsp;Qun-Xiong Zeng,&nbsp;Fu Shi,&nbsp;Jiangxia Shi,&nbsp;Xiaofeng Liu,&nbsp;Minmin Lyu,&nbsp;Yu Li,&nbsp;Emmanuele A. Jannini,&nbsp;Yong-Gang Duan","doi":"10.1111/aji.70300","DOIUrl":"https://doi.org/10.1111/aji.70300","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic epididymo-orchitis contributes significantly to male infertility through immune cell infiltration and pro-inflammatory cytokine elevation. High glucose intake promotes Th17 differentiation and autoimmunity, but its effects on autoimmune testicular inflammation remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To determine whether chronic high glucose supplementation exacerbates experimental autoimmune epididymo-orchitis (EAEO), impairs spermatogenesis, and drives CD4⁺ T-cell dysregulation, particularly Th17 polarization, in the reproductive tract.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>EAEO was induced in male C57BL/6 mice with or without chronic 10% glucose supplementation in drinking water. Sperm parameters, ROS levels, apoptosis, and histopathology were evaluated. CD4⁺ T-cell subsets (Th1, Th17, Treg, TNF-α⁺ effector memory) were quantified by flow cytometry in testis, epididymis, spleen, and testicular inguinal lymph nodes (iLN) at days 30, 60, and 90 post-immunizations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>High glucose intake accelerated EAEO progression, markedly worsening sperm concentration and motility, elevating sperm ROS, increasing germ cell apoptosis, and causing severe histopathological damage. In the reproductive tract, glucose induced an upward trend of CD4⁺ T cells and late-phase selective Th17 skewing (days 60–90), with significant IL-17A⁺CD4⁺ Teff increases and accompanying TNF-α⁺CD4⁺CD44⁺ Teff upregulation, while IFN-γ⁺ Th1 responses remained modest. These pro-inflammatory changes were strictly localized, with no significant Th17, Th1, Treg, or TNF-α alterations in spleen or iLN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion and Conclusion</h3>\u0000 \u0000 <p>Chronic high glucose exacerbates EAEO by intensifying oxidative stress, apoptosis, and tissue injury while promoting a late-phase, tissue-restricted Th17-biased CD4⁺ T-cell response in the testis and epididymis. These findings reveal a metabolic-immune axis that may accelerate immune-mediated male subfertility via localized Th17 mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617161","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":"Persistence of SARS-CoV-2 RNA Residues in Placenta Tissue Following Maternal COVID-19 Infection During Pregnancy","authors":"Yang Gu,&nbsp;Jie Xu,&nbsp;Xin Gu,&nbsp;David F. Lewis,&nbsp;Krista Queen,&nbsp;Rona S. Scott,&nbsp;Dani Zoorob,&nbsp;John Vanchiere,&nbsp;Yuping Wang","doi":"10.1111/aji.70302","DOIUrl":"https://doi.org/10.1111/aji.70302","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Prolonged SARS-CoV-2 viral persistence was reported in extrapulmonary tissues in patients infected with COVID-19. SARS-CoV-2 can infect placental tissue. However, little is known about SARS-CoV-2 viral persistence in the placenta.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>This is a retrospective and IRB approved study. Placental tissue samples from 40 women infected with COVID-19 at various gestational age were analyzed. SARS-CoV-2 RNA expression was examined by in situ hybridization on placental disk and fetal membrane. S-protein and N-protein expression was determined by immunostaining. SARS-CoV-2 RNA sequencing was also performed in 12 out of the 29 cases in which SARS-CoV-2 RNA expression was detected positive by in situ hybridization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SARS-CoV-2 RNA expression was detected in placental disk, predominantly localized in syncytiotrophoblasts in 29 out of the 40 cases, but not in fetal membrane. Among the 29 positive cases, 4 infected in the first trimester, 7 in the second trimester, and 18 in the third trimester or at term. The longest interval from infection to delivery was 221 days. Among the 21 women who tested positive for COVID-19 at L/D admission, 18 (85.7%) detected SARS-CoV-2 RNA expression in placental tissue. Notably, 11 (57.9%) of 19 cases (negative test at L/D admission) detected viral RNA expression in placental villous tissue. Viral RNA expression was also detected in villous core vessel endothelium in two COVID (+) newborn placentas, with corresponding positive S-protein and N-protein expression in syncytiotrophoblasts. S-protein and N-protein expression was undetectable in 27 out of the 29 cases with positive detection of SARS-CoV-2 RNA expression. Partial RNA-dependent RNA polymerase (RdRp) region sequence was identified in all the 12 cases examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings provide compelling evidence that SARS-CoV-2 genetic material can persist in placental tissue long after maternal infection, which may potentially contribute to a sustained inflammatory environment at the maternal-fetal interface during pregnancy. The phenomenon of partial RdRp sequence detected would provide a possible explanation for undetectable S- and N-protein expression in testing specimens.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617162","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":"Alterations in Cellular Immunity in Patients With Endometriosis: Systematic Review and Meta-Analysis","authors":"Leila Adamyan,&nbsp;Laura Pivazyan,&nbsp;Kristina Kurbatova,&nbsp;Sona Barsegyan,&nbsp;Karina Mailova,&nbsp;Assia Stepanian","doi":"10.1111/aji.70296","DOIUrl":"https://doi.org/10.1111/aji.70296","url":null,"abstract":"<div>\u0000 \u0000 <p>Determining the pathogenesis of endometriosis remains a major challenge in contemporary gynecology, and the investigation of alterations in cellular immunity may provide important insights into this issue. A comprehensive search of electronic databases (PubMed, The Cochrane Library, ClinicalTrials.gov, Scopus, Embase, and Google Scholar) identified 24 studies meeting the inclusion criteria for qualitative synthesis. The primary analysis compared the concentration of IL-4 in peripheral blood (MD = 1.32, 95% CI: −15.00 to 17.63, <i>p</i> = 0.87); the secondary compared the concentration of HLA-DR⁺-macrophages (MD = −2.62, 95% CI: −8.98 to 3.73, <i>p</i> = 0.42) and HLA-ABC⁺-macrophages (MD = −6.84, 95% CI: −23.94 to 10.26, <i>p</i> = 0.43) in peritoneal fluid; the third compared the IL-6 concentration in peritoneal fluid (MD = 338.00, 95% CI: 85.02 to 590.98, <i>p</i> = 0.009); the fourth compared the NK-cell level in peritoneal fluid (MD = 6.75, 95% CI: −12.42 to 25.91, <i>p</i> = 0.49); the fifth compared the level of NK-cells in ectopic and eutopic endometrium (MD = −9.12, 95% CI: −24.39 to 6.15, <i>p</i> = 0.24) between endometriosis and control groups. Overall, the included studies suggest that signaling pathways involving T lymphocytes, monocytes, macrophages, and natural killer cells are altered in patients with endometriosis.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617159","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":"Natural Products Targeting Oxidative Stress–Inflammation Crosstalk in Endometriosis","authors":"Divya Mhatre,&nbsp;Tanvi Jadhav,&nbsp;Sanket Shirodkar,&nbsp;Gaurav Doshi","doi":"10.1111/aji.70293","DOIUrl":"10.1111/aji.70293","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Endometriosis is a chronic, estrogen-dependent inflammatory disorder marked by ectopic endometrial-like tissue growth, resulting in pelvic pain, infertility, and significant declines in quality of life. Despite extensive research, current therapies remain largely symptomatic and are often associated with recurrence, hormonal adverse effects, and compromised fertility outcomes. Growing evidence indicates that oxidative stress, chronic inflammation, mitochondrial dysfunction, altered immune surveillance and metabolic dysregulation are central drivers of lesion establishment and progression. However, these interconnected mechanisms are often examined in isolation, limiting translational progress.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>We provide a comprehensive, integrative analysis of the molecular and cellular pathways underlying endometriosis, with particular emphasis on oxidative stress–inflammation crosstalk, signalling cascades supporting lesion survival, and emerging metabolic and mitochondrial targets. By critically synthesising recent experimental, preclinical, and clinical findings, this review highlights mechanistic overlaps that may explain therapeutic resistance and disease recurrence. Furthermore, it evaluates novel pharmacological and nutraceutical interventions targeting redox imbalance, inflammatory mediators, and intracellular signalling pathways, thereby expanding the conceptual framework beyond conventional hormonal suppression. Rising global endometriosis prevalence and its socioeconomic burden necessitate a shift from purely symptomatic management to mechanism-driven therapeutic strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This review addresses that gap by consolidating dispersed evidence into a unified mechanistic perspective, identifying promising translational targets, and proposing future research directions. The insights provided will help in creating safer, fertility-preserving and more durable treatments. Thus, we categorise natural products by: (1) translational development stage (in vitro to clinical candidate); (2) regulatory pathway (dietary supplement, herbal medicine, or pharmaceutical); and (3) clinical context (e.g., pain control, recurrence prevention, or fertility preservation). Conclusion: This structured, clinically-oriented framework distinguishes the present synthesis from mechanistic reviews and serves to guide both future research design and rational integration of natural products into endometriosis therapeutic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576778","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":"Ferroptosis-Mediated Placental Dysfunction in the Pathophysiology of Gestational Diabetes Mellitus","authors":"S Monisha,&nbsp;K L Milan,&nbsp;M Anuradha,&nbsp;K M Ramkumar","doi":"10.1111/aji.70288","DOIUrl":"https://doi.org/10.1111/aji.70288","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy associated with adverse maternal and fetal outcomes. Nevertheless, the molecular mechanism of placental dysfunction in GDM are still not clear, especially the role of ferroptosis and its interplay with oxidative stress, inflammation, and angiogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Placental tissues from GDM pregnancies were examined to assess oxidative stress, antioxidant defense, ferroptosis regulation, inflammatory signaling, and angiogenic pathways. Expression levels of key molecular markers were evaluated, and correlation analyses were performed to identify mechanistic interrelationships.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>GDM placenta demonstrated elevated oxidative stress markers, including P22PHOX and TXNIP, accompanied by reduced antioxidant markers, such as HO-1, NQO1, SOD2, and CAT, indicating impaired cellular defense. Ferroptosis regulation was disrupted, as anti-ferroptotic markers GPX4, SLC7A11, and NRF2 were significantly downregulated, while pro-ferroptotic markers TFR1 and ACSL4 were increased, suggesting enhanced iron accumulation and lipid peroxidation. This was accompanied by heightened inflammation, evidenced by increased IL-6, IL-1β, TNF-α, and NF-κB activation, alongside reduced IL-10 expression. Furthermore, angiogenesis was impaired, reflected by decreased VEGFA, HIF-1α, and SDF-1α levels, highlighting poor vascular development in the placenta. Additionally, Correlation analyses demonstrated strong associations between ferroptosis markers and oxidative stress, inflammatory, and angiogenic pathways, suggesting the possible presence of an interconnected regulatory network.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings identify ferroptosis as a central regulator of GDM-associated placental dysfunction, through a possible interconnected network of oxidative stress, inflammation, and impaired angiogenesis. Targeting ferroptosis may offer a possible therapeutic option to restore placental function and improve maternal-fetal outcomes in GDM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467203","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":"The HIV Reservoir and Immune Landscape Across the Life Course of Women: Implications for Cure Strategies","authors":"Elizabeth Hastie,&nbsp;Priya Khetan,&nbsp;Sarah A. LaMere,&nbsp;Ashley F. George,&nbsp;Rebecca Abelman,&nbsp;Kathleen Weber,&nbsp;Phyllis C. Tien,&nbsp;Judith D. Auerbach,&nbsp;Maile Karris,&nbsp;Todd Brown,&nbsp;Jonathan Karn,&nbsp;Loreen Willenberg,&nbsp;Dawn Averitt,&nbsp;Bridgette Picou,&nbsp;Nadia R. Roan,&nbsp;Eileen P. Scully,&nbsp;Karine Dubé,&nbsp;Nancie Archin,&nbsp;Sara Gianella","doi":"10.1111/aji.70279","DOIUrl":"https://doi.org/10.1111/aji.70279","url":null,"abstract":"<p>Sex hormones and reproductive transitions profoundly shape immune, metabolic, neuropsychological, and mucosal biology, as well as HIV persistence, across women's lives. Although women constitute the majority of people with HIV worldwide, hormonal and reproductive biology are still not sufficiently incorporated into HIV cure research. Cisgender women, transgender women on gender-affirming hormone therapy (GAHT), and gender-diverse individuals assigned female at birth are underrepresented in cure studies, despite experiencing unique and changing hormonal states that influence estrogen signaling, tissue-specific hormone exposure, and immune function. Estradiol, progesterone, and hormone-based therapies, including contraception, GAHT, and menopausal hormone therapy, influence innate and adaptive immunity, inflammatory responses, epithelial barrier function, and cardiometabolic and neurocognitive pathways. These processes also shape tissue-specific HIV reservoir formation and maintenance, modulate proviral transcription, and affect immune effector functions. However, most HIV cure strategies have been developed without systematically considering these hormone-dependent mechanisms, which limits mechanistic understanding, broad applicability, and translational relevance. In this review, we synthesize emerging evidence at the intersection of reproductive endocrinology and HIV immunovirology, identify critical knowledge gaps, and propose priorities for life-course, hormone-informed HIV cure strategies. We argue that meaningful inclusion of women and gender-diverse individuals is essential not only for ethically grounded, equity-centered, community-engaged research practices but also for the scientific rigor needed to achieve durable ART-free virologic control and cure.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70279","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467369","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}