{"title":"Integrative Analyses of Biomarkers and Pathways in Oxidative Stress-Related Genes for Gestational Diabetes Mellitus","authors":"Yunyan Chen, Fuchu Qian, Yingying Chen","doi":"10.1111/aji.70052","DOIUrl":"10.1111/aji.70052","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Oxidative stress (OS) plays a key role in the pathogenesis of gestational diabetes mellitus (GDM), but it was not well understood. We aimed to investigate the biomarkers and underlying mechanisms of OS-related genes in GDM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>The GSE103552 and GSE70493 datasets of GDM were acquired from the Gene Expression Omnibus (GEO) database. Then, oxidative stress-related differentially expressed genes (OSDEGs) were screened between GDM and normal samples from these two datasets. Further analyses were conducted by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene set enrichment analysis (GSEA) for these OSDEGs. Subsequently, protein-protein interaction (PPI) network analyses of these OSDEGs were carried out to screen the hub genes. Eventually, we used single-sample Gene-set enrichment analysis (ssGSEA) to compare the immune cell infiltration between GDM and normal samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 26 OSDEGs. Enrichment analysis suggested that the OSDEGs enriched in OS and diabetes-related pathways. GSEA revealed that these OSDEGs enriched in sensory perception of taste and negative regulation of notch4 signaling pathways. Moreover, PPI analysis showed that 15 OSDEGs were the hub gene in GDM. A total of 14 hub genes were highly expressed in GDM and might be used as diagnosis biomarkers. Moreover, many potential agents might target 10 hub genes for GDM treatment. In addition, immune infiltrate analyses revealed that expression of 14 hub genes was positively correlated to immune infiltrates in GDM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>OSDEGs are significant in GDM and may provide potential diagnostic biomarkers and treatment targets for GDM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057469","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}
Xing Su, Wan-Ying Yu, Ming-Jia Zhao, Yi Hu, Ying Li, Xue-Qin Wang, Lu Zhang, Xiao-Dan Lv, Xu Ma, Hong-Fei Xia
{"title":"MiR-423 Coding Region Genetic Polymorphism rs8067576 May Associate With the Risk of Developing Recurrent Spontaneous Abortion: A Case-Control Study in a Chinese Han Population","authors":"Xing Su, Wan-Ying Yu, Ming-Jia Zhao, Yi Hu, Ying Li, Xue-Qin Wang, Lu Zhang, Xiao-Dan Lv, Xu Ma, Hong-Fei Xia","doi":"10.1111/aji.70050","DOIUrl":"10.1111/aji.70050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Our previous study has identified an association of a single nucleotide polymorphism (SNP) in the <i>miR-423</i> gene with recurrent spontaneous abortion (RSA). The presence of additional RSA-linked SNPs in the <i>miR-423</i> gene remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We evaluated polymorphisms in the coding region of <i>miR-423</i> in Han Chinese women with unexplained RSA (URSA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant differences were observed in the genotype and allele distribution of <i>miR-423</i> rs8067576 between patients with RSA and control subjects. A robust association was found between an elevated RSA incidence and the presence of A/T heterozygosity in <i>miR-423</i> rs8067576, with an odds ratio (OR) of 1.76 (95% confidence interval [CI]: 1.26 to 2.47, <i>p</i> = 0.000292). The rare allele <i>T</i> in the pre-<i>miR-423</i> sequence was shown to cause a discernible structural change and a reduced ΔG value. Compared with the <i>A</i> allele, the rare <i>T</i> allele promoted cell proliferation. Furthermore, compared with the <i>T</i> allele, the <i>A</i> allele in the rs8067576 polymorphism exhibited a greater ability to inhibit the translation of proliferation-associated 2 group 4 (Pa2g4), which is the functional target of <i>miR-423</i>. The <i>T</i> allele in the rs8067576 polymorphism was also found to be more susceptible to the inhibition of cell proliferation induced by mifepristone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The rs8067576 <i>A</i> > <i>T</i> polymorphism in the <i>miR-423</i> gene may serve as a genetic susceptibility locus for RSA. This polymorphism appears to contribute to an increased risk of acquiring URSA in humans by destroying mature <i>miR-423</i>.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051272","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}
Kyle S. Wiley, Laura E. Martínez, Daylon Kwon, Delaney A. Knorr, Marta Epeldegui, Molly M. Fox
{"title":"Regulatory B-Cells Are Associated Negatively With Regulatory T-Cells and Positively With Cytokines in Peripheral Blood of Pregnant Women","authors":"Kyle S. Wiley, Laura E. Martínez, Daylon Kwon, Delaney A. Knorr, Marta Epeldegui, Molly M. Fox","doi":"10.1111/aji.70027","DOIUrl":"10.1111/aji.70027","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Regulatory B-cells (Bregs, CD19<sup>+</sup>CD24<sup>hi</sup>CD38<sup>hi</sup>) are a specialized B-cell subset that suppresses immune responses and potentially contribute to the maintenance of an immune-privileged environment for fetal development during pregnancy. However, little is known about the surrounding immunological environment of Bregs in gestational physiology. The relationship of regulatory T-cells (Tregs, CD4<sup>+</sup>CD25<sup>hi</sup>CD127<sup>lo</sup>FoxP3<sup>+</sup>) to Bregs in coordinating immunoregulation during pregnancy is unknown. We aimed to determine whether peripheral concentrations of Bregs and/or PD-L1-expressing Bregs correlated with Tregs and cytokines during pregnancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>Peripheral blood samples were obtained from 29 pregnant women at mean 12 weeks’ gestation. Participants were age ≥ 18, self-identified as Latina/Hispanic, and <i>N</i> = 12 primigravid. Peripheral blood mononuclear cells were isolated, stained, and analyzed by flow cytometry to determine percentages of Tregs from CD4<sup>+</sup> T-cells and five Treg subsets defined by immune checkpoint markers, and Bregs and PD-L1<sup>+</sup> Bregs from total B-cells. Levels of 13 cytokines were measured on a Meso Scale Discovery multiplex platform.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Bregs positively correlated with pro-inflammatory cytokine interleukin (IL)-6. PD-L1<sup>+</sup> Bregs positively correlated with T-cell suppressive cytokine IL-10. PD-L1<sup>+</sup> Bregs negatively correlated with Tregs and Helios<sup>+</sup>, CTLA-4<sup>+</sup>, PD-1<sup>+</sup>, TIGIT<sup>+</sup>, and TIM3<sup>+</sup> Tregs. For primigravida, PD-L1<sup>+</sup> Bregs correlated positively with IL-10 and negatively with Helios<sup>+</sup> and TIGIT<sup>+</sup> Tregs. For multigravida, PD-L1<sup>+</sup> Bregs correlated positively with IL-8 and negatively with Helios<sup>+</sup>, CTLA-4<sup>+</sup>, PD-1<sup>+</sup>, and TIGIT<sup>+</sup> Tregs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study provides insight into the immunosuppressive role of Bregs and PD-L1<sup>+</sup> Bregs during human pregnancy. Our results suggest that PD-L1<sup>+</sup> Bregs can employ suppressive mechanisms to limit pro-inflammatory responses in primigravida.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031701","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}
Amber E. M. Lombardi, Denise H. J. Habets, Salwan Al-Nasiry, Marc E. A. Spaanderman, Lotte Wieten
{"title":"Natural Killer Cell Education in Women With Recurrent Pregnancy Loss","authors":"Amber E. M. Lombardi, Denise H. J. Habets, Salwan Al-Nasiry, Marc E. A. Spaanderman, Lotte Wieten","doi":"10.1111/aji.70045","DOIUrl":"10.1111/aji.70045","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Natural killer (NK) cells undergo education for full functionality via interactions between killer immunoglobulin-like receptors (KIRs) or NKG2A and human leukocyte antigen (HLA) ligands. Presumably, education is important during early pregnancy as insufficient education has been associated with impaired vascular remodeling and restricted fetal growth in mice. NK cell education is influenced by receptor co-expression patterns, human cytomegalovirus (CMV), the HLA-E<sup>R</sup>107<sup>G</sup> dimorphism, and HLA-B leader peptide variants. We hypothesized altered NK cell education status and differences in frequencies of HLA-E genotypes and HLA-B leader peptide variants in women with recurrent pregnancy loss (RPL) compared to women with previously uncomplicated pregnancies, and between CMV seropositive and seronegative RPL women.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods of Study</h3>\u0000 \u0000 <p>Peripheral blood mononuclear cells were analyzed by flow cytometry. HLA-ABC was typed by sequence-specific oligonucleotide PCR, and HLA-E by Sanger sequencing. CMV status was determined by anti-CMV IgG immunoassay. NK cells were considered “educated” if the HLA ligand to a KIR or NKG2A was present.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>KIR/NKG2A co-expression patterns and percentages of educated NK cells were similar between RPL and controls, and between seropositive and seronegative RPL women. Frequencies of HLA-E genotypes and HLA-B leader peptide variants were comparable. RPL women with the HLA-B T/T variant had a lower percentage of NKG2A-educated NK cells (47.8%) compared to controls (66.4%) (<i>p</i> = 0.025).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>HLA-B leader peptide variants might impact NKG2A-specific NK cell education in RPL, warranting validation in larger studies. Follow-up studies are needed to investigate the education status of uterine NK cells and their role in pregnancy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031725","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}
Aline de Oliveira Santos, Debora Hipolito Quadreli, Glaura Scantamburlo Alves Fernandes, Luis Souza Lima de Souza Reis, Marcela de Andrade Bernal Fagiani, Lauren Chrys Soato Marin, Victor Rogério Garcia Batista, Giovana Rampazzo Teixeira, Patrik Junior de Lima Paz, Caliê Castilho, Mayara de Oliveira Vidotto Figueiredo, Ines Cristina Giometti
{"title":"Quercetin Supplementation Reduces Oxidative Stress in the Testes of Wistar Rats Fed a High-Fat Diet","authors":"Aline de Oliveira Santos, Debora Hipolito Quadreli, Glaura Scantamburlo Alves Fernandes, Luis Souza Lima de Souza Reis, Marcela de Andrade Bernal Fagiani, Lauren Chrys Soato Marin, Victor Rogério Garcia Batista, Giovana Rampazzo Teixeira, Patrik Junior de Lima Paz, Caliê Castilho, Mayara de Oliveira Vidotto Figueiredo, Ines Cristina Giometti","doi":"10.1111/aji.70048","DOIUrl":"10.1111/aji.70048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>A high-fat diet (HFD) predisposes animals to glucose intolerance, dyslipidemia and testicular oxidative stress, and impairs sperm production in rats. Quercetin is a flavonoid with antioxidant, anti-inflammatory, and lipolytic actions and is a potential supplement to combat the oxidative stress caused by HFD and its harmful effects on reproduction. This study evaluated the effects of quercetin supplementation at doses of 10 and 20 mg/day on reproductive parameters and testicular oxidative stress in Wistar rats fed a diet rich in pork fat and fructose.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of study</h3>\u0000 \u0000 <p>The rats received a basal diet or HFD for 2 months, after which the animals fed the HFD received daily supplementation of 0, 10, or 20 mg of quercetin for another 2 months. Oxidative stress, histological alterations, and the expression of oxidative, inflammatory, and apoptotic mediators in the testes were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Animals fed the HFD had a lower dietary intake and body, epididymis, and duct weights, regardless of the presence of quercetin. There were no changes in testicular weight, germinal epithelium diameter, sperm motility and morphology, or expression of testicular inflammatory genes (<i>p </i>> 0.05). There was a reduction in the oxidative stress index and oxidized glutathione in rats that received the HFD and 20 mg of quercetin compared with the HF group without quercetin. No difference was observed in the expression of BAX, BCL2, TNFα, caspase 3, or AR between the groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Daily quercetin supplementation dose-dependently reduces testicular oxidative stress in Wistar rats fed a diet rich in pork fat and fructose.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998504","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}
Nandini Goel, Madeline C. Baker, Michael T. Aboujaoude, Michael J. Diaz, Rahul Jain, Taha I. Huda, Andrea Chobrutskiy, Boris I. Chobrutskiy, Joanna J. Song, Veda Naga Priya Vangala, George Blanck
{"title":"Better Outcomes for Ovarian Cancer Associated With the Detection of Anti-EBV TCR CDR3s: Potential Relevance to Diffuse Large B-Cell Lymphoma","authors":"Nandini Goel, Madeline C. Baker, Michael T. Aboujaoude, Michael J. Diaz, Rahul Jain, Taha I. Huda, Andrea Chobrutskiy, Boris I. Chobrutskiy, Joanna J. Song, Veda Naga Priya Vangala, George Blanck","doi":"10.1111/aji.70046","DOIUrl":"10.1111/aji.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Given the ongoing challenges regarding the specific roles of viral infections in cancer etiology, or as cancer co-morbidities, this study assessed potential associations between anti-viral, T-cell receptor (TCR) complementarity domain region-3 (CDR3s), and clinical outcomes for ovarian cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>TCR CDR3s were isolated from ovarian cancer specimens for a determination of which patients had anti-viral CDR3s and whether those patients had better or worse outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Analyses revealed that patients with exact matches of anti-Epstein–Barr virus (EBV) CDR3 amino acid sequences exhibited better outcomes for both overall and disease-specific survival. However, better outcomes were not observed when assessing anti-viral CDR3s representing cytomegalovirus, influenza A, or Sars-CoV-2. Due to previous occurrences of the occasional misdiagnoses of lymphoma as ovarian cancer, the frequency of anti-EBV CDR3s in lymphoma patients was determined. These frequencies were relatively high, particularly for diffuse large B-cell lymphoma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings (i) underscore the potential value of anti-EBV immune responses in terms of patient outcomes; (ii) raise questions about the potential value of anti-EBV immunotherapies; and (iii) support further inquiry into the relationship between EBV infection and previously reported cases of ovary-resident lymphoma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998502","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}
Gizem Aktemur, Betül Tokgöz Çakır, Gülşan Karabay, Ahmet Arif Filiz, Zeynep Seyhanlı, Serap Topkara Sucu, Nazan Vanlı Tonyalı, Şevki Çelen
{"title":"Second-Trimester Inflammatory Markers in Predicting Fetal Growth Restriction: A Retrospective Analysis","authors":"Gizem Aktemur, Betül Tokgöz Çakır, Gülşan Karabay, Ahmet Arif Filiz, Zeynep Seyhanlı, Serap Topkara Sucu, Nazan Vanlı Tonyalı, Şevki Çelen","doi":"10.1111/aji.70047","DOIUrl":"10.1111/aji.70047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem:</h3>\u0000 \u0000 <p>Fetal growth restriction (FGR) is a critical pregnancy complication linked to increased perinatal morbidity and mortality. Inflammation plays a key role in FGR's pathophysiology, and systemic inflammation markers may serve as predictors. This study evaluates the role of various inflammation indices; systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), pan-immune-inflammation value (PIV), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), lymphocyte-to-platelet ratio (LMR), monocyte-to-platelet ratio (MPR), aggregate systemic inflammation index (AISI), systemic coagulation inflammation index (SCII), and immature granulocyte percentage (IG%) in predicting FGR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods of Study</h3>\u0000 \u0000 <p>This retrospective study included 403 pregnant women treated at Ankara Etlik City Hospital between August 2022 and May 2024. The study population comprised 202 women with uncomplicated pregnancies (control group) and 201 women diagnosed with FGR per the Delphi Consensus Criteria. Second-trimester blood samples were used to calculate the inflammatory indices.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SII and NLR levels were significantly higher in the FGR group compared to controls (<i>p</i> = 0.020, <i>p</i> = 0.028, respectively). However, no significant associations were found between these indices and adverse neonatal outcomes. Cut-off values for SII and NLR were 896 and 3.91, respectively, with moderate sensitivity and specificity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SII and NLR, measured in the second trimester, may be useful in predicting FGR. Although these indices did not correlate with adverse neonatal outcomes, further prospective studies with larger populations are needed to validate their clinical utility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998515","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}
Yang Liu, Xianping Hou, Zhangwei Jia, Shaotong Zhao, Tingting Zhou, Jia Liao, Qian Zhang, Junhao Yan, Tianxiang Ni
{"title":"Association of Arachidonic Acid Metabolism Related Genes With Endometrial Immune Microenvironment and Oxidative Stress in Coupes With Recurrent Implantation Failure","authors":"Yang Liu, Xianping Hou, Zhangwei Jia, Shaotong Zhao, Tingting Zhou, Jia Liao, Qian Zhang, Junhao Yan, Tianxiang Ni","doi":"10.1111/aji.70044","DOIUrl":"10.1111/aji.70044","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alterations in lipid metabolism were reported to impact human fertility; however, there is limited evidence on the association of lipid metabolism with embryo implantation as well as the etiology of recurrent implantation failure (RIF), especially regarding arachidonic acid metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Experimental verification research (16 RIF patients and 30 control patients) based on GEO database analysis (24 RIF patients and 24 control patients). The methods in bioinformatics included differential gene screening, functional enrichment analysis, protein-protein interaction network, cluster analysis, weighted gene co-expression network analysis, and so forth. RIF patients were recruited for the experimental validation section. The endometrial samples in the mid-luteal phase were collected and subjected to quantitative real-time PCR detection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Genes related to oxidative stress were differentially expressed and 17 different types of immune cells exhibited diverse infiltration in three RIF subgroups with different arachidonic acid metabolism. HPGDS, ALOX12, and TBXAS1 showed a strong positive correlation with the infiltration of NK cell, on the contrary, GGT6, PLA2G12A, and PTGS2 showed a strong negative correlation. The overall expression of AAMRGs was positively correlated with the infiltration of activated CD8 T cell, macrophage, natural killer cell, and T follicular helper cell.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The cluster of arachidonic acid metabolism-related genes (AAMRGs) was abnormally expressed and positively associated with excessive oxidative stress as well as extensive infiltration of immune cells, including NK cells among RIF patients. Considering the high heterogeneity of the etiology of RIF, our study utilized the expression of AAMRGs as a typing basis to provide a new understanding of endometrial receptivity from the perspective of lipid metabolism and immune regulation in unexplained RIF couples, providing directions for its etiology and future basic research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969501","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}
Dor Marciano, Eyal Sheiner, Ruslan Sergienko, Tamar Wainstock
{"title":"The Association Between Maternal Preeclampsia and Risk for Offspring Infectious Diseases–A Sibling Matched Analysis","authors":"Dor Marciano, Eyal Sheiner, Ruslan Sergienko, Tamar Wainstock","doi":"10.1111/aji.70041","DOIUrl":"10.1111/aji.70041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Preeclampsia is a severe, multisystem complication that affects 2%–5% of pregnancies, and is a leading cause of fetal and maternal morbidity and mortality worldwide. Preeclampsia may have devastating results on maternal health and may affect offspring's immediate and long-term health. Previous studies have examined the impact of maternal preeclampsia on the long-term health outcomes of offspring, many of these studies have been limited by confounding factors that could bias the results. The classic way of analyzing the relationship between maternal preeclampsia and long-term infectious morbidity of the offspring, which typically involves comparing the rates of infectious disease hospitalization between the exposed and unexposed groups, may not be sufficient due to the potential influence of unmeasured confounding factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To study the association between maternal preeclampsia and long-term offspring infectious morbidity, while employing sibling-matched analysis to maximize confounder control.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Study design</h3>\u0000 \u0000 <p>A retrospective cohort was conducted, including parous women, who were diagnosed with preeclampsia in one pregnancy. A sibling-matched analysis was performed, so that one sibling was, and the other was not, prenatally exposed to maternal preeclampsia. Incidence of the offspring hospitalization with infectious morbidities were compared between the siblings, as well as the time to first hospitalization with such a diagnosis. Multivariable survival analysis was performed to adjust for confounding variables.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Offspring of mothers with preeclampsia (<i>n</i> = 4272) were significantly (<i>p</i> < 0.001) at a higher risk for long-term infectious hospitalization compared to offspring of mothers without preeclampsia (n = 4272), with a hazard ratio of 1.324 (95% CI 1.168–1.503) after adjusting for maternal age, gestational age, and mode of delivery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Offspring born following pregnancies complicated with preeclampsia are at increased risk for infectious morbidity, even while rigorously adjusting for confounders in a sibling analysis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11722688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962022","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":"Thyroid Autoimmunity: The Treatment of Hashimoto's Disease, or the Presence of Antithyroid Antibodies Alone, in Pregnancy","authors":"Jonathan Scher, Carmen Dabao, Caitlin Rukat","doi":"10.1111/aji.70042","DOIUrl":"10.1111/aji.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Hashimoto's disease is the commonest autoimmune disease of pregnancy. The presence of Anti-Thyroid antibodies (ATAs) alone [subclinical hypothyroidism] has also been shown to have adverse pregnancy effects. These can result in failure to conceive, recurrent miscarriages, anemia, preeclampsia, and abruption. Hashimoto's disease in reproduction can cause difficulty in conception through hormonal interference. It can also cause miscarriages, growth retardation, and preterm birth. The current recommended treatment is the administration of levothyroxine. This corrects the thyroid balance and may relieve the patient's hypothyroid symptoms. However, repeated recent studies have shown that it is no more effective than a placebo in correcting obstetric complications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>As a result, we decided to use an anti-autoimmune-directed treatment for this disorder. We selected to use IVIG for both its known powerful anti-inflammatory and anti-autoimmune benefits. There are several studies and observational reports in the literature on the use of IVIG in pregnancy for treating recurrent miscarriages and repeated failed IVF. However, there are no reports in the literature on using IVIG to treat Hashimoto's disease, or the presence of ATAs alone, in pregnancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study showed an increase in live births in the IVIG-treated group versus the non-IVIG-treated group after adjustment for maternal age at delivery (OR = 4.6, 95% CI (1.1, 18.1)). There were no adverse effects in the patients who received IVIG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>IVIG is effective in significantly improving the obstetric outcome in patients with Hashimoto's disease, or the presence of ATAs alone.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962025","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}