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}
Silvia D'Ippolito, Filippo Gavi, Chiara Granieri, Chiara De Waure, Sara Giuliano, Francesco Cosentino, Chiara Tersigni, Giovanni Scambia, Nicoletta Di Simone
{"title":"Efficacy of Corticosteroids in Patients With Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis","authors":"Silvia D'Ippolito, Filippo Gavi, Chiara Granieri, Chiara De Waure, Sara Giuliano, Francesco Cosentino, Chiara Tersigni, Giovanni Scambia, Nicoletta Di Simone","doi":"10.1111/aji.70037","DOIUrl":"10.1111/aji.70037","url":null,"abstract":"<div>\u0000 \u0000 <p>Recurrent pregnancy loss (RPL) represents a complication of pregnancy occurring in 1%–3% of all couples trying to conceive. About 50%–60% of RPL cases remain idiopathic, therefore therapeutic strategies seem empirical and based on unproven evidence. We investigated the efficacy of corticosteroids in women with RPL. We conducted a systematic review and meta-analysis, up to August 2024, in the PubMed, Scopus, and Web of Science databases, including studies on idiopathic RPL women and comparing corticosteroids versus control treatment. Primary outcome was the ongoing pregnancy rate beyond 12 weeks of gestation; secondary outcomes were live birth rate (LBR), stillbirth, birth weight, incidence of preeclampsia and/or gestational diabetes, gestational age at delivery, and fetal abnormalities. Four studies comprising 417 RPL women randomly assigned to steroid or control treatment were included. We found that oral corticosteroids significantly increase the ongoing pregnancy rate beyond 12 weeks of gestation compared to the control group (log OR [odds ratio] = 1.49 [0.32, 2.67], <i>p</i> = 0.01), with high heterogeneity (<i>I</i><sup>2</sup> = 75%), and improve LBR (log OR = 0.9 [0.11, 1.69], <i>p</i> = 0.03), with low heterogeneity (<i>I</i><sup>2</sup> = 0.05%). However, the limited number of studies significantly limits the strength of the findings. Also, the benefit/risk assessment of the use of corticosteroids in early pregnancy for RPL is still unclear.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942757","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":"FOXL2 Knockdown Inhibits the Progression of Endometriosis","authors":"Bing Zhang, Shang-Jin Li, Hua Yuan, Shan-Shan Cong, Shao-Jie Zhao, Xiao-Jun Yang","doi":"10.1111/aji.70043","DOIUrl":"10.1111/aji.70043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Endometriosis (EM) is known as a common estrogen-dependent chronic inflammatory disease. Elevated levels of Forkhead box L2 (FOXL2) have been observed in uterine diseases, including EM. However, the molecular mechanism of FOXL2 in EM needs to be further illustrated. This study aimed to investigate the regulatory role of FOXL2 in EM rats and isolated ectopic endometrial stromal cells (EC-ESCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>FOXL2 knockdown were designed to evaluate the effects of FOXL2 in EM model rats and EC-ESCs. Hematoxylin-eosin (HE) staining was used to evaluate the pathological morphology of ectopic endometrium. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) analysis and immunohistochemistry (IHC) were applied to detect the expression of FOXL2, EM-related genes, and epithelial to mesenchymal transition-related proteins. The proliferation, migration, invasion, and apoptosis of EC-ESCs were determined by 5-ethynyl-2′-deoxyuridine (EDU) assay, Transwell assay, and flow cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The FOXL2 level was remarkably higher in the ectopic endometrial tissue than that in the normal endometrial tissue. Knockdown of FOXL2 notably improved the pathological morphology of EM in rats, and decreased expression levels of ER-α, ER-ß, and Cyp19a. Additionally, down-regulation of FOXL2 suppressed cells proliferation, migration and invasion, and stimulated more apoptotic cells in EC-ESCs. Besides, FOXL2-small interfering RNA (FOXL2-siRNA) treatment resulted in enhanced cleaved-Caspase3 protein expression and cleaved-Caspase3/Caspase3 ratio in EC-ESCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>FOXL2 participates in the occurrence and development of EM through promoting epithelial-mesenchymal transition procession and enhancing the migration and invasion of EC-ESCs, suggesting that FOXL2 may be a new therapeutic target for the EM therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942760","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}
Humblenoble Stembridge Ayuk, Susanne Arnold, Arkadiusz Pierzchalski, Mario Bauer, Violeta Stojanovska, Ana Claudia Zenclussen
{"title":"SARS-CoV-2 Activated Peripheral Blood Mononuclear Cells (PBMCs) Do Not Provoke Adverse Effects in Trophoblast Spheroids","authors":"Humblenoble Stembridge Ayuk, Susanne Arnold, Arkadiusz Pierzchalski, Mario Bauer, Violeta Stojanovska, Ana Claudia Zenclussen","doi":"10.1111/aji.70039","DOIUrl":"10.1111/aji.70039","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Although it is still uncertain whether Severe Acute Respiratory Coronavirus (SARS-CoV-2) placental infection and vertical transmission occur, inflammation during early pregnancy can have devastating consequences for gestation itself and the growing fetus. If and how SARS-CoV-2-specific immune cells negatively affect placenta functionality is still unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of study</h3>\u0000 \u0000 <p>We stimulated peripheral blood mononuclear cells (PBMCs) from women of reproductive age with SARS-CoV-2 peptides and cocultured them with trophoblast spheroids (HTR-8/SVneo and JEG-3) to dissect if SARS-CoV-2-activated immune cells can interfere with trophoblast functionality. The activation and cytokine profile of the PBMCs were determined using multicolor flow cytometry. The functionality of trophoblast spheroids was assessed using microscopy, enzyme-linked immunosorbent assay (ELISA), and RT-qPCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SARS-CoV-2 S and M peptides significantly activated PBMCs (monocytes, NK cells, and T cells with memory subsets) and induced the upregulation of proinflammatory cytokines, such as IFNγ. The activated PBMCs did not impact the viability, growth rate, and invasion capabilities of trophoblast spheroids. Furthermore, the hormonal production of hCG by JEG-3 spheroids was not compromised upon coculture with the activated PBMCs. mRNA transcript levels of genes involved in trophoblast spheroid functional pathways were also not dysregulated after coculture.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Together, the findings of our in vitro coculture model, although not fully representative of in vivo conditions, strongly support the claim that the interaction of SARS-CoV-2-activated peripheral blood immune cells with trophoblast cells at the fetal–maternal interface does not negatively affect trophoblast functionality. This goes in hand with the recommendation of vaccinating pregnant women in their first trimester.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942761","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}