American Journal of Reproductive Immunology最新文献

{"title":"NK Cell Profiling: Expression of TIGIT and LAG3 as Immune Checkpoints in Advanced Endometriosis","authors":"Mohammad Abbaszadeh,&nbsp;Mohammadreza Karimi,&nbsp;Ashraf Moini,&nbsp;Reyhaneh Hosseini,&nbsp;Samira Mirzaei,&nbsp;Lida Garrosi,&nbsp;Samira Rajaei","doi":"10.1111/aji.70270","DOIUrl":"10.1111/aji.70270","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Endometriosis (EMS) is a gynecological condition that is associated with chronic pelvic pain and inflammation. Evidence supports the idea that natural killer (NK) cell dysfunction contributes to EMS pathogenesis; nevertheless, the role of T cell immunoreceptors with Ig and ITIM domains (TIGIT) and lymphocyte activation gene 3 (LAG3) in the development of endometriosis-associated immunological abnormalities is not yet reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>The present study used multicolor flow cytometry to compare the frequency of NK cells expressing TIGIT and LAG3 in the peripheral blood (PB) and peritoneal fluid (PF) of women with and without endometriosis. The levels of soluble form of LAG3 (sLAG3) were compared between EMS and non-EMS participants in both PB and PF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The number of NK cells expressing TIGIT increased in the PF of EMS compared to the other benign gynecological conditions (OBGC) (Pv = 0.0089); however, this difference was not statistically significant in PB. In contrast, an increased frequency of LAG3+NK cells was detected in both PF and PB in EMS compared to the controls. Additionally, a higher level of sLAG3 was stated in both the PB and PF of EMS patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>An impaired number of TIGIT+ and LAG3+NK cells was detected in the peritoneal microenvironment of EMS, which may be responsible for impaired immune surveillance, promoting the survival of ectopic lesions, and contributing to the evolution of EMS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248781","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":"Effect of Tacrolimus on Pregnancy Outcomes in Patients with Repeated Implantation Failure (RIF) and Elevated Th1/Th2 Ratio: A Randomized, Double-Blind, Placebo-Controlled Trial","authors":"Sepideh Peivandi,&nbsp;Marzieh Zamaniyan,&nbsp;Maedeh Etghani,&nbsp;Mohammad Malekan,&nbsp;Saeid Taghiloo,&nbsp;Hossein Asgarian-Omran","doi":"10.1111/aji.70268","DOIUrl":"10.1111/aji.70268","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Repeated implantation failure (RIF) is often linked to immune dysregulation, particularly an elevated Th1/Th2 ratio that impairs embryo implantation. While several immunotherapies have been used, their efficacy and safety remain unclear. This study evaluated the clinical efficacy and immunomodulatory effects of tacrolimus treatment in women with RIF exhibiting elevated Th1/Th2 ratios.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a randomized, double‑blind, placebo‑controlled trial conducted between April 2024 to May 2025. A total of 153 RIF patients were screened, and 91 patients with a Th1/Th2 ratio ≥10.3 were identified. After exclusions, 80 patients were randomized 1:1 to tacrolimus or placebo. Patients were administered tacrolimus or placebo for 16 days, beginning 2 days before embryo transfer and continuing until the pregnancy test day. The primary outcome was the clinical pregnancy rate. Live birth was prespecified as the key secondary outcome. Additional secondary outcomes included miscarriage, ongoing pregnancy, multiple gestation, changes in the Th1/Th2 ratio, and adverse events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Clinical pregnancy occurred in 17 of 40 patients (42.5%) in the tacrolimus group compared with 6 of 40 patients (15.0%) in the placebo group (RR = 2.83, 95% CI: 1.30–6.44; <i>p =</i> 0.0125), corresponding to an absolute risk difference of 27.5% and a number needed to treat (NNT) of 4. Live birth occurred in 11 of 40 patients (27.5%) versus 3 of 40 patients (7.5%), respectively (RR = 3.67, 95% CI: 1.21–11.63; <i>p =</i> 0.0367), with an absolute risk difference of 20.0% and an NNT of 5. The Th1/Th2 ratio decreased significantly after treatment in the tacrolimus group (17.01 ± 3.99 to 12.56 ± 2.78, <i>p &lt;</i> 0.0001), whereas no significant change was observed in the placebo group. No severe adverse events or treatment discontinuations occurred.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Tacrolimus treatment improved clinical pregnancy outcomes and effectively reduced elevated Th1-dominant immune responses in RIF patients. These findings support the use of tacrolimus as an immunosuppressive therapy for RIF patients with elevated Th1/Th2 ratios.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>This trial was registered with the Iranian Registry of Clinical Trials (IRCT20231127060207N1).</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148196965","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":"Pyroptosis in Ovarian Aging, and Its Influence on Female Reproductive Health in Aged Ovaries","authors":"Caglar Berkel","doi":"10.1111/aji.70265","DOIUrl":"10.1111/aji.70265","url":null,"abstract":"<div>\u0000 \u0000 <p>Pyroptosis is a lytic cell death mechanism mediated by the gasdermin family of proteins, resulting in the release of certain pro-inflammatory molecules to the extracellular space. Ovaries serve as the source of oocytes and main producer of steroid sex hormones, making them essential with respect to the maintenance of fertility and endocrine homeostasis during reproductive lifespan in females. Ovaries exhibit early-onset aging-associated dysfunction, compared to most other tissues, with dramatic functional declines after only 30 years of age in women. In this review, I covered studies reporting the age-dependent changes in pyroptotic cell death in ovaries, and the effects of increased pyroptotic events in aged ovaries on the female reproductive health. Increased pyroptosis of diverse cell types in the ovarian microenvironment might adversely influence ovarian function and composition in the course of ovarian aging, mostly by its effects on inflammation and cellular senescence. Novel strategies targeting pyroptotic cell death in aging ovaries might alleviate certain adverse outcomes in terms of fertility or female reproductive health in general. Considering that many molecules which are known to inhibit pyroptosis are currently available, a better molecular understanding and evaluation of these pyroptosis inhibitors in the clinic for the mitigation of aging-associated declines in ovarian function and female fertility is needed.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155073","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":"T-Cell Biology in the Female Reproductive Tract: Relevance to HIV Infection","authors":"Barbara L. Shacklett,&nbsp;Ramatoulaye H. Ouattara,&nbsp;April L. Ferre","doi":"10.1111/aji.70259","DOIUrl":"10.1111/aji.70259","url":null,"abstract":"<p>Worldwide, most HIV infections occur across a mucosal surface during sexual contact, with women accounting for nearly half of reported new HIV infections across the globe in 2024. Most new infections in women and girls are believed to involve transmission across mucosal surfaces of the lower reproductive tract, which includes the vagina and ectocervix. Nevertheless, HIV-susceptible target cells are present in both the lower and upper reproductive tract, as are antigen-specific T-cells. Advances in the field of T-cell biology over the past decades have elucidated the differentiation and trafficking of mucosal T-cells, including tissue-resident populations. In addition, recent studies incorporating advances in tissue sampling, immune cell phenotyping and multi-omics technologies have enhanced our understanding of adaptive immune responses to HIV within the reproductive tract. This review summarizes our current understanding of T-cell biology in the female reproductive tract and its relevance to HIV infection.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70259","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136287","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":"Novel Hematological Inflammatory Indices in Early Pregnancy: The Predictive Value of the Cumulative Inflammatory Index and Mean Corpuscular Volume/Lymphocyte for Gestational Diabetes Mellitus","authors":"Deniz OLUKLU,&nbsp;Fatma OLUKLU,&nbsp;Selma SUREN,&nbsp;Aysegül GENCER,&nbsp;Taylan ONAT","doi":"10.1111/aji.70264","DOIUrl":"10.1111/aji.70264","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate the predictive value of first and second trimester hematological inflammatory indices—including the novel cumulative inflammatory index (IIC) and mean corpuscular volume-to-lymphocyte ratio (MCVL)—for the subsequent development of gestational diabetes mellitus (GDM). Additionally, the study will assess whether these markers differ between GDM subgroups managed with diet alone versus insulin therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This case-control study enrolled 150 pregnant women, with 75 diagnosed with GDM and 75 serving as healthy controls. Hematological inflammatory indices—namely, NLR, MLR, PLR, dNLR, AISI, SII, SIRI, IIC, and MCVL—were calculated from first- and second-trimester complete blood count parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>First-trimester inflammatory indices (NLR, MLR, PLR, dNLR, AISI, SII, SIRI, IIC, and MCVL) were significantly elevated in the GDM group compared to controls (all <i>p</i> &lt; 0.05). NLR demonstrated the highest discriminative accuracy (AUC 0.782; 95% CI: 0.709–0.855), followed by SIRI (AUC 0.778) and IIC (AUC 0.775). Among GDM patients, 22 (29.3%) required insulin therapy. Insulin-treated patients exhibited significantly higher SIRI_1 than diet-managed patients (<i>p</i> = 0.025), and showed a substantially elevated inflammatory burden across multiple second-trimester indices. First-trimester fasting glucose was positively correlated with several second-trimester inflammatory indices, including AISI_1 (<i>r</i> = 0.351, <i>p</i> = 0.002) and SII_2 (<i>r</i> = 0.342, <i>p</i> = 0.003).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>First-trimester hematological inflammatory indices, including the novel IIC and MCVL, are associated with subsequent development of GDM. Furthermore, these indices offer moderate predictive accuracy when derived from routine antenatal blood tests. The clinical usefulness of these findings necessitates prospective validation in larger, multicenter cohorts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136160","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 in the Female Reproductive Tract","authors":"Sean M. Hughes,&nbsp;Lisa M. Frenkel","doi":"10.1111/aji.70262","DOIUrl":"10.1111/aji.70262","url":null,"abstract":"<p>Antiretrovirals can prevent the spread of replicating HIV within the host and decrease the virus in plasma to levels undetectable in clinical assays, and in genital secretions to untransmissible levels. However, during effective treatment with antiretrovirals, infectious HIV persists lifelong because the virus integrates into the host's DNA, and these proviruses are replicated within the host's DNA when the infected host cells proliferate. Cells with infectious virus that persist during antiretroviral therapy (ART), the HIV reservoir, are spread throughout the body, including the female reproductive tract (FRT). HIV-infected cells have been detected at multiple sites in the FRT, and the virus is shed in FRT secretions; however, less is known about the FRT reservoir than about other sites in the body. The FRT consists of the ovaries, fallopian tubes, uterus, cervix, and vagina. This collection of diverse tissues has several unique features: squamous and columnar epithelia, hormone production and regulation, cyclical changes, a unique microbiome, and exposure to sexual activity. Given these unique features, it cannot be assumed that infected cells located in the FRT will respond to curative therapeutic interventions in the same manner as infected cells elsewhere in the body. Thus, it is imperative to increase our understanding of the features of the HIV reservoir in the FRT. Here, we review data on the viral reservoir and shedding in the FRT and relate it to strategies to cure HIV infection.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148051915","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":"The Spatial Biology of HIV Transmission and Infection: Imaging the Female and Male Reproductive Tracts","authors":"Ann M. Carias,&nbsp;Claudia C. Stroupe,&nbsp;Thatiane Russo,&nbsp;Thomas J. Hope","doi":"10.1111/aji.70261","DOIUrl":"10.1111/aji.70261","url":null,"abstract":"<p>HIV transmission through the female and male reproductive tracts is governed by spatially organized interactions between virions, epithelial barriers, and tissue-resident immune cells. Imaging approaches have been central to defining these earliest events, progressing from classical histology and immunohistochemistry (IHC) to modern fluorescence, multiphoton microscopy, tissue clearing, and spatially resolved molecular platforms. Early FFPE-based IHC and ISH established foundational maps of infected cells within intact mucosa, revealing regional immune heterogeneity and linking susceptibility to barrier integrity and target-cell density. Fluorescent virion imaging extended these findings by visualizing viral movement across mucosal surfaces and the first contacts with permissive cells. In parallel, non-human primate (NHP) models enabled temporal resolution of initial SIV infection foci and dissemination patterns under controlled exposure conditions. More recent techniques, including RNAscope and DNAscope, light-sheet microscopy, multiplex fluorescence, and PET/CT, allow quantitative mapping of viral nucleic acids, reservoir populations, and immune microenvironments across whole tissues and organs. Together, these spatial imaging platforms have demonstrated that HIV establishes infection within discrete mucosal niches that vary by anatomical site and immune architecture. Integrated imaging increasingly reveals how HIV behaves within the distinct mucosal environments of the female and male reproductive tracts.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70261","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148051947","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":"Causal Effects of Gut Microbial Genera on Abnormal Spermatozoa Revealed Through Integrated Mendelian Randomization and Mediation Analysis","authors":"Huixiang Yang,&nbsp;Jing Gao","doi":"10.1111/aji.70263","DOIUrl":"10.1111/aji.70263","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Sperm quality is a key contributing factor in infertility. This study aimed to investigate the causal relationship between gut microbiota genera and abnormal spermatozoa (defects in sperm count, motility, or morphology) and to evaluate potential mediating factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and methods</h3>\u0000 \u0000 <p>Summary statistics for gut microbiota genera, abnormal spermatozoa, microbiota metabolic pathways, immune cell traits, and serum bioavailable testosterone (BioT) levels were extracted from publicly available GWAS databases. A fixed-effects meta-analysis was performed on gut microbiota genera from the MiBioGen and DMP cohorts, followed by two-sample Mendelian randomization (MR) analysis to evaluate causal associations. To strengthen reliability, a triangulation framework incorporating MR analyses, HyPrColoc colocalization analysis, and Steiger directionality tests was employed. Mediation analysis focused on microbiota metabolic pathways, immune cell traits, and BioT levels as potential mediators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eight gut microbiota genera showed significant causal associations with abnormal spermatozoa: four risk genera (<i>Lachnospiraceae UCG001.id.11321, Coprococcus 1.id.11301, Barnesiella, Dorea</i>) and four protective genera (<i>Clostridium sensu stricto 1.id.1873, Ruminiclostridium 6.id.11356</i>, <i>Lachnospiraceae_noname, Veillonella</i>). The triangulation framework validated these causal relationships. Although two genera affected BioT levels, formal mediation analysis did not confirm BioT, immune cells, or metabolic pathways as mediators, suggesting novel gut-testis axis mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This large-scale MR analysis establishes a causal connection between specific gut microbiota genera and abnormal spermatozoa. The “causation without colocalization” pattern and null mediation findings suggest distant regulatory mechanisms and novel gut-testis axes, offering microbiota-targeted therapeutic strategies for male infertility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148051937","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148096066","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 S1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148086735","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}