American Journal of Reproductive Immunology最新文献

{"title":"Effects of Common Therapies for Threatened Preterm Labor on the Placental Inflammatory Response.","authors":"Jessica Weng, Francisco Cortina, Suyun Ling, Sylvie Girard","doi":"10.1111/aji.70316","DOIUrl":"10.1111/aji.70316","url":null,"abstract":"<p><strong>Problem: </strong>Patients with threatened preterm labor (PTL) are treated with antibiotics, corticosteroids, and magnesium sulfate to mitigate infection, promote fetal lung maturation, provide fetal neuroprotection and overall minimize the impact of prematurity on the neonate. However, the effect of these drugs on the placental inflammatory profile is unknown even though these are given systemically and reach the placenta. We evaluated their action in an ex vivo model of placental inflammation.</p><p><strong>Method of study: </strong>Placental explants from uncomplicated pregnancies were exposed to lipopolysaccharide (LPS) ± azithromycin, betamethasone, and/or magnesium sulfate. Production (lysate) and secretion (supernatant) of pro- and anti-inflammatory cytokines were assessed by ELISA.</p><p><strong>Results: </strong>Both pro- and anti-inflammatory cytokines were increased by LPS versus untreated. Azithromycin, or magnesium sulfate did not alter the inflammatory profile by themselves nor when added at the same time or 24 h after LPS. Betamethasone decreased both pro- and anti-inflammatory cytokines only when administered at the same time as LPS, without any effects if delayed.</p><p><strong>Conclusions: </strong>Therapeutic interventions classically used for preterm labor (PTL) do not impact the placental inflammatory profile by themselves or in the context of an ex vivo placental explants model of LPS-induced inflammation, except for betamethasone when administered concurrently with LPS.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 3","pages":"e70316"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863477","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":"Feto-Maternal Microchimerism and the Brain: Mechanisms, Neurological Implications, and Translational Perspectives.","authors":"Nosarieme O Abey","doi":"10.1111/aji.70317","DOIUrl":"10.1111/aji.70317","url":null,"abstract":"<p><strong>Problem: </strong>Microchimerism in the brain is a common phenomenon, where in cells cross between mother and fetus during pregnancy, and persist for decades. It has been studied primarily within reproductive immunology and transplantation medicine. The relevance of microchimerism to central nervous system biology, neurological disease, and experimental chimeric modelling has received comparatively little systematic attention. This review sought evidence across the biology of feto-maternal microchimerism, its association with neurological disease, and the emerging field of experimental chimeric brain modelling, to extrapolate a cohesive mechanistic framework.</p><p><strong>Method: </strong>Research articles in reproductive immunology, neurodevelopment, and neurodegeneration were gathered to assess the potential roles of fetal microchimeric cells (FMc) in brain health and disease. By combining natural microchimerism with experimental chimeric models, a framework for understanding how nonself cells influence the maternal brain was extrapolated and critical mechanisms identified. Searches were conducted across PubMed/MEDLINE, Scopus, and Google Scholar using a dual-concept Boolean.</p><p><strong>Results: </strong>The literature reviews show that microchimeric cells cross the blood-brain barrier (BBB), adopt neural and glial phenotypes in the maternal brain parenchyma, and exhibit injury-responsive recruitment in preclinical models. Reciprocally, maternal microchimeric cells (MMc) are present in the offspring brain, where they have been found adopting neural and immune-lineage phenotypes in experimental models. These findings raise the possibility that bidirectional microchimerism influences susceptibility to neurological disease, modulates neuroimmune signaling, and contributes to endogenous repair, although causal mechanisms remain unresolved. Experimental chimeric brain models have extended these principles into therapeutic contexts. Establishing the functional mechanism and directionality requires more prospective longitudinal cohort studies and transcriptional profiling at single-cell resolution in microchimeric brain-resident populations.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 3","pages":"e70317"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863545","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":"Immunomodulatory Effects of Tokishakuyakusan on Progesterone Withdrawal-Induced Uterine Inflammation in Pregnant Mice.","authors":"Takeshi Nagamatsu, Manami Yanagisawa, Yohei Tokita, Keisuke Nakajima, Tomohiro Otani, Ayumi Taguchi, Mari Ichinose, Keiich Kumasawa, Takayuki Iriyama","doi":"10.1111/aji.70318","DOIUrl":"10.1111/aji.70318","url":null,"abstract":"<p><strong>Problem: </strong>Tokishakuyakusan (TSS) is a traditional Japanese Kampo medicine widely used to support pregnancy; however, its molecular mechanisms remain poorly understood. This study aimed to elucidate the progesterone-related immunomodulatory mechanisms underlying the pregnancy-supportive effects of TSS using a mouse model of progesterone withdrawal induced by mifepristone.</p><p><strong>Methods: </strong>Pregnant mice were fed either a control diet or a diet containing 1% TSS from mating until late gestation. On day 15 postcoitus, all mice received low-dose mifepristone to induce functional progesterone withdrawal. Cytokine and chemokine profiles in serum, corpus uteri, and placenta were analyzed using multiplex assays, and uterine expression of progesterone-responsive and inflammatory genes were evaluated by real-time RT-PCR.</p><p><strong>Results: </strong>Mifepristone administration induced a systemic proinflammatory response, characterized by increased serum levels of G-CSF, IL-6, KC, and MCP-1. TSS administration increased G-CSF without affecting fetal number, fetal weight, or placental weight. In the corpus uteri, TSS significantly suppressed IL-6 protein expression, whereas placental cytokine profiles were largely unaffected. Furthermore, TSS significantly increased uterine mRNA expression of the progesterone-responsive anti-inflammatory molecules secretory leukocyte peptidase inhibitor (SLPI) and progranulin (PGRN).</p><p><strong>Conclusions: </strong>These findings suggest that TSS mitigates inflammation associated with progesterone withdrawal by suppressing uterine IL-6 and increasing the expression of progesterone-responsive anti-inflammatory molecules such as SLPI and PGRN. These findings suggest that TSS may modulate progesterone-responsive anti-inflammatory pathways through increased expression of SLPI and PGRN while suppressing uterine IL-6.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 3","pages":"e70318"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890715","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":"Correction to \"Interleukin-6 Downregulates T Helper 17 Cytokines via Indoleamine 2,3-Dioxygenase 1 at the Maternal-Fetal Interface\"","authors":"","doi":"10.1111/aji.70304","DOIUrl":"https://doi.org/10.1111/aji.70304","url":null,"abstract":"<p>X. Tang, S. Dao, J. Luo, et al., “Interleukin-6 Downregulates T Helper 17 Cytokines via Indoleamine 2,3-Dioxygenase 1 at the Maternal-Fetal Interface,” <i>American Journal of Reproductive Immunology</i> 96, no. 1 (2026): e70289, https://doi.org/10.1111/aji.70289.</p><p>Description of error</p><p>We apologize for these errors.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148856698","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":"Placental Extracellular Vesicles in Preeclampsia: Molecular Cargo, Pathophysiological Roles, and Emerging Diagnostic and Therapeutic Frontiers","authors":"Marhaen Hardjo,&nbsp;Alfi Sophian","doi":"10.1111/aji.70315","DOIUrl":"https://doi.org/10.1111/aji.70315","url":null,"abstract":"<div>\u0000 \u0000 <p>Preeclampsia (PE) affects 2%–8% of pregnancies globally and remains a leading cause of maternal and perinatal mortality. A central clinical gap is the absence of analytically and clinically validated non-invasive biomarkers capable of predicting PE before symptom onset. Current clinical tools, including angiogenic markers (sFlt-1/PlGF ratio) and first-trimester risk algorithms, have limitations that underscore the need for complementary approaches. Placental extracellular vesicles (EVs)—small particles released predominantly by syncytiotrophoblast cells—are implicated across PE pathophysiology. Circulating total small EV (sEV) concentrations, typically 30–150 nm and isolated by differential centrifugation or size-exclusion chromatography, are measurably elevated in maternal circulation from the first trimester in women who develop PE; this operational, size- and isolation-based definition does not by itself establish placental origin, which requires placental-attribution markers (e.g., PLAP, syncytins) discussed in Section 2. Their molecular cargo, encompassing microRNAs (miR-210, miR-15a-5p, miR-520a-5p, miR-146a-5p, miR-93-5p), anti-angiogenic proteins (sFlt-1, sEng), and hypoxia markers (HIF-1α), reflects placental pathophysiology. Recent evidence has expanded the known pathophysiological reach of placental EVs: beyond endothelial dysfunction and angiogenic imbalance, they are now implicated in blood-brain barrier disruption via claudin-5 (CLDN5) downregulation, supporting a plausible mechanistic link to neurological complications of PE. Proteomic profiling of EV fractions identifies molecularly distinct PE subtypes, enabling investigational subtype discrimination beyond current clinical criteria. Recent in vivo proof-of-concept evidence in a rat model demonstrates that amniotic fluid-derived EV-associated miR-146a-5p ameliorates PE phenotypes, opening a preclinical therapeutic avenue. This narrative review synthesises evidence from a structured PubMed/MEDLINE and Scopus search covering 2017–March 2025 on placental EV biogenesis, cargo heterogeneity, immune modulation, organ-specific pathological consequences, and translational potential as first-trimester liquid biopsy candidates. Methodological standardization challenges and future research priorities are discussed.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148856697","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":"Impact of Gestational Maternal SARS-CoV-2 Infection on Neonatal Inflammatory Biomarkers","authors":"Bushra Amreen,&nbsp;Floriana Milazzo,&nbsp;Frederieke Gigase,&nbsp;Darwin D'souza,&nbsp;Natalie Samper,&nbsp;Joseph Thomas Martin,&nbsp;Seunghee Kim-Schulze,&nbsp;Whitney Lieb,&nbsp;Lot D. de Witte,&nbsp;Veerle Bergink,&nbsp;Jia Chen,&nbsp;Corina Lesseur,&nbsp;Anna-Sophie Rommel","doi":"10.1111/aji.70313","DOIUrl":"10.1111/aji.70313","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Since the beginning of the pandemic, millions of pregnant women have been exposed to SARS-CoV-2, eliciting concerns about maternal and fetal sequelae. Yet, the impact of SARS-CoV-2 on the child's immune response remains largely unexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Herein, we leverage 833 mother-infant dyads from a New York City-based pregnancy cohort to explore prospective associations between maternal gestational SARS-CoV-2 infection and inflammatory biomarkers in newborns. Of the mothers, 100 were infected with SARS-CoV-2 during pregnancy, as confirmed through self-report, antibody and/or PCR test results. We obtained 92 inflammatory biomarker levels in neonatal dried blood spots (DBS) using the Olink Target 96 Inflammation panel. An empirical Bayes method was used to fit linear regression models to assess the effects of maternal infection during pregnancy on neonatal inflammatory markers at birth. We also conducted stratified analyses by timing of infection in early (&lt;20 weeks) versus late (≥20 weeks) gestation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Higher levels of 22 inflammatory biomarkers, including CD5, TNFSF14, CD8a, TGF-α, and CD244, were observed in neonates prenatally exposed to SARS-CoV-2 compared to unexposed neonates (<i>p_adj</i> &lt; 0.05). Early-gestation infection was associated with increased levels of eight inflammatory biomarkers, including TNFSF14, TGF-α and decreased IL-18 levels, while late-gestation infection was linked to elevations in 12 biomarkers, including CD5, CD6, PD-L1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results indicate that maternal SARS-CoV-2 infection during pregnancy influences inflammatory biomarkers in newborns, with the timing of infection playing a critical role in determining these immune profiles. Thus, this study emphasizes the need for further research and long-term follow-up to examine future health consequences for the child.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811783","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":"Therapeutic Interventions for Preeclampsia: Integrating Placental and Maternal Perspectives","authors":"Shrreya S. Sudade,&nbsp;Luisa Wallentowitz,&nbsp;Emma M. Giesen,&nbsp;Evelyn A. Huhn,&nbsp;Ann-Christin Tallarek,&nbsp;Sandra M. Blois,&nbsp;Stefan Verlohren","doi":"10.1111/aji.70299","DOIUrl":"10.1111/aji.70299","url":null,"abstract":"<div>\u0000 \u0000 <p>Preeclampsia (PE), a hypertensive disorder of pregnancy, is one of the leading causes of maternal and fetal mortality worldwide. Beyond the immediate pregnancy impact, it is also associated with increased long-term risks in both the mother and the offspring. Currently, no causal therapy exists. Consequently, the complex and heterogeneous nature of PE necessitates the exploration of novel therapeutic targets to improve maternal and fetal outcomes. This review summarizes models of pathogenesis in PE, particularly the two-stage model of the development of PE, where the placenta is suggested to be the main source of the disease, and the postulation that PE is a result of dysfunction of the maternal cardiovascular system. We explore novel therapeutic approaches, considering the underlying mechanisms such as galectin-13, placental growth factor, therapeutic plasma exchange (TPE), trophoblast-targeted nanomedicine, gene therapy, nitric oxide donors, endothelin receptor antagonists, and mesenchymal stem cells. Challenges in translating preclinical findings to clinical practice, including animal model limitations and ethical considerations, are discussed. Finally, this review integrates current treatment options, discusses their limitations, highlights ethical considerations, and outlines future directions for PE therapeutics, emphasizing the need for personalized therapeutic strategies.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811774","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":"Evaluation of Systemic Inflammatory Indices in Pregnant Women With Deep Vein Thrombosis","authors":"Dilara Sarikaya Kurt,&nbsp;Recep Taha Ağaoğlu,&nbsp;Ayberk Çakır,&nbsp;Ahmet Kurt,&nbsp;Aziz Kından,&nbsp;Özgür Volkan Akbulut,&nbsp;Murat Levent Dereli,&nbsp;Yaprak Engin Üstün","doi":"10.1111/aji.70298","DOIUrl":"https://doi.org/10.1111/aji.70298","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Venous thromboembolism (VTE) remains an important cause of maternal morbidity and mortality, yet the diagnosis of deep vein thrombosis (DVT) during pregnancy is challenging because clinical symptoms overlap with physiological gestational changes and D-dimer specificity is reduced. This study evaluated the association between complete blood count-derived systemic inflammatory indices and pregnancy-associated DVT.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This retrospective case-control study included 36 pregnant women with Doppler ultrasonography-confirmed DVT and 36 healthy pregnant controls matched for maternal age and gestational age. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) were calculated from routine complete blood counts. Univariable and multivariable Firth penalized logistic regression analyses were performed, adjusting for body mass index, history of cesarean delivery, and varicose veins. Elastic net penalized regression was used for variable selection. Gestational age-stratified sensitivity analyses, false discovery rate correction, receiver operating characteristic (ROC) analyses, and a supplementary trimester-specific D-dimer threshold analysis were also performed.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Women with DVT had higher NLR, SII, SIRI, AISI, and D-dimer levels than controls, whereas PLR and MLR did not differ significantly. After false discovery rate correction, NLR, SII, SIRI, and AISI remained statistically significant. In multivariable Firth regression, NLR, SII, and D-dimer were independently associated with DVT. Elastic net analysis identified NLR and SII as the most informative inflammatory indices. ROC analyses showed moderate discriminatory performance for NLR and SII, either alone or combined with D-dimer. The gestational age-stratified analyses showed a consistent direction of association, while trimester-specific D-dimer thresholds increased specificity but substantially reduced sensitivity in this cohort.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;NLR and SII were associated with pregnancy-associated DVT and may reflect the thrombo-inflammatory component of this condition. However, the findings are exploratory and hypothesis-generating. These indices should be considered only as adjunctive markers within the existing diagnostic workflow, not as standalone diagnostic tools. Prospective studies using standardized sampling and pregnancy-adapte","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783930","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":"Menstruation is Associated With Cyclical Granulysin Peaks in Vaginal Secretions Despite Stable Expression by Cervicovaginal Immune Cells","authors":"Sean M. Hughes,&nbsp;Claire N. Levy,&nbsp;Dendron R. Chamberlain,&nbsp;Dana Varon,&nbsp;Britt Murphy,&nbsp;Katharine Schwedhelm,&nbsp;Juma Shafi,&nbsp;Jennifer M. Lund,&nbsp;Martin Prlic,&nbsp;Stephen C. De Rosa,&nbsp;Elizabeth Micks,&nbsp;Christine Johnston,&nbsp;Florian Hladik","doi":"10.1111/aji.70311","DOIUrl":"https://doi.org/10.1111/aji.70311","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>The anti-microbial protein granulysin is present in vaginal secretions during the follicular phase of the menstrual cycle but nearly disappears during the luteal phase. The reason for this change is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants (<i>n</i> = 23) with regular menstrual cycles collected daily vaginal swabs for granulysin ELISAs. Endocervical cytobrushes, ectocervical biopsies, vaginal biopsies, and PBMC were collected across the cycle to enumerate granulysin-expressing cells by flow cytometry. Cycle phase was determined by daily urinary luteinizing hormone testing and confirmed by serum progesterone levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Granulysin levels in secretions were up to 10 000 times higher during menstruation than during the luteal phase (menstruation, median 3924 pg/mL [IQR 400–17,280]; luteal, median and IQR undetectable [&lt;7.81 pg/mL]). In the endocervical canal, granulysin-expressing cells were much more abundant during menstruation than during the mid-follicular or mid-luteal phases. In contrast, the number of granulysin-expressing cells in the ectocervix and vagina remained stable during the cycle. The most abundant granulysin-expressing cell types in the mucosa were CD8 T cells and NK cells. In a minority of participants, granulysin was consistently detected in luteal-phase swabs; this phenomenon was associated with parity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Granulysin in vaginal secretions is associated with menstruation and concomitant with a spike in granulysin-expressing cells in the endocervical canal. This result explains the much higher granulysin levels in secretions during the follicular than the luteal phase. In contrast, immune cells from ectocervical and vaginal biopsies express granulysin independently of the menstrual cycle, indicating their continuous ability to respond to microbial infection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784424","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 Impact of the Vaginal Microbiome and Microbial Metabolites on HIV Transmission at the Female Reproductive Tract Epithelial Barrier","authors":"Brianna Jesaveluk,&nbsp;Paula Ellenberg,&nbsp;Anna C. Hearps,&nbsp;Gilda Tachedjian","doi":"10.1111/aji.70312","DOIUrl":"https://doi.org/10.1111/aji.70312","url":null,"abstract":"<p>Despite major advances in biomedical HIV prevention strategies, almost 50% of the 1.3 million new HIV infections in 2024 occurred in women and girls through heterosexual transmission. Choice in HIV prevention modalities is needed throughout a women's lifespan to increase pre-exposure prophylaxis uptake; however, there is a paucity of topical, on-demand options. To establish HIV infection, the virus translocates across the epithelial barrier of the upper and lower female reproductive tract to infect CD4 + HIV target cells in the submucosa. The vaginal microbiome modulates this process. Women colonised with an optimal <i>Lactobacillus</i>-dominated vaginal microbiota are more protected against acquiring HIV compared to women with a non-optimal vaginal microbiota including bacterial vaginosis (BV), characterised by an overgrowth of diverse anaerobes and a paucity of beneficial lactobacilli. Optimal <i>Lactobacillus</i> spp. produce ∼1% lactic acid, which in women with a <i>Lactobacillus</i>-dominant microbiota acidifies the vaginal pH to less than 4.5, inactivates HIV, exerts antimicrobial effects against BV–associated bacteria, directly inhibits inflammatory responses elicited from cervicovaginal epithelial cells and blocks HIV translocation in vitro. Beneficial properties of optimal vaginal lactobacilli and/or lactic acid can potentially be exploited in vaginal delivery strategies to help prevent vaginal dysbiosis and its adverse sexual and reproductive outcomes including HIV.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"96 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70312","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783993","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}