American Journal of Reproductive Immunology最新文献

{"title":"Elevated Aspartate Aminotransferase to Platelet Ratio Index Associated With Dyslipidaemia and Obesity in Patients With Polycystic Ovary Syndrome.","authors":"Muradiye Yildirim, Neval Cayonu Kahraman, Mesut Simsek, Onur Numan, Belgin Savran Ucok, Dilara Duygulu Bulan, Yaprak Engin-Ustun","doi":"10.1111/aji.70171","DOIUrl":"https://doi.org/10.1111/aji.70171","url":null,"abstract":"<p><strong>Problem: </strong>Polycystic ovary syndrome (PCOS) and steatotic liver disease associated with metabolic dysfunction are closely related. The aspartate aminotransferase platelet ratio index (APRI), one of the non-invasive indices, has a high prognostic value in metabolic and cardiovascular abnormalities. The primary outcome of this study was to compare APRI levels in PCOS patients with different metabolic subgroups.</p><p><strong>Method of study: </strong>The study included women aged 20-45 years with a diagnosis of PCOS. Baseline blood samples were collected after spontaneous menstrual bleeding between days 2 and 5 of the menstrual cycle, following an overnight fast. Patients were classified as obese or non-obese, with or without hypertriglyceridemia, and with normal or abnormal fasting glucose.</p><p><strong>Results: </strong>A total of 106 patients were included in the study. Triglyceride, low-density lipoprotein cholesterol levels and APRI scores of lean and overweight patients were significantly lower than those of obese patients. APRI was significantly lower in normotriglyceridemic PCOS patients. The APRI score was positively correlated with triglycerides and negatively correlated with sex-hormone binding globulin.</p><p><strong>Conclusions: </strong>Current evidence-based international guidelines emphasise that PCOS is not an isolated condition but a systemic endocrine disorder that requires multidisciplinary management. Metabolic abnormalities and indicators of cardiovascular disease risk can be assessed non-invasively in women with PCOS, one of the world's most important health problems. At the same time, patients at risk can be followed more closely and carefully. Given that metabolic risks vary by phenotype and region, personalised assessment and management are essential.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 4","pages":"e70171"},"PeriodicalIF":2.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224670","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":"Correction to \"Circ-ADAM9 Knockdown Reduces Insulin Resistance and Placental Injury in Diabetic Mice via MAPK Pathway Inactivation\"","authors":"","doi":"10.1111/aji.70169","DOIUrl":"https://doi.org/10.1111/aji.70169","url":null,"abstract":"<p>A. Zhao, Y. Yang, Y. Yang, Z. Chi, and Y. Sun, “Circ-ADAM9 Knockdown Reduces Insulin Resistance and Placental Injury in Diabetic Mice via MAPK Pathway Inactivation,” <i>American Journal of Reproductive Immunology</i> 92, no. 5 (2024): e70017, https://doi.org/10.1111/aji.70017.</p><p>In published version, the institution address “The People's Hospital of Nanjing Medical University,” is incorrect. It should be “The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University”.</p><p>We apologize for this error.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197319","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 Role of Cryptotanshinone Regulates HTR-8/SVneo Cells Activity Through the p53/STAT3 Pathway in Unexplained Recurrent Spontaneous Abortion","authors":"Lidan Lu,&nbsp;Ximei Cai,&nbsp;Yang Zhang,&nbsp;Weibo Zhao,&nbsp;Haiyan Ni,&nbsp;Liping Zhang,&nbsp;Peijuan Wang","doi":"10.1111/aji.70163","DOIUrl":"10.1111/aji.70163","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study sought to investigate the therapeutic effects and mechanisms of cryptotanshinone (CT) on unexplained recurrent spontaneous abortion (URSA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The DBA/2 male and CBA/J female mice were caged together to construct a URSA model before treatment with high and medium-low doses of CT. Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of interleukin (IL)-1 beta (β), IL-17, and IL-22 in serum in each category of mice. Hematoxylin–eosin (HE) pathology was employed to detect decidua and uterine tissues, while polymerase chain reaction (PCR) was utilized to ascertain relative expression levels of serum messenger ribonucleic acid (mRNA) of IL-17, IL-22, and IL-1β. The effects of CT on H₂O₂-induced HTR-8/SVneo cells were investigated using cell counting kit-8 (CCK-8) assays and cell migration assays, while flow cytometry was used for the detection of apoptosis. Network pharmacology was used to analyze the mechanism of CT in the treatment of URSA. The repair effects and underlying mechanisms of the tumor protein 53 (p53) inhibitor and signal and transducer of transcription 3 small interfering RNA (STAT3 siRNA) were evaluated using ELISA assays, CCK-8, cell migration assays, flow cytometry, immunofluorescence, and Western blot techniques.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Different doses of CT exerted protective effects on the uterine tissues of URSA. Also, CT could reduce levels of IL-17, IL-22, and IL-1β and their relative mRNA content in the serum of URSA mice, as well as increase the activity and migration rate of HTR-8/SVneo cells, and reduce the rate of apoptosis. Using p53 and STAT3 as mechanistic targets, we found that the p53 inhibitor, STAT3 siRNA, and CT restored the migratory activity of HTR-8/SVneo cells, reduced their apoptotic rate, and simultaneously downregulated the expression of retinoic acid receptor-related orphan receptor γt (RORγt) and vascular endothelial growth factor (VEGF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The mechanism by which CT regulated the activity of HTR-8/SVneo cells involved the inhibition of p-p53, with STAT3, RORγt, and VEGF functioning as downstream targets of the p53 pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184527","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":"A Randomised Controlled Trial on the Treatment of Recurrent Implantation Failure Women Who Failed Egg Donation Cycles Using Low-Dose GM-CSF","authors":"Fabio Scarpellini,&nbsp;Marco Sbracia,&nbsp;Daniela Marconi,&nbsp;Alice Fracassi,&nbsp;Katya Santi,&nbsp;Eugenio Desole","doi":"10.1111/aji.70162","DOIUrl":"10.1111/aji.70162","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine promoting leukocyte proliferation and trophoblast growth. Recurrent implantation failure (RIF) is the repeated failure to reach pregnancy in IVF cycles. In this randomized controlled trial, the use of low dose of GM-CSF in the treatment of RIF in egg donation cycles was tested.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods of Study</h3>\u0000 \u0000 <p>A randomized controlled trial was conducted on women with RIF after egg donation cycles. The inclusion criteria were age between 30 and 49 years old: at least three previous transfers failed with good quality blastocysts in egg donation cycles: no uterine defects. The patients were randomly subdivided into two groups: one treated with subcutaneous GM-CSF 0.3microg/kg/day from the day before embryo transfer to the b-hCG day. Since RIF patients may be at risk for miscarriage, this treatment was continued until the eighth week of gestation to avoid possible early miscarriage. The control group was treated with a subcutaneous saline solution infusion in the same way as the study group. Primary outcomes were the clinical pregnancy rate and live-birth rate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Epidemiological data of the two groups did not show statistically significant differences. The clinical pregnancy rate in the GM-CSF group was 73.5% (39/53), while in control group it was 34.6% (18/52) (<i>p</i> &lt; 0.0001), the live-birth rate was 67.9% (36/53) and 28.8% (15/52), respectively (<i>p</i> &lt; 0.0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The clinical use of GM-CSF in women who experienced implantation failure may be a useful treatment in a selected group of patients. The model of women with RIF after egg donation, at the light of our results, may be considered a valid model to study this clinical entity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifier: NCT01715974.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079076","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":"Revealing the Complexity of Immunobiological Shifts From Non-Pregnant to Pregnant State","authors":"Chelsea A. DeBolt,&nbsp;Haocheng Yu,&nbsp;Valerie Riis,&nbsp;Liqhwa Ncube,&nbsp;Amir Horowitz,&nbsp;Michal A. Elovitz","doi":"10.1111/aji.70166","DOIUrl":"10.1111/aji.70166","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Significant immunological shifts, systemically and at the maternal–fetal interface, are required for successful pregnancy. As immune perturbations are emerging as pivotal drivers of adverse maternal health, elucidating how normal pregnancy alters maternal systemic immunity is imperative.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From our prospectively enrolled cohort of Black women, peripheral blood samples were collected pre-pregnancy (V1) and in the second trimester (16–24 weeks, V2). Among those who became pregnant, 23 had available samples from both time points. RNA was extracted and subjected to bulk RNA sequencing, followed by differential gene expression analyses, immune cell-type deconvolution, and pathway enrichment analyses. Participants were stratified by pre-pregnancy obesity (body mass index ≥ 30 kg/m²) to examine its impact on pregnancy-induced immune changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Pathway analyses revealed innate immune activation and increased neutrophil-driven inflammation during pregnancy. Significant increase in neutrophils and monocytes occurred during pregnancy, whereas naïve CD8+ T-cell and B-cell subsets were significantly decreased. Pre-pregnancy obesity amplified these changes, further increasing innate populations (gamma delta T cells, neutrophils) and decreasing adaptive populations (CD8 naïve T cells, B memory cells).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>From individuals with uncomplicated pregnancies, we demonstrate dramatic immunological changes when transitioning from a non-pregnant to pregnant state. Intricate immune modulation, including changes in inflammatory mechanisms and immune cell dynamics were observed. Pre-pregnancy obesity enhances these inflammatory shifts, providing insights into potential mechanisms driving adverse pregnancy outcomes in obese women. Future studies investigating how these immunological shifts are required for optimal maternal health and/or may promote increased vulnerability to adverse pregnancy outcomes will create new opportunities to improve maternal outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079116","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":"Aberrant Expression of Gonadotropin-Releasing Hormone Receptor in Human Mast Cells Enhances the Recruitments of Trophoblasts and NK Cells","authors":"Takashi Matsuzaki,&nbsp;Hiroaki Hamaguchi,&nbsp;Ken R. Ito,&nbsp;Ryota Nakagawa,&nbsp;Hiroya Nakamura,&nbsp;Hiroaki Ito,&nbsp;Chiyuki Ueshima,&nbsp;Akihiko Yoshizawa,&nbsp;Hironori Haga,&nbsp;Tatsuki R. Kataoka","doi":"10.1111/aji.70168","DOIUrl":"10.1111/aji.70168","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Gonadotropin-releasing hormone (GnRH), primarily known for its hypothalamic role in regulating gonadotropin secretion, is also expressed in extra-hypothalamic tissues, including trophoblasts at implantation sites. We investigated the association between trophoblasts and mast cells, demonstrating their role in producing leukemia inhibitory factor (LIF) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesized an additional interaction between trophoblasts and mast cells mediated by GnRH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Immunohistochemical analysis was conducted to investigate GnRH receptor (GnRHR) expressing mast cell in endometrial and tubal tissues from both pregnant and non-pregnant conditions (2005–2018). We established a human mast cell line LAD2 with forced expression of GnRHR expression (GnRHR-expressing LAD2) via lentiviral transfection method. The cells were stimulated with or without leuprorelin (1 µM) and transcriptomic analysis and cell migration assays were conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>GnRHR is expressed in decidual mast cells during uterine pregnancy and in mast cells adjacent to or embedded in trophoblasts of tubal pregnancy. Notably, GnRHR expression was also observed in endometrial mast cells in non-pregnancy conditions. The levels of transcripts encoding LIF, MMP-9, and a natural killer (NK) cell attractant C-X-C motif chemokine ligand 16 (CXCL16) were significantly upregulated in GnRHR-expressing LAD2 than in control cells. In addition, culture supernatants from GnRHR-expressing LAD2 cells enhanced the migration of the trophoblast cell line HTR-8/SVneo and the NK cell line NK-92 MI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest that GnRHR expression in mast cells promotes their supportive role in pregnancy establishment by increasing the LIF, MMP-9, and CXCL16 productions, recruiting trophoblasts and NK cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084582","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":"Comment on “Deciphering the Molecular Crosstalk of Endoplasmic Reticulum Stress and Immune Infiltration in Endometriosis”","authors":"Saraswati Sah,&nbsp;Renu Sah","doi":"10.1111/aji.70158","DOIUrl":"https://doi.org/10.1111/aji.70158","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062487","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":"Endothelial Activation and Stress Index as a Novel Prognostic Marker in Intrahepatic Cholestasis of Pregnancy: A Case–Control Study","authors":"Dilara Duygulu Bulan,&nbsp;Ruken Dayanan,&nbsp;Merve Ayas Özkan,&nbsp;Zeynep Şeyhanlı,&nbsp;Gülşan Karabay,&nbsp;Ali Turhan Çağlar","doi":"10.1111/aji.70167","DOIUrl":"https://doi.org/10.1111/aji.70167","url":null,"abstract":"<div>\u0000 \u0000 <p><b>Objective</b>: This study aims to evaluate the clinical applicability and prognostic value of the endothelial activation and stress index (EASIX) in patients with intrahepatic cholestasis of pregnancy (ICP). By investigating the potential of the EASIX score to predict perinatal complications and the clinical course of ICP, we seek to contribute to the improved management and prognosis of ICP patients.</p>\u0000 <p><b>Methods</b>: This retrospective cohort study aimed to investigate the prognostic value of the EASIX in patients diagnosed with ICP at Ankara Etlik City Hospital between January 2023 and January 2025. A total of 121 ICP patients and 133 control patients were included. The EASIX score was calculated using lactate dehydrogenase, creatinine and thrombocyte levels. The relationship between EASIX and perinatal complications, including preterm birth and neonatal distress, was assessed.</p>\u0000 <p><b>Results</b>: The EASIX score was significantly higher in the ICP group compared to controls (<i>p</i> &lt; 0.001), with severe ICP showing the highest EASIX scores (<i>p</i> = 0.019). Cut-off analysis indicated that an EASIX score &gt; 0.64 had a sensitivity of 75% and specificity of 64% for severity prediction (AUC = 0.767, <i>p</i> &lt; 0.001), while a score &gt; 0.69 had a sensitivity of 62% and specificity of 61% for predicting composite adverse perinatal outcomes (AUC = 0.711, <i>p</i> &lt; 0.001).</p>\u0000 <p><b>Conclusion</b>: This study demonstrates that the EASIX score may serve as an important prognostic tool in predicting disease severity and neonatal outcomes in ICP. Given the limited availability of bile acid measurements in some clinics, the EASIX score provides a practical and accessible alternative for clinical use. This study evaluates the prognostic value of the endothelial activation and stress index (EASIX) in intrahepatic cholestasis of pregnancy, highlighting its potential to predict disease severity and neonatal outcomes, offering a practical tool for clinical use.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062508","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":"Re: “Elevated Neutrophil, Lymphocyte, and Platelet Counts as Early Biomarkers of Preeclampsia Risk: A Retrospective Cohort Study”","authors":"Tirayut Veerasathian,&nbsp;Schawanya K. Rattanapitoon,&nbsp;Chadaporn N. Gordon,&nbsp;Nathkapach K. Rattanapitoon","doi":"10.1111/aji.70160","DOIUrl":"https://doi.org/10.1111/aji.70160","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062488","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":"Decidual Cells Induce Release of Free and Exosome-Bound Interferon Epsilon From Vaginal Epithelial Cells","authors":"Emmanuel Amabebe,&nbsp;Lauren S. Richardson,&nbsp;Awanit Kumar,&nbsp;Ramkumar Menon,&nbsp;Brandie D. Taylor","doi":"10.1111/aji.70129","DOIUrl":"https://doi.org/10.1111/aji.70129","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>We tested the hypothesis that oxidative stress (OS)-induced inflammatory response in decidual cells (DECs) may transfer and/or trigger the release of interferon epsilon (IFNε)-positive extracellular vesicles (EVs) from vaginal epithelial cells (VECs) to minimize vaginal disturbances.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>VECs were treated for 48 h under the following conditions: (1) standard VEC media, (2) OS-inducing cigarette smoke extract (CSE); and supernatant from (3) normal/untreated DECs, and (4) CSE-treated DECs. The concentration of cytoplasmic, secreted, and VEC-derived EV bound IFNε (<i>n</i> = 3 each) was measured by enzyme-linked immunosorbent assay (ELISA). EVs were isolated from culture media by cushioned-density gradient ultracentrifugation and characterized by immunoblotting and nanoparticle tracking analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Induction of OS in VECs with CSE increased intracellular IFNε in VECs (<i>p</i> = 0.0007) but not free or EV-bound IFNε compared to control VECs. Exposure to conditioned media from untreated and CSE-treated DECs induced increased intracellular (<i>p</i> = 0.004, <i>p</i> = 0.049) and free IFNε (<i>p</i> = 0.04, <i>p</i> = 0.03) from VECs. VEC-derived EVs (126 ± 11.8 nm) expressed exosome markers, and did not change in size regardless of the treatment but decreased in number due to exposure to untreated (<i>p</i> = 0.004) and CSE-treated DECs (<i>p</i> = 0.025) conditioned media. Furthermore, VEC exosomal IFNε increased by 2.6-fold (<i>p</i> = 0.0001, untreated DECs) and ∼4-fold (<i>p</i> = 0.041, CSE-treated DECs) compared to controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Mucosal immune defense mediated by IFNε may be an innate response by VECs under OS. This was further evidenced by an overall increase in IFNε due to both physiologic and pathologic impact of decidua on VECs. IFNε may indicate a stress response by VECs or paracrine crosstalk between gestational tissues.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037729","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}