Zhiqiang Li, Xiaolian Zhang, Lingwei Peng, Yi Fang, Hongyu Liu, Yang Zhou, Jun Wang, Wenfa Lu
Background
Endometritis is a highly prevalent reproductive disorder in cows, causing serious adverse effects on reproductive performance, which brings huge economic losses to the livestock industry. Staphylococcus aureus is detected in a high proportion of endometritis pathogens (alone or in combinations of infections). Uterine microbial composition plays an important role in endometritis.
Object and Method
In order to determine the role of S. aureus in endometritis, we established an endometritis model using this bacterium and utilized metagenomics to detect the structure and function of the bovine uterine microbiota.
Results
We found that S. aureus infection significantly increased the relative abundance of bacteria such as Escherichia coli, Trueperella pyogenes, and Streptococcus spp., while reducing the relative abundance of Akkermansia and Prevotella bacteria. The functions of microorganisms in the uterus are mainly manifested in metabolic levels, including carbohydrate metabolism, amino acid metabolism, energy metabolism, and lipid metabolism processes. The number of genes continues to increase with the duration of S. aureus infection, which disrupts the balance that maintains the bovine uterine flora.
Conclusion
This study provides a descriptive analysis of changes in the uterine microbiota of cows infected with S. aureus, which contributes to a new understanding of uncultured or unidentified pathogenic bacteria.
{"title":"Response of Bovine Uterine Microbiota to Staphylococcus aureus Infection","authors":"Zhiqiang Li, Xiaolian Zhang, Lingwei Peng, Yi Fang, Hongyu Liu, Yang Zhou, Jun Wang, Wenfa Lu","doi":"10.1111/aji.70178","DOIUrl":"10.1111/aji.70178","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Endometritis is a highly prevalent reproductive disorder in cows, causing serious adverse effects on reproductive performance, which brings huge economic losses to the livestock industry. <i>Staphylococcus aureus</i> is detected in a high proportion of endometritis pathogens (alone or in combinations of infections). Uterine microbial composition plays an important role in endometritis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Object and Method</h3>\u0000 \u0000 <p>In order to determine the role of <i>S. aureus</i> in endometritis, we established an endometritis model using this bacterium and utilized metagenomics to detect the structure and function of the bovine uterine microbiota.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that <i>S. aureus</i> infection significantly increased the relative abundance of bacteria such as <i>Escherichia coli</i>, <i>Trueperella pyogenes</i>, and <i>Streptococcus</i> spp., while reducing the relative abundance of <i>Akkermansia</i> and <i>Prevotella</i> bacteria. The functions of microorganisms in the uterus are mainly manifested in metabolic levels, including carbohydrate metabolism, amino acid metabolism, energy metabolism, and lipid metabolism processes. The number of genes continues to increase with the duration of <i>S. aureus</i> infection, which disrupts the balance that maintains the bovine uterine flora.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides a descriptive analysis of changes in the uterine microbiota of cows infected with <i>S. aureus</i>, which contributes to a new understanding of uncultured or unidentified pathogenic bacteria.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436659","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}
Sallie L. Fell, Sydney M. Nemphos, James E. Prusak, Amitinder Kaur, Jamie O. Lo, Jennifer A. Manuzak
Neutrophils, traditionally recognized for their role in innate immunity, have emerged as a key cell population at the maternal-fetal interface, during both uncomplicated and pathological pregnancies. Neutrophil effector functions, including phagocytosis, neutrophil extracellular trap formation, and degranulation, can play protective roles, such as preventing infection and facilitating tissue remodeling during pregnancy. However, these effector functions may also contribute to excessive inflammation, tissue damage, and adverse pregnancy outcomes in the context of sterile inflammation or maternal infection, underscoring the dual nature of neutrophils at the maternal-fetal interface. In this review, we examine the paradoxical nature of neutrophils at the maternal-fetal interface. Further, the protective and deleterious roles of neutrophils during pregnancy are evaluated in the context of bacterial, viral, and parasitic infections. Insights from this review are anticipated to inform basic and clinical research aimed at identifying neutrophils or neutrophil components as biomarkers and therapeutic targets in obstetric conditions and infectious diseases during pregnancy.
{"title":"Neutrophils at the Maternal-Fetal Interface: Agents of Protection or Destruction?","authors":"Sallie L. Fell, Sydney M. Nemphos, James E. Prusak, Amitinder Kaur, Jamie O. Lo, Jennifer A. Manuzak","doi":"10.1111/aji.70181","DOIUrl":"10.1111/aji.70181","url":null,"abstract":"<p>Neutrophils, traditionally recognized for their role in innate immunity, have emerged as a key cell population at the maternal-fetal interface, during both uncomplicated and pathological pregnancies. Neutrophil effector functions, including phagocytosis, neutrophil extracellular trap formation, and degranulation, can play protective roles, such as preventing infection and facilitating tissue remodeling during pregnancy. However, these effector functions may also contribute to excessive inflammation, tissue damage, and adverse pregnancy outcomes in the context of sterile inflammation or maternal infection, underscoring the dual nature of neutrophils at the maternal-fetal interface. In this review, we examine the paradoxical nature of neutrophils at the maternal-fetal interface. Further, the protective and deleterious roles of neutrophils during pregnancy are evaluated in the context of bacterial, viral, and parasitic infections. Insights from this review are anticipated to inform basic and clinical research aimed at identifying neutrophils or neutrophil components as biomarkers and therapeutic targets in obstetric conditions and infectious diseases during pregnancy.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399505","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}
This study aimed to identify potential biomarkers for preterm birth (PTB) and construct a multidimensional risk prediction model integrating clinical and proteomic data, with a focus on CCL28.
Materials and Methods
Pregnant women were enrolled and categorized into PTB and term birth (TB) groups. Plasma and placental samples were analyzed using OLINK proteomics, ELISA, and immunohistochemistry. Logistic regression and nomogram modeling were employed to assess predictive markers, while ROC curve analysis was used to evaluate model performance.
Results
Proteomic analysis revealed significantly lower CCL28 levels in PTB compared to TB (p < 0.01), which was validated by ELISA (p < 0.0001). Immunohistochemistry confirmed reduced CCL28 expression in PTB placental tissue. Multivariate logistic regression identified CCL28 as an independent predictor of PTB (OR = 0.150, p = 0.01). The developed nomogram, incorporating CCL28 levels and clinical variables, demonstrated strong predictive ability (AUC = 0.841).
Conclusion
CCL28 was identified as a key biomarker for PTB prediction. The integrated prediction model enhanced early risk assessment, providing a valuable tool for targeted clinical interventions in high-risk pregnancies.
{"title":"Development of a Preterm Birth Risk Prediction Model Based on CCL28 Biomarker Selection and Multidimensional Data Integration","authors":"Yingying Li, Ning Xu, Jie Zhang, Guocheng Liu","doi":"10.1111/aji.70175","DOIUrl":"10.1111/aji.70175","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aimed to identify potential biomarkers for preterm birth (PTB) and construct a multidimensional risk prediction model integrating clinical and proteomic data, with a focus on CCL28.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Pregnant women were enrolled and categorized into PTB and term birth (TB) groups. Plasma and placental samples were analyzed using OLINK proteomics, ELISA, and immunohistochemistry. Logistic regression and nomogram modeling were employed to assess predictive markers, while ROC curve analysis was used to evaluate model performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Proteomic analysis revealed significantly lower CCL28 levels in PTB compared to TB (<i>p</i> < 0.01), which was validated by ELISA (<i>p</i> < 0.0001). Immunohistochemistry confirmed reduced CCL28 expression in PTB placental tissue. Multivariate logistic regression identified CCL28 as an independent predictor of PTB (OR = 0.150, <i>p</i> = 0.01). The developed nomogram, incorporating CCL28 levels and clinical variables, demonstrated strong predictive ability (AUC = 0.841).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CCL28 was identified as a key biomarker for PTB prediction. The integrated prediction model enhanced early risk assessment, providing a valuable tool for targeted clinical interventions in high-risk pregnancies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399462","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}
Endometriosis (ENDO) is a painful, chronic gynecological disease widely affecting women globally. While traditionally classified as a hormonal disorder, ENDO is now increasingly recognized as a multifaceted immune-mediated syndrome driven by chronic inflammation and immune tolerance. It is associated with painful symptoms, infertility, and potential malignant transformation. This study provides a comprehensive review of the immunological literature from electronic databases, focusing on the roles of innate and adaptive immune cell dysfunction in ENDO progression, including Neutrophil Extracellular Traps (NETs), macrophages, and lymphocytes. The pathology is governed by a dysregulated immunological landscape, specifically involving elevated NETs, the prevalence of immunosuppressive M2 macrophages, and compromised Natural Killer (NK) cell and T lymphocyte activity. These elements establish a tumor-like microenvironment through the activation of immune checkpoints and metabolic reprogramming. The chemokine IL-8 is highlighted as a central catalyst promoting NETosis and inflammation, driving fibrosis, lesion invasiveness, and reproductive failure. These immune circuits may also contribute to the risk of Endometriosis-Associated Ovarian Cancers. Reframing ENDO through this immunological paradigm provides an integrated model that incorporates its inflammatory, fibrotic, and carcinogenic features. This understanding reveals promising, non-hormonal therapeutic strategies targeting NETs, macrophage modulators, and immunological checkpoints for disease management and fertility preservation.
{"title":"Reframing Endometriosis: Interplay of NETs, Macrophages, and Lymphocytes at the Crossroads of Disease Progression, Infertility, and Malignant Transformation","authors":"Megha M. Anchan, Rahul Dutta","doi":"10.1111/aji.70179","DOIUrl":"10.1111/aji.70179","url":null,"abstract":"<div>\u0000 \u0000 <p>Endometriosis (ENDO) is a painful, chronic gynecological disease widely affecting women globally. While traditionally classified as a hormonal disorder, ENDO is now increasingly recognized as a multifaceted immune-mediated syndrome driven by chronic inflammation and immune tolerance. It is associated with painful symptoms, infertility, and potential malignant transformation. This study provides a comprehensive review of the immunological literature from electronic databases, focusing on the roles of innate and adaptive immune cell dysfunction in ENDO progression, including Neutrophil Extracellular Traps (NETs), macrophages, and lymphocytes. The pathology is governed by a dysregulated immunological landscape, specifically involving elevated NETs, the prevalence of immunosuppressive M2 macrophages, and compromised Natural Killer (NK) cell and T lymphocyte activity. These elements establish a tumor-like microenvironment through the activation of immune checkpoints and metabolic reprogramming. The chemokine IL-8 is highlighted as a central catalyst promoting NETosis and inflammation, driving fibrosis, lesion invasiveness, and reproductive failure. These immune circuits may also contribute to the risk of Endometriosis-Associated Ovarian Cancers. Reframing ENDO through this immunological paradigm provides an integrated model that incorporates its inflammatory, fibrotic, and carcinogenic features. This understanding reveals promising, non-hormonal therapeutic strategies targeting NETs, macrophage modulators, and immunological checkpoints for disease management and fertility preservation.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145375833","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}
Zhaowei Cai, Rongju Liu, Li Zhao, Liling Zhou, Qingyang Li, Hongmei He
Problem
Polycystic ovary syndrome (PCOS) stands as a multifaceted endocrine disorder with implications beyond reproductive health, encompassing metabolic and immunological dimensions. This study delves into the immunological alterations within T cells in a murine PCOS model, unraveling novel insights into the molecular mechanisms contributing to T cell dysfunction.
Method of Study
A PCOS model was established in mice, followed by isolating T cells. Isolated T cells were activated by anti-CD3 and anti-CD28 antibodies. Cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA) assay, and carboxyfluorescein succinimidyl ester (CFSE) dye was utilized for proliferation detection. Flow cytometry was utilized for analyzing exhaustion markers. RNA methylation analysis was determined by methylated RNA immunoprecipitation (Me-RIP) assay.
Results
In the PCOS mouse model, T cells exhibited a state of exhaustion, including impaired activation, reduced cytokine secretion, and decreased proliferative capacity. Particularly, the expression of T cell immunoreceptor with Ig and ITIM domain (TIGIT) molecules on the surface of T cells was significantly increased, which was associated with T cell exhaustion. The stability of TIGIT mRNA was enhanced due to the increased level of N6 RNA methylation, in which the methyltransferase-like 3 (METTL3) methyltransferase played a key role. Experiments showed that by inhibiting N6-methyladenosine (M6A) methylation or knocking out METTL3, the activation phenotype of PCOS T cells could be reversed, and cytokine secretion and proliferative capacity could be restored.
Conclusions
Although acknowledging study limitations, such as the murine model's partial recapitulation of human PCOS complexity, this research provides a foundation for future investigations into the specific molecular mechanisms governing T cell function and potential therapeutic targets within the N6 RNA methylation pathway.
{"title":"Immunological Dynamics in PCOS T Cell Exhaustion TIGIT Upregulation Regulated by METTL3-Mediated N6 RNA Methylation","authors":"Zhaowei Cai, Rongju Liu, Li Zhao, Liling Zhou, Qingyang Li, Hongmei He","doi":"10.1111/aji.70180","DOIUrl":"https://doi.org/10.1111/aji.70180","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Polycystic ovary syndrome (PCOS) stands as a multifaceted endocrine disorder with implications beyond reproductive health, encompassing metabolic and immunological dimensions. This study delves into the immunological alterations within T cells in a murine PCOS model, unraveling novel insights into the molecular mechanisms contributing to T cell dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>A PCOS model was established in mice, followed by isolating T cells. Isolated T cells were activated by anti-CD3 and anti-CD28 antibodies. Cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA) assay, and carboxyfluorescein succinimidyl ester (CFSE) dye was utilized for proliferation detection. Flow cytometry was utilized for analyzing exhaustion markers. RNA methylation analysis was determined by methylated RNA immunoprecipitation (Me-RIP) assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the PCOS mouse model, T cells exhibited a state of exhaustion, including impaired activation, reduced cytokine secretion, and decreased proliferative capacity. Particularly, the expression of T cell immunoreceptor with Ig and ITIM domain (TIGIT) molecules on the surface of T cells was significantly increased, which was associated with T cell exhaustion. The stability of TIGIT mRNA was enhanced due to the increased level of N6 RNA methylation, in which the methyltransferase-like 3 (METTL3) methyltransferase played a key role. Experiments showed that by inhibiting N6-methyladenosine (M6A) methylation or knocking out METTL3, the activation phenotype of PCOS T cells could be reversed, and cytokine secretion and proliferative capacity could be restored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although acknowledging study limitations, such as the murine model's partial recapitulation of human PCOS complexity, this research provides a foundation for future investigations into the specific molecular mechanisms governing T cell function and potential therapeutic targets within the N6 RNA methylation pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367069","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}
This meta-analysis (MA) systematically evaluated the application value of systemic immune-inflammation index (SII) in the prognosis of patients with gynecological tumors. Electronic databases including PubMed, Embase, Cochrane Library, Web of Science, Elsevier, and Wiley were searched for randomized controlled trials (RCTs) of SII according to inclusion and exclusion criteria, with the search period extending from the inception of the databases to November 2024. Clinical outcomes included overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). The quality of the included articles was assessed adopting the Cochrane systematic review method, and MA was conducted adopting Stata 17.0 software. A total of eight studies (10 trials) were included, with high SII having an observable negative impact on OS [Tau2 = 0.20, 95% confidence interval (CI): 1.30–2.58; Z = 3.47, p = 0.0005]. High SII had an observable negative impact on DFS and PFS (Tau2 = 0.08, 95% CI: 1.25–1.97; Z = 3.89, p = 0.0001). High SII had an observable negative impact on DMFS (95% CI: 1.20–1.86; Z = 3.54, p = 0.0004). The MA results indicate that a high SII index predicts poor survival outcomes in patients with gynecological tumors and is an effective indicator for prognosis in clinical practice.
本meta分析（MA）系统评价全身免疫炎症指数（SII）在妇科肿瘤患者预后中的应用价值。检索PubMed、Embase、Cochrane Library、Web of Science、Elsevier和Wiley等电子数据库，按照纳入和排除标准检索SII的随机对照试验（RCTs），检索时间从数据库建立之初至2024年11月。临床结果包括总生存期（OS）、无病生存期（DFS）、无进展生存期（PFS）和无远处转移生存期（DMFS）。采用Cochrane系统评价法评价纳入文献的质量，采用Stata 17.0软件进行meta分析。共纳入8项研究（10项试验），高SII对OS有可观察到的负面影响[Tau2 = 0.20, 95%可信区间（CI）： 1.30-2.58；Z = 3.47, p = 0.0005]。高SII对DFS和PFS有明显的负面影响（Tau2 = 0.08, 95% CI: 1.25-1.97; Z = 3.89, p = 0.0001）。高SII对DMFS有明显的负面影响（95% CI: 1.20-1.86; Z = 3.54, p = 0.0004）。MA结果提示，高SII指数预示着妇科肿瘤患者的生存结局较差，是临床判断预后的有效指标。
{"title":"Prognostic Value of Systemic Immune-Inflammation Index in Patients With Gynecological Tumors: A Systematic Review and Meta-Analysis","authors":"Feng Guo, Hao Peng, Hao Hu, Jia Liu","doi":"10.1111/aji.70170","DOIUrl":"10.1111/aji.70170","url":null,"abstract":"<div>\u0000 \u0000 <p>This meta-analysis (MA) systematically evaluated the application value of systemic immune-inflammation index (SII) in the prognosis of patients with gynecological tumors. Electronic databases including PubMed, Embase, Cochrane Library, Web of Science, Elsevier, and Wiley were searched for randomized controlled trials (RCTs) of SII according to inclusion and exclusion criteria, with the search period extending from the inception of the databases to November 2024. Clinical outcomes included overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). The quality of the included articles was assessed adopting the Cochrane systematic review method, and MA was conducted adopting Stata 17.0 software. A total of eight studies (10 trials) were included, with high SII having an observable negative impact on OS [Tau<sup>2</sup> = 0.20, 95% confidence interval (CI): 1.30–2.58; <i>Z</i> = 3.47, <i>p</i> = 0.0005]. High SII had an observable negative impact on DFS and PFS (Tau<sup>2</sup> = 0.08, 95% CI: 1.25–1.97; <i>Z</i> = 3.89, <i>p</i> = 0.0001). High SII had an observable negative impact on DMFS (95% CI: 1.20–1.86; <i>Z</i> = 3.54, <i>p</i> = 0.0004). The MA results indicate that a high SII index predicts poor survival outcomes in patients with gynecological tumors and is an effective indicator for prognosis in clinical practice.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342830","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}
<div> <section> <h3> Problem</h3> <p>Many studies have demonstrated the negative impact of high rates of NK cytotoxicity (NKc) on reproductive outcomes, as well as the beneficial effects of intravenous immunoglobulin or intravenous lipid emulsion, specifically in these patients.</p> </section> <section> <h3> Method of Study</h3> <p>NKc was measured in PBMCs against K562 by flow cytometry. For retrospective analysis, 2250 cycles of ET were selected and divided into four groups according to NKc levels and treatment: normal (nNKc, <i>n</i> = 587), elevated (eNKc, <i>n</i> = 615), eNKc with IvIg treatment (<i>n</i> = 231), and eNKc with IL treatment (<i>n</i> = 180). Patients were <36 years old, negative for anticardiolipin antibodies, and did not have insufficient endometrium, thrombotic disorders, uterine abnormalities, or obesity. Patients aged 36–39 years (<i>n</i> = 359) and 39–42 years (<i>n</i> = 279) were analyzed separately using a similar approach.</p> </section> <section> <h3> Results</h3> <p>Patients with eNKc, in addition to having reduced clinical pregnancy rates (CPR) 26.99%, had increased levels of pregnancy failures (PF) 36.7% and a preterm birth rate (PBR) 13.3%, compared to nNKc patients (34.07%, 23.5%, and 3.26%, respectively). As a result, patients with eNKc had a reduced live birth rate (LBR) (17.0%), compared to nNKc patients (26.06%, OR: 1.720, <i>p</i> < 0.0002).</p> <p>Both IvIg and IL treatment resulted in increased CPR (44.15% and 39.44%) and LBR (32.03% and 32.22%) compared to patients with eNKc without treatment. IvIg treatment increased CPR even compared to patients with nNKc. However, the pregnancy failure rate (PFR) in IvIg-treated patients was not significantly reduced compared to non-treated patients with eNKc. In contrast, IL-treated patients had significantly decreased PFR compared to patients with eNKc without treatment. As a result, both treatments (IvIg and IL) led to an LBR similar to that of nNKc. Both therapies (IvIg and IL) did not affect the Preterm birth rate, which remained relatively high (14.86% and 13.79%, respectively). However, the frequency of antenatal or prenatal fetal death was the same in all groups.</p> <p>In patients aged 36–39 years, the results were quite similar, although the PFR in all groups was already significantly higher. However, in patients aged 39–42 years, the negative impact of eNKc was no longer significant, as high PFR and low LBR were also found in patients with nNKc. Nevertheless, even in this group, IvIg therapy led to higher LBR rates compared to eNKc without therapy.</p> </section> <section> <h3> Conclusions</h3>
问题：许多研究已经证明高NK细胞毒性（NKc）对生殖结果的负面影响，以及静脉注射免疫球蛋白或静脉注射脂质乳的有益作用，特别是在这些患者中。研究方法：采用流式细胞术测定PBMCs中NKc对K562的作用。回顾性分析，选取2250个ET周期，根据NKc水平和治疗分为4组：正常组（nNKc, n = 587）、升高组（eNKc, n = 615）、IvIg组（n = 231）和IL组（n = 180）。结果：与nNKc患者相比，eNKc患者除了临床妊娠率（CPR）降低26.99%外，妊娠失败（PF）水平增加36.7%，早产率（PBR）增加13.3%（分别为34.07%，23.5%和3.26%）。结果，eNKc患者的活产率（LBR）（17.0%）低于nNKc患者（26.06%,OR: 1.720, p < 0.0002）。与未治疗的eNKc患者相比，IvIg和IL治疗均导致CPR（44.15%和39.44%）和LBR（32.03%和32.22%）增加。即使与nNKc患者相比，IvIg治疗也增加了CPR。然而，与未接受治疗的eNKc患者相比，接受ivig治疗的患者的妊娠失败率（PFR）并未显著降低。相比之下，与未经治疗的eNKc患者相比，接受il治疗的患者的PFR显著降低。结果，两种治疗（IvIg和IL）导致的LBR与nNKc相似。两种治疗（IvIg和IL）都没有影响早产率，早产率仍然相对较高（分别为14.86%和13.79%）。然而，在所有组中，产前或胎儿死亡的频率是相同的。在36-39岁的患者中，结果非常相似，尽管所有组的PFR已经明显更高。然而，在39-42岁的患者中，eNKc的负面影响不再显著，因为在nNKc患者中也发现了高PFR和低LBR。然而，即使在这一组中，与未治疗的eNKc相比，IvIg治疗导致更高的LBR率。结论：我们的研究结果强调了高水平NK细胞毒性对生殖过程各个阶段的负面影响。该组经IvIg和IL治疗后LBR明显改善。与nNKc患者相比，IvIg的强度似乎是基于CPR的大幅增加，而IL的有效性更多地是基于PF率的显著降低。此外，IvIg的疗效似乎并不局限于eNKc患者。IvIg和IL联合治疗可提高NK活性升高患者的治疗效果。
{"title":"Intravenous Immunoglobulin or Intravenous Lipid Emulsion Therapy in Patients With Elevated NK Cytotoxicity Improves Live Birth Rates in Different Ways","authors":"Boris Dons'koi, Iryna Kononenko, Vira Sirenko, Natalia Bodnar, Andrii Serbyn, Anzhela Kozachok, Yulia Brovarska","doi":"10.1111/aji.70176","DOIUrl":"10.1111/aji.70176","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Many studies have demonstrated the negative impact of high rates of NK cytotoxicity (NKc) on reproductive outcomes, as well as the beneficial effects of intravenous immunoglobulin or intravenous lipid emulsion, specifically in these patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>NKc was measured in PBMCs against K562 by flow cytometry. For retrospective analysis, 2250 cycles of ET were selected and divided into four groups according to NKc levels and treatment: normal (nNKc, <i>n</i> = 587), elevated (eNKc, <i>n</i> = 615), eNKc with IvIg treatment (<i>n</i> = 231), and eNKc with IL treatment (<i>n</i> = 180). Patients were <36 years old, negative for anticardiolipin antibodies, and did not have insufficient endometrium, thrombotic disorders, uterine abnormalities, or obesity. Patients aged 36–39 years (<i>n</i> = 359) and 39–42 years (<i>n</i> = 279) were analyzed separately using a similar approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with eNKc, in addition to having reduced clinical pregnancy rates (CPR) 26.99%, had increased levels of pregnancy failures (PF) 36.7% and a preterm birth rate (PBR) 13.3%, compared to nNKc patients (34.07%, 23.5%, and 3.26%, respectively). As a result, patients with eNKc had a reduced live birth rate (LBR) (17.0%), compared to nNKc patients (26.06%, OR: 1.720, <i>p</i> < 0.0002).</p>\u0000 \u0000 <p>Both IvIg and IL treatment resulted in increased CPR (44.15% and 39.44%) and LBR (32.03% and 32.22%) compared to patients with eNKc without treatment. IvIg treatment increased CPR even compared to patients with nNKc. However, the pregnancy failure rate (PFR) in IvIg-treated patients was not significantly reduced compared to non-treated patients with eNKc. In contrast, IL-treated patients had significantly decreased PFR compared to patients with eNKc without treatment. As a result, both treatments (IvIg and IL) led to an LBR similar to that of nNKc. Both therapies (IvIg and IL) did not affect the Preterm birth rate, which remained relatively high (14.86% and 13.79%, respectively). However, the frequency of antenatal or prenatal fetal death was the same in all groups.</p>\u0000 \u0000 <p>In patients aged 36–39 years, the results were quite similar, although the PFR in all groups was already significantly higher. However, in patients aged 39–42 years, the negative impact of eNKc was no longer significant, as high PFR and low LBR were also found in patients with nNKc. Nevertheless, even in this group, IvIg therapy led to higher LBR rates compared to eNKc without therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290732","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 “Decidual Cells Induce Release of Free and Exosome-Bound Interferon Epsilon From Vaginal Epithelial Cells”","authors":"Shyam Sundar Sah, Abhishek Kumbhalwar","doi":"10.1111/aji.70177","DOIUrl":"10.1111/aji.70177","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273327","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}
Şebnem Karagün, Hamza Yıldız, Yusuf Dal, Ahmet Zeki Nessar, Sefanur Gamze Karaca, Mürşide Çevikoğlu Kıllı, Ayhan Coşkun
Objective
To evaluate the effect of magnesium sulfate (MgSO4) therapy on dynamic changes in maternal inflammation-based hematologic indices and their predictive value for neonatal outcomes in high-risk pregnancies.
Methods
We conducted a retrospective cohort study involving 236 singleton pregnancies treated with MgSO4 for either fetal neuroprotection or seizure prophylaxis. Pre- and 24-h post-treatment complete blood count (CBC)—derived inflammatory markers (including neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], systemic inflammation response index [SIRI], and mean platelet volume [MPV]) were compared. Percentage change (Δ) values were calculated. Associations between these Δ-values and adverse perinatal outcomes were analyzed using correlation tests and ROC curves.
Results
Following MgSO4 administration, significant alterations were observed in maternal inflammatory markers: NLR (+12.2%), WBC (+11.7%), SIRI (+25.6%) increased, whereas PLR (−9.7%), LMR (−6.1%), and platelet count (−9.6%) decreased (all p < 0.05). ΔNLR, ΔMPV, and ΔWBC correlated negatively with gestational age and birth weight, and positively with NICU admission. ROC analysis identified ΔNLR ≥ −15.132 as a predictor of NICU admission (AUC = 0.609, p = 0.016).
Conclusion
Magnesium sulfate induces measurable changes in maternal inflammatory profiles. These dynamic hematologic shifts—especially in NLR and MPV—may carry limited predictive value for adverse neonatal outcomes. Monitoring ∆-inflammatory indices could support exploratory efforts in risk stratification, but further validation is required before clinical application.
{"title":"Magnesium Sulfate–Mediated Inflammatory Modulation in High-Risk Pregnancies: Dynamic Shifts in CBC-Derived Markers Predict Neonatal Outcomes","authors":"Şebnem Karagün, Hamza Yıldız, Yusuf Dal, Ahmet Zeki Nessar, Sefanur Gamze Karaca, Mürşide Çevikoğlu Kıllı, Ayhan Coşkun","doi":"10.1111/aji.70172","DOIUrl":"10.1111/aji.70172","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To evaluate the effect of magnesium sulfate (MgSO<sub>4</sub>) therapy on dynamic changes in maternal inflammation-based hematologic indices and their predictive value for neonatal outcomes in high-risk pregnancies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective cohort study involving 236 singleton pregnancies treated with MgSO<sub>4</sub> for either fetal neuroprotection or seizure prophylaxis. Pre- and 24-h post-treatment complete blood count (CBC)—derived inflammatory markers (including neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], systemic inflammation response index [SIRI], and mean platelet volume [MPV]) were compared. Percentage change (Δ) values were calculated. Associations between these Δ-values and adverse perinatal outcomes were analyzed using correlation tests and ROC curves.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Following MgSO<sub>4</sub> administration, significant alterations were observed in maternal inflammatory markers: NLR (+12.2%), WBC (+11.7%), SIRI (+25.6%) increased, whereas PLR (−9.7%), LMR (−6.1%), and platelet count (−9.6%) decreased (all <i>p </i>< 0.05). ΔNLR, ΔMPV, and ΔWBC correlated negatively with gestational age and birth weight, and positively with NICU admission. ROC analysis identified ΔNLR ≥ −15.132 as a predictor of NICU admission (AUC = 0.609, <i>p</i> = 0.016).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Magnesium sulfate induces measurable changes in maternal inflammatory profiles. These dynamic hematologic shifts—especially in NLR and MPV—may carry limited predictive value for adverse neonatal outcomes. Monitoring ∆-inflammatory indices could support exploratory efforts in risk stratification, but further validation is required before clinical application.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273373","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}
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