American Journal of Reproductive Immunology最新文献_第9页

Outcomes of Ultimpro Testing Implementation for Patients With Unexplained Recurrent Implantation Failure: A Single-Center Retrospective Cohort Study 用于不明原因复发性植入失败患者的Ultimpro检测结果：一项单中心回顾性队列研究

IF 2.4 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2025-07-31 DOI: 10.1111/aji.70131

Genevieve Genest, Alyssa Hochberg, Martine Boivin, Alexie Ferreira, Zhiyang Liu, Coralie Beauchamp, Marc Beltempo, Michael H. Dahan, Elias M. Dahdouh, Ezgi Demirtas, Robert Hemmings, Wael Jamal, Isaac-Jacques Kadoch, Louise Lapensée, Neal Mahutte, Simon Phillips, Shauna Reinblatt, Camille Sylvestre, William Buckett, Bruce D. Mazer, Ciriaco A. Piccirillo

Problem

A proportion of patients with unexplained recurrent implantation failure (uRIF) may have endometrial immune dysregulation amenable to treatment. Ultimpro (Matrice lab Innove, Paris, France) is an endometrial immunophenotype test which identifies the absence or presence and type of immune dysregulation, proposing personalized protocol adjustments for a future embryo transfer (ET).

Method of Study

2.5-year single-center retrospective cohort analysis of 121 patients who underwent Ultimpro testing as a pilot study (January 2021—May 2023). Group 1 included 93 patients with uRIF, and Group 2 included 28 patients without RIF. Outcomes from Group 1 were compared to Group 3, a control cohort of 94 uRIF patients, outcomes for Group 2 were compared to Canadian average ongoing pregnancy rates (OPR) per ET. Primary outcome was pregnancy >32 weeks or live birth. Statistical analyses included the Student t-test or Mann–Whitney U test for continuous variables and the Fisher exact test for categorical data.

Results

In Group 1, 46/93 (49.5%) patients had a successful pregnancy compared to control (31/94 [33%], p = 0.026); when stratifying for RIF severity, patients with ≥ 5 failed blastocyst transfers benefitted most from Ultimpro (21/38 [55.3%] vs. control 5/25 (20.0%), p = 0.0084). In Group 2, rates of OPR per ET with Ultimpro recommendations did not differ from outcomes for non-RIF patients (9/28 [32.1%]; 95% CI: 0.15–0.52 vs. 46.2%).

Conclusions

In patients with uRIF, our preliminary findings suggest that application of Ultimpro recommendations was associated with a higher rate of successful outcomes; this was not the case for patients without RIF. These findings provide the rationale for an independent randomized controlled trial evaluating the large-scale use of Ultimpro in patients with uRIF.

部分不明原因复发性着床失败（uRIF）患者可能存在可治疗的子宫内膜免疫失调。Ultimpro （matrix lab Innove, Paris, France）是一种子宫内膜免疫表型测试，可识别免疫失调的存在或缺失和类型，为未来的胚胎移植（ET）提出个性化的方案调整。研究方法：对121例接受Ultimpro检测的患者进行2.5年单中心回顾性队列分析，作为一项先导研究（2021年1月- 2023年5月）。组1包括93例uRIF患者，组2包括28例无RIF患者。将第1组的结果与第3组（94例uRIF患者的对照队列）的结果进行比较，第2组的结果与加拿大每次ET的平均持续妊娠率（OPR）进行比较。主要结果为妊娠32周或活产。统计分析包括连续变量的学生t检验或Mann-Whitney U检验和分类数据的Fisher精确检验。结果1组46/93例（49.5%）患者妊娠成功，对照组（31/94 [33%],p = 0.026）；当对RIF严重程度进行分层时，≥5个囊胚移植失败的患者从Ultimpro中获益最多（21/38 [55.3%]vs.对照组5/25 (20.0%),p = 0.0084）。在第2组中，Ultimpro推荐的每ET的OPR率与非rif患者的结果没有差异(9/28 [32.1%]；95% CI: 0.15-0.52 vs. 46.2%)。在uRIF患者中，我们的初步研究结果表明，应用Ultimpro推荐与更高的成功率相关；对于没有RIF的患者，情况并非如此。这些发现为一项独立的随机对照试验提供了依据，该试验评估了Ultimpro在uRIF患者中的大规模使用。

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引用次数: 0

Elevated Neutrophil, Lymphocyte, and Platelet Counts as Early Biomarkers of Preeclampsia Risk: A Retrospective Cohort Study 中性粒细胞、淋巴细胞和血小板计数升高作为子痫前期风险的早期生物标志物：一项回顾性队列研究

IF 2.4 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2025-07-30 DOI: 10.1111/aji.70137

Ying-Ling Yao, Zhou Xu, Rui Xiao, Er-Han Li, Yong-Jia Zhang, Li-Yang Zhou, Zhao-Hui Zhong, Li-Juan Fu, Hong-Bo Qi, Xiao-Bin Wu, Yu-Bin Ding

Objective

This study aimed to evaluate the association between peripheral immune markers during gestational weeks 11–28 and the risk of preeclampsia (PE), and to explore potential causal relationships using Mendelian randomization (MR).

Methods

We conducted a retrospective cohort study involving 19, 028 singleton pregnancies between January 2020 and December 2023. Peripheral immune markers, including neutrophils, lymphocytes, monocytes, and platelets, and derived indices, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII), were analyzed in relation to PE incidence. Subgroup and interaction analyses were further stratified by maternal age, prepregnancy BMI, gestational age at blood test, and gestational diabetes mellitus (GDM). Causality was assessed using MR with the inverse-variance weighted multiplicative random effects (IVW MRE) method.

Results

Elevated neutrophil (RR per SD = 1.20; 95% CI: 1.09–1.33; P < 0.001), lymphocyte (RR per SD = 1.16; 95% CI: 1.06–1.27; P = 0.002), and platelet (RR per SD = 1.19; 95% CI: 1.07–1.31; P = 0.001) counts were significantly associated with increased PE risk. Associations were stronger in women aged ≥35 years, with a significant interaction for platelet count (P = 0.004). MR analysis revealed no causal link between genetically predicted immune cell counts and PE.

Conclusion

Higher peripheral neutrophil, lymphocyte, and platelet levels are associated with increased PE risk, particularly among older pregnant women. While MR analysis did not support a causal effect, these immune markers may serve as accessible early indicators and offer insight into PE pathogenesis.

目的本研究旨在评估妊娠11-28周外周免疫标记物与先兆子痫（PE）风险之间的关系，并利用孟德尔随机化（MR）方法探讨潜在的因果关系。方法：我们对2020年1月至2023年12月期间19028例单胎妊娠进行了回顾性队列研究。外周免疫标志物，包括中性粒细胞、淋巴细胞、单核细胞和血小板，以及衍生指标，如中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）、淋巴细胞与单核细胞比值（LMR）和全身免疫炎症指数（SII），分析与PE发病率的关系。亚组和相互作用分析进一步按产妇年龄、孕前BMI、血检胎龄和妊娠期糖尿病（GDM）进行分层。因果关系评估使用磁共振与反方差加权乘法随机效应（IVW MRE）方法。结果中性粒细胞升高(RR / SD = 1.20；95% ci: 1.09-1.33；P & lt;0.001)，淋巴细胞(RR / SD = 1.16；95% ci: 1.06-1.27；P = 0.002)，血小板(RR / SD = 1.19；95% ci: 1.07-1.31；P = 0.001)计数与PE风险增加显著相关。在年龄≥35岁的女性中，相关性更强，与血小板计数有显著的相互作用（P = 0.004）。磁共振分析显示，基因预测的免疫细胞计数与PE之间没有因果关系。结论外周中性粒细胞、淋巴细胞和血小板水平升高与PE风险增加有关，尤其是在高龄孕妇中。虽然MR分析不支持因果关系，但这些免疫标记物可以作为早期指标，并为PE的发病机制提供见解。

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引用次数: 0

Exosomes Derived From Calycosin-Exposed Prostate Stromal Cells Inhibit Lipopolysaccharide-Induced Epithelial Cells Inflammatory Injury 暴露于花萼异黄酮的前列腺基质细胞外泌体抑制脂多糖诱导的上皮细胞炎症损伤

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2025-07-28 DOI: 10.1111/aji.70113

Ming Li, Wenping Yao, Yingying Sun, Heng Wang

Background

Chronic prostatitis (CP) is a common and serious disorder characterized by unknown pathogenic mechanisms and recurrent symptoms. Exosomes isolated from prostate stromal cells can also be used to treat chronic inflammation. This study aimed to elucidate the mechanism of action of Calycosin (CA) during CP therapy.

Material and Methods

LPS volume of 10 µg/mL was applied for constructing the cell models of CP. RWPE-1 cells were co-cultivated with exosomes isolated from CA elicited-WPMY-1 cells (CA-WPMY-1-exo). Exosomes isolated from WPMY-1 cells were identified by TEM, NTA, and western blotting. MTT and flow cytometry analyses were performed to evaluate cell viability and apoptosis, respectively. The secretion of inflammatory cytokines was measured using ELISA. The expressions of cleaved-Caspase3, Caspase3, p-p65, and p65 were determined by western blotting.

Results

LPS treatment decreased RWPE-1 cell viability and stimulated more apoptotic cells, which was partly abolished by CA treatment in a dose-dependent manner. Furthermore, CA alleviated the LPS-induced inflammatory response in a dose-dependent manner. NC-WPMY-1 and CA-WPMY-1 markedly enhanced RWPE-1 cell viability. We also found that both NC-WPMY-1-exo and CA-WPMY-1-exo reversed the effects of LPS on RWPE-1 cell viability, apoptosis, and inflammation. The effect of CA-WPMY-1-exo on RWPE-1 cells was more significant than that of NC-WPMY-1-exo.

Conclusion

Exosomes derived from CA-exposed prostate stromal cells were identified as significant mediators of CP by inhibiting LPS-induced epithelial cells inflammatory injury.

慢性前列腺炎（CP）是一种常见的严重疾病，其发病机制尚不清楚，且症状反复发作。从前列腺基质细胞中分离的外泌体也可用于治疗慢性炎症。本研究旨在阐明毛蕊异黄酮（Calycosin， CA）在CP治疗中的作用机制。材料与方法采用体积为10µg/mL的LPS构建CP细胞模型，RWPE-1细胞与CA诱导的wpmy -1细胞（CA- wpmy -1-exo）分离的外泌体共培养。从WPMY-1细胞分离的外泌体通过TEM、NTA和western blotting进行鉴定。MTT和流式细胞术分析分别评估细胞活力和凋亡。采用ELISA法检测炎症因子的分泌。western blotting检测cleaved-Caspase3、Caspase3、p-p65、p65的表达。结果LPS处理降低了RWPE-1细胞活力，刺激了更多的凋亡细胞，CA处理部分消除了凋亡细胞，并呈剂量依赖性。此外，CA以剂量依赖的方式减轻lps诱导的炎症反应。NC-WPMY-1和CA-WPMY-1显著提高RWPE-1细胞活力。我们还发现NC-WPMY-1-exo和CA-WPMY-1-exo都能逆转LPS对RWPE-1细胞活力、凋亡和炎症的影响。CA-WPMY-1-exo对RWPE-1细胞的影响较NC-WPMY-1-exo更为显著。结论ca暴露的前列腺基质细胞外泌体通过抑制lps诱导的上皮细胞炎症损伤而成为CP的重要介质。

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引用次数: 0

Pregnancy and Behçet Syndrome: A Large Retrospective Italian Study 妊娠和behaperet综合征：一项大型意大利回顾性研究

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2025-07-28 DOI: 10.1111/aji.70133

Pietro Leccese, Nancy Lascaro, Assunta Iuliano, Michele Gilio, Salvatore D'Angelo, Sergio C. A. Schettini, Angela Anna Padula, Maria Carmela Padula

Introduction

Behçet syndrome (BS) is a multifactorial disorder with several clinical manifestations that occurs during the childbearing age. The relationship between pregnancy and BS has been previously analysed as the pregnancy immunometabolic reprogramming in case of autoinflammatory and/or autoimmune diseases can influence both the course of the disease and the pregnancy outcomes. We aim to analyse the relationship between BS and pregnancy, investigating: (1) the prevalence and clinical characteristics of disease flares during pregnancy and (2) the pregnancy outcomes in a large cohort of Italian patients with BS.

Methods

This retrospective study was conducted recruiting a cohort of BS patients according to the criteria of the International Study Group for Behçet (ISG), following at the Rheumatology Department of Lucania (San Carlo Hospital, Potenza) from January 2000 to December 2021. We reviewed medical records and collected demographic and clinical data besides pregnancy-related data, in particular: maternal age, disease flares during and after pregnancy, post-partum maternal and neonatal complications (up to 6 months after pregnancy).

Results

We studied 153 pregnancies in 96/117 subjects (21/117 patients did not get pregnant). Three patients showed active disease (oral ulcers) at the time of conception. Disease flares were observed during gestation for 25/153 (16.3%) pregnancies, mainly mucocutaneous (oral and genital ulcers, erythema nodosum) and joint (arthralgia and arthritis) manifestations. A total of 27/153 (17.6%) cases of disease flares were observed after pregnancy, with mucocutaneous (oral and genital ulcers, erythema nodosum) and joint (arthralgia and arthritis) involvement, as well as anterior uveitis. Miscarriages, preterm delivery, pre-eclampsia and eclampsia were observed in 27/153 (17.6%), 19/153 (12.4%), 6/153 (3.9%) and 2/153 (1.3%) pregnancies, respectively. No cases of neonatal complications or death were observed.

Conclusions

The results of the present study underlined that: (a) BS disease clinical symptoms do not appear to worsen during pregnancy and (b) the pregnancy does not appear to be associated with increased gestational complications and adverse maternal-fetal outcomes in case of BS. However, due to the potential adverse events, especially of the vascular involvement, a strong multidisciplinary pregnancy follow-up is recommended.

behet综合征（BS）是一种多因素疾病，具有多种临床表现，发生在育龄期。妊娠与BS之间的关系先前已被分析，因为在自身炎症和/或自身免疫性疾病的情况下，妊娠免疫代谢重编程可以影响疾病的病程和妊娠结局。我们的目的是分析BS与妊娠之间的关系，调查：(1)妊娠期间疾病发作的患病率和临床特征；(2)意大利大队列BS患者的妊娠结局。方法本回顾性研究招募了一组BS患者，根据国际behet研究小组（ISG）的标准，于2000年1月至2021年12月在Lucania （San Carlo Hospital, Potenza）风湿病学系进行。我们审查了医疗记录，并收集了除妊娠相关数据外的人口统计和临床数据，特别是：产妇年龄、妊娠期间和妊娠后的疾病发作、产后产妇和新生儿并发症（妊娠后6个月）。结果153例妊娠，96/117例（21/117例未怀孕）。3例患者在受孕时出现活动性疾病（口腔溃疡）。153例妊娠中有25例（16.3%）在妊娠期间出现疾病发作，主要表现为皮肤粘膜（口腔和生殖器溃疡、结节性红斑）和关节（关节痛和关节炎）。153例中有27例（17.6%）在妊娠后出现疾病发作，伴有皮肤粘膜（口腔和生殖器溃疡、结节性红斑）和关节（关节痛和关节炎）受累，以及前葡萄膜炎。流产、早产、先兆子痫和子痫发生率分别为27/153（17.6%）、19/153（12.4%）、6/153（3.9%）和2/153（1.3%）。未观察到新生儿并发症或死亡病例。本研究的结果强调：(a) BS疾病的临床症状在妊娠期间似乎没有恶化，(b)妊娠似乎与BS的妊娠并发症增加和不良的母胎结局无关。然而，由于潜在的不良事件，特别是血管受累，建议进行强有力的多学科妊娠随访。

{"title":"Pregnancy and Behçet Syndrome: A Large Retrospective Italian Study","authors":"Pietro Leccese, Nancy Lascaro, Assunta Iuliano, Michele Gilio, Salvatore D'Angelo, Sergio C. A. Schettini, Angela Anna Padula, Maria Carmela Padula","doi":"10.1111/aji.70133","DOIUrl":"https://doi.org/10.1111/aji.70133","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Behçet syndrome (BS) is a multifactorial disorder with several clinical manifestations that occurs during the childbearing age. The relationship between pregnancy and BS has been previously analysed as the pregnancy immunometabolic reprogramming in case of autoinflammatory and/or autoimmune diseases can influence both the course of the disease and the pregnancy outcomes. We aim to analyse the relationship between BS and pregnancy, investigating: (1) the prevalence and clinical characteristics of disease flares during pregnancy and (2) the pregnancy outcomes in a large cohort of Italian patients with BS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study was conducted recruiting a cohort of BS patients according to the criteria of the International Study Group for Behçet (ISG), following at the Rheumatology Department of Lucania (San Carlo Hospital, Potenza) from January 2000 to December 2021. We reviewed medical records and collected demographic and clinical data besides pregnancy-related data, in particular: maternal age, disease flares during and after pregnancy, post-partum maternal and neonatal complications (up to 6 months after pregnancy).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We studied 153 pregnancies in 96/117 subjects (21/117 patients did not get pregnant). Three patients showed active disease (oral ulcers) at the time of conception. Disease flares were observed during gestation for 25/153 (16.3%) pregnancies, mainly mucocutaneous (oral and genital ulcers, erythema nodosum) and joint (arthralgia and arthritis) manifestations. A total of 27/153 (17.6%) cases of disease flares were observed after pregnancy, with mucocutaneous (oral and genital ulcers, erythema nodosum) and joint (arthralgia and arthritis) involvement, as well as anterior uveitis. Miscarriages, preterm delivery, pre-eclampsia and eclampsia were observed in 27/153 (17.6%), 19/153 (12.4%), 6/153 (3.9%) and 2/153 (1.3%) pregnancies, respectively. No cases of neonatal complications or death were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results of the present study underlined that: (a) BS disease clinical symptoms do not appear to worsen during pregnancy and (b) the pregnancy does not appear to be associated with increased gestational complications and adverse maternal-fetal outcomes in case of BS. However, due to the potential adverse events, especially of the vascular involvement, a strong multidisciplinary pregnancy follow-up is recommended.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714866","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}

引用次数: 0

Comparative Analysis of Immune Cell Populations From Two Sampling Techniques of Human Term Decidua Utilizing High-Parameter Full-Spectrum Flow Cytometry 利用高参数全谱流式细胞术对两种人足月蜕膜取样技术免疫细胞群的比较分析

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2025-07-23 DOI: 10.1111/aji.70130

Abigail L. P. Spray, Shahrokh Paktinat, Cara Tobey, Maryam Kalatehjari, Nolawit M. Mulugeta, Michelle Asencio, Sam Rosen, Michael G. Gravett, Lucia Vojtech, Stephen A. McCartney

Problem

The decidua is the interface between the uterus and the fetus. Studying decidual cells can reveal how healthy pregnancies are supported and mechanisms of pregnancy complications. There are two methods of obtaining decidual tissue following delivery. The placental bed can be suctioned following C-section deliveries, or a thin layer of decidual tissue can be dissected from the placenta. This study aimed to compare immune cell populations obtained using the two methods.

Method of Study

From individuals with scheduled C-sections, we collected peripheral blood, decidua via vacuum suction of the placental bed, and decidua via dissection of the uterine-facing side of the placenta. Samples were analyzed using a 22-color full-spectrum flow cytometry panel to identify immune cell subsets and functional markers.

Results

The cellular composition of both decidual tissue collection methods were more similar to each other than to peripheral blood. Decidua collected via vacuum suction (Suc. decidua) had more live CD45+ cells. Decidua collected via dissection of the uterine-facing side of the placenta (Plac. decidua) had significantly higher expression of Helios in CD4+ cells, suggesting more fetal T cells. Both types of decidual samples contained similar levels of Tr1-like regulatory T lymphocytes expressing LAG3 and CD49b, whereas peripheral blood did not have this cell type.

Conclusion

Collecting decidual tissue using either method resulted in largely similar immune cell populations, suggesting studies are largely comparable regardless of whether samples were collected via suction or placental dissection. This will allow for greater flexibility in sample collection methods.

蜕膜是子宫和胎儿之间的界面。研究蜕细胞可以揭示健康妊娠是如何得到支持的以及妊娠并发症的机制。分娩后获得蜕膜组织有两种方法。剖宫产后，可抽吸胎盘床，或从胎盘上剥离一层薄薄的蜕膜组织。这项研究旨在比较使用这两种方法获得的免疫细胞群。研究方法：我们收集了预定剖腹产患者的外周血，通过胎盘床的真空吸取蜕膜，并通过剥离胎盘面向子宫一侧的蜕膜。使用22色全光谱流式细胞仪分析样品以鉴定免疫细胞亚群和功能标记物。结果两种标本的细胞组成与外周血的细胞组成更相似。真空抽吸收集蜕膜(如：蜕膜)有更多的活CD45+细胞。剖开胎盘面向子宫一侧收集蜕膜。Helios在CD4+细胞中的表达明显增高，提示胎儿有更多的T细胞。两种类型的蜕膜样本含有相似水平的表达LAG3和CD49b的tr1样调节性T淋巴细胞，而外周血没有这种细胞类型。结论两种方法采集的蜕膜组织免疫细胞群基本相似，提示无论样本是通过吸力采集还是胎盘剥离采集，研究在很大程度上具有可比性。这将使样品收集方法具有更大的灵活性。

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引用次数: 0

Macrophage Switching in Pregnancy: Regulatory Mechanisms Governing Term Labour and Preterm Birth 巨噬细胞在妊娠中的转换：足月分娩和早产的调节机制

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2025-07-18 DOI: 10.1111/aji.70123

G. Ravi Prakash, Ayushi Vaidhya, V. Deepthi, Laxmi Singh Rathore, Manjit Panigrahi, C. L. Madhu, T. U. Singh, Subhashree Parida

Macrophages play a pivotal role in the immune adaptations required for pregnancy, influencing both term and preterm labour (PTL) through their activation and polarisation. These immune cells originate from the yolk sac, foetal liver, and bone marrow, differentiating into diverse subtypes, including pro-inflammatory (M1) and anti-inflammatory (M2) macrophages. The dynamic transition between these states, termed macrophage switching, is crucial for maintaining pregnancy and orchestrating labour. This switch is tightly regulated by hormones, cytokines and immune signals, ensuring a controlled inflammatory response at term whilst preventing pathological inflammation leading to preterm birth. During term labour, macrophages accumulate in the cervix, decidua and myometrium, responding to signals from placental aging, foetal lung maturation and endocrine changes. They secrete pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), matrix metalloproteinases (MMPs) and prostaglandins, promoting uterine contractions and cervical remodelling. The sources of these macrophages include maternal monocytes recruited from circulation and resident decidual macrophages (DMs). In contrast, PTL often arises from dysregulated macrophage activation due to infection, sterile inflammation, or stress signals, triggering an early pro-inflammatory shift. Premature M1 dominance leads to excessive inflammation, extracellular matrix degradation and foetal membrane rupture. Understanding the mechanisms regulating macrophage switching in PTL, including TLR signalling and hormonal modulation, may uncover therapeutic targets and suitable interventions. This review explores the origins, activation, and functional switching of macrophages in term and preterm labor, emphasising their regulatory mechanisms and potential interventions to prevent preterm birth.

巨噬细胞在妊娠所需的免疫适应中发挥关键作用，通过其激活和极化影响足月和早产（PTL）。这些免疫细胞来源于卵黄囊、胎儿肝脏和骨髓，分化成不同的亚型，包括促炎（M1）和抗炎（M2）巨噬细胞。这些状态之间的动态转换，称为巨噬细胞转换，对维持妊娠和协调分娩至关重要。这种开关受到激素、细胞因子和免疫信号的严格调节，确保在足月时控制炎症反应，同时防止病理性炎症导致早产。在足月分娩期间，巨噬细胞在子宫颈、蜕膜和子宫肌层聚集，响应胎盘老化、胎儿肺成熟和内分泌变化的信号。它们分泌促炎细胞因子（TNF-α、IL-1β和IL-6）、基质金属蛋白酶（MMPs）和前列腺素，促进子宫收缩和宫颈重塑。这些巨噬细胞的来源包括从循环中募集的母体单核细胞和常驻的巨噬细胞（DMs）。相反，PTL通常是由感染、无菌炎症或应激信号引起的巨噬细胞激活失调引起的，从而引发早期的促炎转移。过早的M1优势导致过度炎症，细胞外基质降解和胎膜破裂。了解巨噬细胞在PTL中转换的调节机制，包括TLR信号和激素调节，可能会发现治疗靶点和合适的干预措施。本文综述了巨噬细胞在足月和早产中的起源、激活和功能转换，重点介绍了巨噬细胞的调节机制和预防早产的潜在干预措施。

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引用次数: 0

Evaluation of Th1-Th2 Balance in Patients With Unexplained Recurrent Spontaneous Abortion: A Systematic Review and Meta-Analysis 不明原因复发性自然流产患者Th1-Th2平衡的评价：一项系统综述和荟萃分析

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2025-07-12 DOI: 10.1111/aji.70125

Reza Kargar, Zahra Yahoo, Hosein Rafiemanesh, Saeed Aslani, Atefeh Shamosi, Hamed Mohammadi

Objective

Unexplained recurrent spontaneous abortion (URSA) poses a major challenge in reproductive medicine, with increasing evidence of maternal immune dysregulation. This systematic review and meta-analysis assessed differences in T helper (Th) 1 and Th2 cell frequencies and their ratio between women with URSA and healthy fertile controls.

Methods

A comprehensive search of PubMed, Scopus, and Web of Science (WoS), up to October 2024, included studies evaluating peripheral blood Th subsets by flow cytometry.

Results

Meta-analyses were performed for Th1(IFN-γ), Th1(TNF-α), Th2(IL-4), Th2(IL-10), and Th1/Th2 ratios. Th1(IFN-γ) frequencies were significantly higher in URSA (mean difference [MD] = 2.31, 95% CI = 0.30–4.33, p = 0.02), while Th2(IL-4) levels were lower (MD = −0.51, 95% CI = −0.91 to −0.11, p = 0.01). No significant differences were observed for Th1(TNF-α) (SMD = 0.25, 95% CI = −0.06 to 0.55, p = 0.11) and Th2(IL-10) (SMD = −0.28, 95% CI = −0.62 to 0.05, p = 0.10). The Th1(IFN-γ)/Th2(IL-4) ratio was significantly elevated (MD = 5.37, 95% CI = 1.47–9.27, p = 0.007), reflecting a shift toward a Th1-dominant immune profile.

Conclusions

These findings support the role of Th1/Th2 imbalance in URSA and suggest its potential value as a diagnostic or prognostic marker.

目的不明原因复发性自然流产（URSA）是生殖医学面临的重大挑战，越来越多的证据表明，母体免疫失调。本系统综述和荟萃分析评估了辅助性T细胞（Th） 1和Th2细胞频率及其在URSA女性和健康生育对照组之间的差异。方法综合检索截至2024年10月的PubMed、Scopus和Web of Science (WoS)，包括用流式细胞术评估外周血Th亚群的研究。结果对Th1（IFN-γ）、Th1（TNF-α）、Th2（IL-4）、Th2（IL-10）和Th1/Th2比值进行meta分析。URSA患者中Th1（IFN-γ）频率显著升高（平均差异[MD] = 2.31, 95% CI = 0.30 ~ 4.33, p = 0.02）， Th2（IL-4）水平显著降低（MD = - 0.51, 95% CI = - 0.91 ~ - 0.11, p = 0.01）。Th1(TNF-α) （SMD = 0.25, 95% CI = - 0.06 ~ 0.55, p = 0.11）和Th2(IL-10) （SMD = - 0.28, 95% CI = - 0.62 ~ 0.05, p = 0.10）无显著差异。Th1(IFN-γ)/Th2（IL-4）比值显著升高（MD = 5.37, 95% CI = 1.47-9.27, p = 0.007），反映了向Th1显性免疫谱的转变。结论这些发现支持Th1/Th2失衡在URSA中的作用，并提示其作为诊断或预后指标的潜在价值。

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引用次数: 0

Salvianolic Acid B Promotes Placental and Decidual Angiogenesis by Restoring the Normal Expression of Hypoxia-Inducible Factor-1α/Vascular Endothelial Growth Factor in Mice With Recurrent Pregnancy Loss 丹酚酸B通过恢复缺氧诱导因子-1α/血管内皮生长因子的正常表达促进胎盘和蜕膜血管生成

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2025-07-10 DOI: 10.1111/aji.70105

Fangfang Hu, Chao Yang, Lujun Dai, Dan Gao, Heng Luo, Xingming Zhong, Panpan Chen, Leilei Zhu, Ziwen Xiao, Shuyun Zhao, Guanyou Huang

<div> <section> <h3> Introduction</h3> <p>Accumulating evidence suggests the association between abnormal angiogenesis at the maternal–fetal interface and recurrent pregnancy loss (RPL); nonetheless, the mechanism remains largely unknown. Previous studies have reported the clinical effect of the traditional Chinese medicine Danshen in the treatment of RPL. This study aimed to investigate whether salvianolic acid B (SalB), the primary water-soluble component of Danshen, could reduce the embryonic absorption rate (EAR) by increasing placental and decidual angiogenesis in RPL mice and to explore the possible mechanism.</p> </section> <section> <h3> Methods</h3> <p>The decidual and chorionic tissues were collected from normal pregnancies and unknown recurrent pregnancy loss (URPL) patients. Western blotting was used to determine the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) in the tissues. Different doses of SalB and/or the VEGF inhibitor PTC299 were intragastrically administered to normal and RPL pregnant mice daily at 0.5 day of pregnancy for 10 days. The EAR, mean placental weight (MPW), and micro vessel density (MVD) were determined in placental and decidual tissues, and the number of live pups per litter was counted. The expression of VEGF and HIF-1α in the tissues was evaluated using western blotting and immunohistochemistry.</p> </section> <section> <h3> Results</h3> <p>The VEGF protein levels in decidual and chorionic tissues were significantly lower, and HIF-1α levels were significantly higher than that of normal pregnancies. The EAR was significantly higher, MVD, MPW, and protein levels of VEGF in the placental and decidual tissues of RPL mice were significantly lower than those in normal mice. In contrast, the protein levels of HIF-1α were significantly higher in RPL mice than in normal mice. SalB restored the morphological changes in the uterus of RPL mice, as well as the number of blood vessels in the placenta and decidua, and ameliorated adverse embryonic development in mice (such as neural tube defects and reduced crown-rump length), thereby increasing the pups per. Additionally, SalB increased the VEGF/VEGFR2/p-VEGFR2 levels, placental and decidual MVD, and MPW and decreased the HIF-1α levels and EAR in a dose-dependent manner. A positive association of daily SalB dose (0–100 mg/kg) with the VEGF levels, placental and decidual MVD and MPW, and a negative association of daily SalB dose with the HIF-1α levels and EAR were observed.PTC299 reversed the aforementioned increases and decreases in the daily SalB intake of RPL mice. Among these, the daily dose of 100 mg/kg of SalB was deemed optimal, and a daily dose of SalB exceeding 100 mg/kg did not

越来越多的证据表明，母胎界面异常血管生成与复发性妊娠丢失（RPL）之间存在关联；尽管如此，其机制在很大程度上仍然未知。以往的研究报道了中药丹参治疗RPL的临床疗效。本研究旨在探讨丹参主要水溶性成分丹酚酸B （SalB）是否能通过促进RPL小鼠胎盘和蜕膜血管生成来降低胚胎吸收率（EAR），并探讨其可能的机制。方法收集正常妊娠和不明原因复发性妊娠丢失（URPL）患者的蜕膜和绒毛膜组织。Western blotting检测组织中血管内皮生长因子（VEGF）和缺氧诱导因子-1α (HIF-1α)的表达。不同剂量的SalB和/或VEGF抑制剂PTC299在妊娠0.5天每天灌胃给正常和RPL妊娠小鼠，持续10天。测定各组胎盘和蜕膜组织的EAR、平均胎盘重（MPW）和微血管密度（MVD），并统计每窝活仔数。采用western blotting和免疫组织化学检测各组组织中VEGF和HIF-1α的表达。结果胎鼠蜕膜和绒毛膜组织中VEGF蛋白水平明显低于正常妊娠组，HIF-1α水平明显高于正常妊娠组。RPL小鼠的EAR显著升高，胎盘和蜕膜组织中MVD、MPW和VEGF蛋白水平显著低于正常小鼠。相比之下，RPL小鼠的HIF-1α蛋白水平明显高于正常小鼠。SalB恢复了RPL小鼠子宫的形态变化，以及胎盘和蜕膜中的血管数量，改善了小鼠胚胎发育不良（如神经管缺陷和冠臀长度减少），从而提高了幼崽数。此外，SalB增加了VEGF/VEGFR2/p-VEGFR2水平、胎盘和蜕膜MVD和MPW，并以剂量依赖的方式降低了HIF-1α水平和EAR。每日SalB剂量（0 ~ 100 mg/kg）与VEGF水平、胎盘和蜕膜MVD和MPW呈正相关，与HIF-1α水平和EAR呈负相关。PTC299逆转了上述RPL小鼠每日SalB摄入量的增加和减少。其中，100 mg/kg的SalB日剂量被认为是最佳的，超过100 mg/kg的SalB日剂量并不能完全诱导这些变化。在正常妊娠和URPL患者以及正常和RPL小鼠的蜕膜和胎盘/绒毛膜组织中未观察到HIF-1α和VEGF之间的相关性，但在存在或不存在PTC299的SalB的RPL小鼠组织中观察到两者之间的负相关。结论SalB通过恢复HIF-1α/VEGF的生理性平衡和胎盘血管生成来改善RPL。最佳日剂量为100 mg/kg，显示无胚胎毒性或减轻RPL小鼠的胚胎毒性，而更高剂量（400 mg/kg）表现出较小的改善和增加的肝毒性。促进胎盘和蜕膜血管生成可能是治疗不明原因RPL的有效策略。

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引用次数: 0

Prediction of Delivery Timing in Preterm Premature Rupture of Membranes: The Role of Inflammation-Related Indices 预测早产胎膜早破的分娩时间：炎症相关指标的作用

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2025-07-10 DOI: 10.1111/aji.70124

Merve Ayas Ozkan, Zeynep Seyhanlı, Seval Yılmaz Ergani, Kadriye Yakut Yücel

Objective

The aim of this study was to evaluate the predictivevalue of inflammatory parameters platelet-albumin ratio (PAR), systemic immune-inflammation index (SII), and multi-inflammatory indices (MII) in forecasting the timing of delivery in pregnancies diagnosed with preterm premature rupture of membranes (PPROM).

Materials and Methods

A retrospective analysis was conducted on 292 pregnant women diagnosed with PPROM between 24 and 34 gestational weeks at Etlik City Hospital from January 2023 to December 2024. The patients were grouped according to their time of delivery: those delivering within 48, 72, and 96 h. Inflammatory indices, including PAR, SII, MII-1, and MII-2 were calculated using complete blood count and biochemical parameters obtained at admission, and their predictive performance for delivery timing was assessed using receiver operating characteristic (ROC) analysis.

Results

For predicting delivery within 48 h, the AUC (areas under the curve) values were 0.566 for PAR (p = 0.050), 0.575 for SII (p = 0.027), and 0.567 for MII-1 (p = 0.046). For predicting delivery within 72 h, the AUC values were 0.603 for SII (p = 0.003), 0.591 for MII-1 (p = 0.008), and 0.584 for MII-2 (p = 0.015), indicating a moderate level of predictive value. For predicting delivery within 96 h, SII (AUC = 0.627, p < 0.001) and MII-1 (AUC = 0.617, p = 0.001) demonstrated the highest predictive power.

Conclusion

PAR, SII, and MII-1/2 may assist in predicting the timing of delivery in PPROM cases. However, prospective multicenter studies with larger patient cohorts are needed before these parameters can be routinely implemented in clinical practice.

目的探讨血小板-白蛋白比（PAR）、全身免疫-炎症指数（SII）和多炎症指数（MII）对诊断为胎膜早破（PPROM）的妊娠分娩时间的预测价值。材料与方法回顾性分析2023年1月至2024年12月在Etlik市医院就诊的292例24 ~ 34孕周PPROM孕妇。根据分娩时间对患者进行分组：48小时、72小时和96小时内分娩的患者。使用入院时获得的全血细胞计数和生化参数计算炎症指标，包括PAR、SII、MII-1和MII-2，并使用受试者工作特征（ROC）分析评估其对分娩时间的预测性能。结果预测48 h内分娩，PAR的AUC（曲线下面积）为0.566 (p = 0.050)， SII的AUC为0.575 (p = 0.027)， MII-1的AUC为0.567 （p = 0.046）。对于72h内分娩的预测，SII的AUC值为0.603 (p = 0.003)， MII-1的AUC值为0.591 (p = 0.008)， MII-2的AUC值为0.584 (p = 0.015)，表明预测价值中等。预测96小时内分娩，SII (AUC = 0.627, p <；0.001)和MII-1 （AUC = 0.617, p = 0.001）表现出最高的预测能力。结论PAR、SII和MII-1/2有助于预测PPROM患者的分娩时间。然而，在这些参数常规应用于临床实践之前，需要有更大患者队列的前瞻性多中心研究。

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引用次数: 0

Association of Periconceptional Dietary Inflammatory Index and Hypertensive Disorders of Pregnancy and Its Subtype 围孕期饮食炎症指数与妊娠高血压疾病及其亚型的关系

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2025-07-08 DOI: 10.1111/aji.70122

McKenzie K. Jancsura, Nathan P. Helsabeck, Michael D. Wirth, Hanna Griffis, Tamera Hatfield, Elizabeth A. Ferries-Rowe, Uma M. Reedy, Hyagriv Simhan, Lynn Yee, Robert M. Silver, Kartik K. Venkatesh, William A. Grobman

Background

The association between diet and hypertensive disorders of pregnancy (HDP) is inconclusive due incomplete assessment of dietary measures and HDP subtypes.

Objective

We determined the association between the energy-adjusted Dietary Inflammatory Index (E-DII) and the risk of HDP subtypes in a large, diverse cohort of pregnant individuals.

Methods

We completed a secondary analysis of data from the nuMoM2b study. Participants (n = 7309) were recruited from eight sites across the United States in the first trimester and followed through delivery. Participants completed the Block Food Frequency Questionnaire during the first trimester, which assessed the periconceptional period. Calculated macro and micronutrients from the questionnaire were used to calculate E-DII scores. HDP subtypes included gestational hypertension, preeclampsia without severe features, and preeclampsia with severe features. Multivariable ordinal logistic regression models were used to assess the association between E-DII and HDP subtypes, adjusting for baseline age, body mass index, education, race, and ethnicity as a social construct, and insurance status.

Results

Among 7309 assessed individuals, the mean E-DII score was −0.61, and the frequency of gestational hypertension was 15.5%, preeclampsia without severe features was 4.3%, and preeclampsia with severe features was 4.1%. A higher E-DII score was associated with greater odds of developing an HDP, with worsening E-DII scores associated with greater odds of experiencing a more severe HDP subtype (adjusted OR = 1.15, 95% CI: 1.08, 1.22).

Conclusions

In a multisite prospective US cohort of nulliparous individuals, higher periconceptional E-DII scores indicative of a pro-inflammatory diet was associated with a slightly increased risk of HDP. And the severity of HDP progressively increased with worsening dietary inflammation.

饮食与妊娠期高血压疾病（HDP）之间的关系尚不确定，因为对饮食措施和HDP亚型的评估不完整。目的：在一个大型、多样化的孕妇队列中，我们确定能量调节饮食炎症指数（E-DII）与HDP亚型风险之间的关系。我们完成了对nuMoM2b研究数据的二次分析。参与者（n = 7309）在怀孕的前三个月从美国八个地点招募，并随访到分娩。参与者在怀孕的前三个月完成了“块状食物频率问卷”，以评估围孕期。从问卷中计算出的宏量营养素和微量营养素用于计算E-DII分数。HDP亚型包括妊娠期高血压、无严重特征的先兆子痫和有严重特征的先兆子痫。多变量有序逻辑回归模型用于评估E-DII和HDP亚型之间的关系，调整基线年龄、体重指数、教育程度、种族和民族作为社会结构和保险状况。结果7309例患者E-DII平均评分为- 0.61，妊娠期高血压发生率为15.5%，无严重特征子痫前期发生率为4.3%，有严重特征子痫前期发生率为4.1%。E-DII评分越高，发生HDP的几率越大，E-DII评分越差，发生更严重HDP亚型的几率越大（调整后OR = 1.15, 95% CI: 1.08, 1.22）。结论：在美国一项针对未生育个体的多地点前瞻性队列研究中，较高的孕产期E-DII评分表明促炎饮食与HDP风险略有增加相关。随着饮食炎症的加重，HDP的严重程度逐渐增加。

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引用次数: 0