Journal of Reproductive Immunology最新文献_第3页

The efficacy of immunotherapies for pregnancy outcomes of patients with recurrent implantation failure as defined by ESHRE guidelines: A systematic review and network meta-analysis 免疫疗法对ESHRE指南定义的复发性植入失败患者妊娠结局的疗效：系统回顾和网络荟萃分析

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2026-01-08 DOI: 10.1016/j.jri.2025.104825

Ying Li , Peixuan Lan , Jing Tang , Wenjun Wang , Hui Chen

This study aimed to evaluate the efficacy of immunotherapies for recurrent implantation failure (RIF), as newly defined by ESHRE 2023. We conducted network meta-analyses of randomized trials on immunomodulatory therapies for well-defined RIF from PubMed, Embase, Web of Science, and Cochrane Library up to October 2024. We assessed clinical outcomes, including clinical pregnancy rate (CPR), live birth rate (LBR), implantation rate (IR), and miscarriage rate (MR), using odds ratios (OR) and 95 % confidence-intervals (CI). Statistical analysis was performed with STATA. Nineteen trials involving 2434 women were included, comparing nine immunotherapies. Compared to controls, low-molecular-weight heparin (LMWH) (OR 4.05, 95 %CI 1.78–9.24, surface under the cumulative ranking curve (SUCRA) 77.1 %) and platelet-rich plasma (PRP) (OR 3.27, 95 %CI 1.42–7.52, SUCRA 66.5 %) significantly improve IR, while sirolimus (OR 3.95, 95 %CI 1.46–10.71, SUCRA 81.9 %) and PRP (OR 3.45, 95 %CI 2.45–4.85, SUCRA 80.3 %) notably increased CPR. Subcutaneous granulocyte colony-stimulating factor (SC-GCSF) (OR 9.00, 95 %CI 1.42–57.12, SUCRA 93.7 %) were associated with higher LBR. LMWH (OR 0.12, 95 %CI 0.02–0.80, SUCRA 84.6 %) and PRP reduced MR (OR 0.15, 95 %CI 0.04–0.50, SUCRA 82.2 %). Subgroup analysis indicated that a 0.5 ml intrauterine PRP dose 48 h before embryo transfer (ET) enhanced CPR (OR 3.96, 95 %CI 2.74–5.74) and reduced MR (OR 0.10, 95 %CI 0.04–0.22). In newly defined RIF patients, sirolimus and PRP effectively enhance CPR, while SC-GCSF optimizes LBR. LMWH is most effective for improving IR and reducing MR. PRP, particularly with a single 0.5 ml intrauterine dose, optimally increases CPR and reduces MR. Intrauterine G-CSF showed no significant benefits.

Trial Registration

The protocol was registered on OSF: https://doi.org/10.17605/OSF.IO/GVEP9.

本研究旨在评估免疫疗法治疗复发性植入失败（RIF）的疗效，RIF是ESHRE 2023新定义的。截至2024年10月，我们对PubMed、Embase、Web of Science和Cochrane Library中明确定义的RIF的免疫调节疗法的随机试验进行了网络荟萃分析。我们评估临床结果，包括临床妊娠率（CPR）、活产率（LBR）、着床率（IR）和流产率（MR），使用优势比（OR）和95% %置信区间（CI）。采用STATA进行统计分析。纳入了19项试验，涉及2434名妇女，比较了9种免疫疗法。与对照组相比，低分子肝素（LMWH）（OR 4.05, 95 %CI 1.78-9.24，累积排名曲线下表面（SUCRA） 77.1 %）和富血小板血浆（PRP）（OR 3.27, 95 %CI 1.42-7.52, SUCRA 66.5 %）显著改善IR，而西罗莫司（OR 3.95, 95 %CI 1.46-10.71, SUCRA 81.9 %）和PRP （OR 3.45, 95 %CI 2.45-4.85, SUCRA 80.3 %）显著提高CPR。皮下粒细胞集落刺激因子（SC-GCSF）（OR 9.00, 95 %CI 1.42-57.12, SUCRA 93.7 %）与较高的LBR相关。低分子肝素（OR 0.12, 95 %CI 0.02-0.80, SUCRA 84.6 %）和PRP降低MR （OR 0.15, 95 %CI 0.04-0.50, SUCRA 82.2 %）。亚组分析显示，胚胎移植（ET）前48 h， 0.5 ml宫内PRP剂量可增强CPR (OR 3.96, 95 %CI 2.74-5.74)，降低MR （OR 0.10, 95 %CI 0.04-0.22）。在新定义的RIF患者中，西罗莫司和PRP可有效增强CPR，而SC-GCSF可优化LBR。低分子肝素对改善IR和降低MR. PRP最有效，特别是单次0.5 ml宫内剂量，最佳地增加CPR和降低MR.宫内G-CSF没有显着的益处。试验注册本协议在OSF上注册：https://doi.org/10.17605/OSF.IO/GVEP9。

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引用次数: 0

Immuno-metabolic dysregulation in female genital tuberculosis: Multi-omics insights into infertility mechanisms and therapeutic targets 女性生殖器结核的免疫代谢失调：不孕机制和治疗靶点的多组学见解。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2026-01-05 DOI: 10.1016/j.jri.2026.104833

Guiyi Ji , Yunxing Fu , Linlin Song , Rong Hu

Female genital tuberculosis (FGTB) is a major cause of infertility in regions where it is common, causing permanent damage to the reproductive tract. It mainly causes fibrosis and blockage of the fallopian tubes, directly hindering gamete movement. Meanwhile, FGTB leads to a decline in ovarian reserve and function by disrupting folliculogenesis in the ovaries, resulting in decreased levels of anti-Müllerian hormone (AMH). Mycobacterium tuberculosis also affects endometrial receptivity by inhibiting the STAT3/VEGF pathway and the imbalance of Th1/Th2 immune responses. This review explains these mechanisms and offers a multi-omics approach for early detection, identifying taurine deficiency in endometrial fluid and the TLR8 rs3764880 polymorphism as potential predictive markers. Importantly, we point out that first-line anti-tuberculosis therapy (ATT) may worsen ovarian damage by causing mitochondrial dysfunction in oocytes. For treatment, we propose the TB-FertiScore to assist personalized management: patients with a high risk (score ≥7) and severe tubo-ovarian damage should receive ATT combined with IVF, while those with less severe disease might benefit from ovulation induction along with intrauterine VEGF treatment. This comprehensive approach allows for precise, risk-based fertility preservation in areas heavily affected by the disease.

女性生殖器结核病（FGTB）是常见地区不孕不育的一个主要原因，对生殖道造成永久性损害。它主要引起输卵管纤维化和阻塞，直接阻碍配子运动。同时，FGTB通过破坏卵巢卵泡生成导致卵巢储备和功能下降，导致抗勒氏激素（AMH）水平下降。结核分枝杆菌还通过抑制STAT3/VEGF通路和Th1/Th2免疫反应失衡影响子宫内膜容受性。这篇综述解释了这些机制，并提供了早期检测的多组学方法，确定子宫内膜液中牛磺酸缺乏和TLR8 rs3764880多态性作为潜在的预测标志物。重要的是，我们指出一线抗结核治疗（ATT）可能通过引起卵母细胞线粒体功能障碍加重卵巢损伤。对于治疗，我们建议TB-FertiScore来协助个性化管理：高风险（评分≥7）和严重输卵管卵巢损伤的患者应接受ATT联合IVF，而病情较轻的患者可能受益于促排卵和宫内VEGF治疗。这种综合方法可以在受该病严重影响的地区精确地、基于风险的保留生育能力。

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引用次数: 0

The role of extracellular vesicles in animal reproduction 细胞外囊泡在动物生殖中的作用。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2026-01-03 DOI: 10.1016/j.jri.2025.104831

Asal Golchin , Amirhossein Faghih Ojaroodi , Siamak Rezaeiani , Hojat Ghasemnejad-Berenji , Mortaza Taheri-Anganeh

Infertility affects approximately one in six couples worldwide and remains a multifactorial condition influenced by genetic, physiological, and environmental factors. Despite remarkable advances in assisted reproductive technologies (ART), current therapeutic approaches often fail to address the underlying molecular mechanisms contributing to infertility. In recent years, extracellular vesicles (EVs) have emerged as key mediators of intercellular communication, capable of transferring bioactive molecules such as proteins, lipids, and nucleic acids between cells within the reproductive system. Evidence indicates that EVs derived from reproductive tissues—including the testis, epididymis, uterus, and oviduct—play essential roles in gametogenesis, fertilization, embryogenesis, and implantation by modulating gene expression and cellular signaling in recipient cells. Studies have demonstrated that epididymal EVs regulate sperm maturation and motility, while uterine and oviductal EVs enhance sperm function and embryo development. Furthermore, the ability to engineer EVs for therapeutic delivery offers a promising strategy to improve gamete and embryo quality, mitigate implantation failure, and enhance ART outcomes. Veterinary research has further underscored the potential of EVs in cryopreservation, oocyte maturation, and management of reproductive disorders across species. Nonetheless, challenges remain regarding standardization of isolation techniques, elucidation of molecular cargo, and understanding the mechanisms of EV-mediated effects. Future research integrating advanced omics, microfluidics, and bioengineering technologies may unlock the full clinical potential of EVs as diagnostic biomarkers and therapeutic agents in reproductive medicine.

全世界大约六分之一的夫妇患有不孕症，这是一种受遗传、生理和环境因素影响的多因素疾病。尽管辅助生殖技术（ART）取得了显著进步，但目前的治疗方法往往无法解决导致不孕症的潜在分子机制。近年来，细胞外囊泡（EVs）作为细胞间通讯的关键媒介，能够在生殖系统内的细胞间传递生物活性分子，如蛋白质、脂质和核酸。有证据表明，来自生殖组织（包括睾丸、附睾、子宫和输卵管）的ev通过调节受体细胞的基因表达和细胞信号传导，在配子体发生、受精、胚胎发生和着床中发挥重要作用。研究表明，附睾EVs调节精子的成熟和运动，而子宫和输卵管EVs促进精子功能和胚胎发育。此外，设计ev用于治疗递送的能力为改善配子和胚胎质量、减轻植入失败和提高ART结果提供了一个有希望的策略。兽医研究进一步强调了ev在超低温保存、卵母细胞成熟和跨物种生殖障碍管理方面的潜力。尽管如此，在分离技术的标准化、分子货物的阐明以及了解ev介导效应的机制方面，挑战仍然存在。结合先进的组学、微流体和生物工程技术，未来的研究可能会释放电动汽车作为生殖医学诊断生物标志物和治疗药物的全部临床潜力。

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引用次数: 0

Recent research progress on pathophysiological mechanism and clinical treatment of recurrent spontaneous abortion and prethrombotic state 复发性自然流产及血栓前状态的病理生理机制及临床治疗研究进展。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2026-01-02 DOI: 10.1016/j.jri.2025.104822

Wei Zheng , Lingxia Zhang , Jie Ning , Sanzheng Yuan , Mengyang Song , Wei Li , Huijun Xu , Shuang Wang

Recurrent spontaneous abortion (RSA) refers to three or more consecutive spontaneous abortions before the 20th week of gestation. According to the research data of World Health Organization, worldwide, RSA has affected about 1–5 % of women of childbearing age, bringing great physical damage and psychological pressure to patients. The etiology of RSA is very complex, involving genetic factors (couples chromosome abnormalities or embryo chromosome abnormalities), physiological and structural factors (uterine congenital malformations, etc.), endocrine disorders, immune system abnormalities and prethrombotic state and many other factors. In recent years, Prethrombotic state (PTS) has been considered as one of the important causes of RSA, which is characterized by hypercoagulation, defects of anticoagulant mechanism or reduced fibrinolytic activity, leading to placental microcirculation dysfunction, and further leading to abortion. However, although RSA and PTS have been extensively studied by many researchers, the association between PTS and RSA is still not clear. This paper reviews the pathophysiological mechanism between PTS and RSA, as well as the early screening and diagnosis of PTS, and summarizes the clinical treatment of RSA related to PTS, in order to provide a solid theoretical basis for the follow-up treatment of RSA related to PTS.

复发性自然流产（RSA）是指妊娠20周前连续三次及以上的自然流产。根据世界卫生组织的研究数据，在世界范围内，RSA影响了约1- 5% 的育龄妇女，给患者带来了巨大的身体伤害和心理压力。RSA的病因非常复杂，涉及遗传因素（夫妻染色体异常或胚胎染色体异常）、生理结构因素（子宫先天性畸形等）、内分泌紊乱、免疫系统异常及血栓前状态等诸多因素。近年来，血栓前状态（Prethrombotic state， PTS）被认为是RSA发生的重要原因之一，其特征为高凝、抗凝机制缺陷或纤溶活性降低，导致胎盘微循环功能障碍，进而导致流产。然而，尽管RSA和PTS已被许多研究者广泛研究，但PTS与RSA之间的关系尚不清楚。本文综述了PTS与RSA之间的病理生理机制，以及PTS的早期筛查和诊断，并总结了PTS相关RSA的临床治疗，以期为PTS相关RSA的后续治疗提供坚实的理论基础。

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引用次数: 0

Exploratory evaluation of the bacterial load of uterine microbiota: Potential implications for implantation and treatment response in assisted reproductive technology 子宫微生物群细菌负荷的探索性评估：对辅助生殖技术植入和治疗反应的潜在影响。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-12-31 DOI: 10.1016/j.jri.2025.104830

Daisuke Kadogami , Yoshiharu Nakaoka , Yoshiharu Morimoto

The clinical impact of endometrial microbiota on assisted reproductive technology (ART) primarily relates to the supremacy of Lactobacillus and its species composition. However, bacterial load, reflecting total microbial biomass, may be another key parameter influencing ART outcomes. This study aimed to evaluate whether bacterial load is a useful metric for assessing the endometrial environment and predicting ART success. This retrospective study included 223 women with recurrent implantation failure (RIF). Endometrial samples were collected and analyzed using 16S rRNA gene sequencing to determine microbiota composition and Lactobacillus abundance. The bacterial load was quantified via qPCR. Patients were categorized as Lactobacillus-dominant (LD) or non-Lactobacillus-dominant (NLD). We assessed the associations between bacterial load, implantation, pregnancy outcomes, and therapeutic response in NLD. Additionally, the optimal bacterial load range and related host factors were evaluated. A higher bacterial load was associated with LD status and a better treatment response in NLD. Although implantation and ongoing pregnancy rates were not significantly correlated with bacterial load, a potential link with pregnancy outcome was observed. Body mass index (BMI) and age were not associated with bacterial load variability. In conclusion, a quantitative assessment of bacterial load may complement microbiota composition analysis in evaluating endometrial environments for ART.

子宫内膜微生物群对辅助生殖技术（ART）的临床影响主要与乳酸菌及其物种组成的优势有关。然而，反映总微生物生物量的细菌负荷可能是影响抗逆转录病毒治疗结果的另一个关键参数。本研究旨在评估细菌负荷是否是评估子宫内膜环境和预测ART成功的有用指标。这项回顾性研究包括223名复发性植入失败（RIF）的妇女。收集子宫内膜样品，采用16S rRNA基因测序分析微生物群组成和乳酸菌丰度。通过qPCR定量细菌载量。患者分为乳酸菌显性组（LD）和非乳酸菌显性组（NLD）。我们评估了NLD中细菌载量、植入、妊娠结局和治疗反应之间的关系。此外，还评估了最佳细菌负荷范围和相关宿主因素。较高的细菌负荷与LD状态和更好的NLD治疗反应有关。虽然植入和持续妊娠率与细菌负荷没有显著相关，但观察到与妊娠结局的潜在联系。体重指数（BMI）和年龄与细菌负荷变异性无关。总之，细菌负荷的定量评估可以补充微生物群组成分析，以评估抗逆转录病毒治疗的子宫内膜环境。

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引用次数: 0

Preface: 13th International Workshop Reunion Island Reproductive Immunology, immunological tolerance and immunology of preeclampsia; 9–12 December 2024 第13届留尼汪岛生殖免疫学、免疫耐受与子痫前期免疫学国际研讨会；2024年12月9日至12日

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-12-30 DOI: 10.1016/j.jri.2025.104828

Gustaaf Dekker , Pierre-Yves Robillard , Shigeru Saito

The preface to the 13th International Workshop on Reproductive Immunology, Immunological Tolerance, and Immunology of Preeclampsia (Reunion Island, 9–12 December 2024) pays tribute to the late Professor Chris Redman, a foundational figure in recognising preeclampsia as a heterogeneous syndrome, and reflects on the ongoing influence of his two-stage model. Presentations emphasised phenotypic distinctions and immunological mechanisms. Pierre-Yves Robillard, using a comprehensive Reunion Island perinatal database, delineated three subtypes of small-for-gestational-age infants, revealing that 77 % are constitutional while most pathological fetal growth restriction (with Doppler anomalies) occurs in normotensive mothers. His analyses further established primipaternity as a major risk factor in multiparous women, comparable to primigravidity and chronic hypertension, contrasting with the modest effects of birth interval. Gustaaf Dekker clarified that immune maladaptation primarily underlies early-onset preeclampsia, not the more common late-onset form driven by placental senescence. Gabor Than positioned early-onset preeclampsia within the great obstetrical syndromes linked to impaired deep placentation, advocating first-trimester screening and prevention strategies applicable across related disorders. Contributions from Oslo (Anne Cathrine Staff, Daniel Pitz Jacobsen) linked fetal microchimerism to placental dysfunction and maternal vascular features. Adelaide researchers (Sarah Robertson, Alison Care) highlighted regulatory T-cell deficits in spiral artery remodelling and pregnancy tolerance. Other talks explored immune intolerance in oocyte donation pregnancies (Michael Eikmans), personalised uterine immune profiling for IVF success (Nathalie Ledee), lymphocyte-driven autoantibodies and complement activation exacerbated by prior COVID-19 (Babette La Marca), endothelial glycocalyx disruption (Marco Scioscia), and ferroptosis inhibition as a novel therapeutic target via drug repurposing (Ofer Beharier). The workshop reinforced the necessity for precise clinical phenotyping—incorporating uterine artery Doppler, angiogenic biomarkers, fetal sex, birthweight centiles, and placental histology—alongside advanced immunological and genetic studies to advance understanding and management of this complex syndrome.

第13届生殖免疫学、免疫耐受和子痫前期免疫学国际研讨会（留尼尼岛，2024年12月9日至12日）的序言向已故的Chris Redman教授致敬，他是认识到子痫前期是一种异质综合征的基础人物，并反映了他的两阶段模型的持续影响。报告强调表型差异和免疫机制。Pierre-Yves Robillard使用留尼汪岛围产期综合数据库，描述了三种小胎龄婴儿亚型，显示77 %是正常的，而大多数病病性胎儿生长受限（多普勒异常）发生在血压正常的母亲身上。他的分析进一步证实，与生育间隔的适度影响相比，初产是多胎妇女的主要危险因素，与初产性和慢性高血压相当。Gustaaf Dekker澄清说，免疫适应不良主要是早发性先兆子痫的基础，而不是更常见的由胎盘衰老引起的晚发性子痫。Gabor Than将早发性先兆子痫定位于与深度胎盘受损相关的重大产科综合征中，倡导妊娠早期筛查和预防策略，适用于所有相关疾病。来自Oslo的贡献（Anne catherine Staff, Daniel Pitz Jacobsen）将胎儿微嵌合与胎盘功能障碍和母体血管特征联系起来。阿德莱德的研究人员（Sarah Robertson, Alison Care）强调了螺旋动脉重塑和妊娠耐受性中的调节性t细胞缺陷。其他演讲探讨了卵母细胞捐赠妊娠中的免疫不耐受（Michael Eikmans），试管婴儿成功的个性化子宫免疫谱（Nathalie Ledee），淋巴细胞驱动的自身抗体和补体活化（Babette La Marca），内皮糖基破坏（Marco Scioscia），以及通过药物重新利用抑制铁垂症作为新的治疗靶点（Ofer Beharier）。研讨会强调了精确临床表型的必要性，包括子宫动脉多普勒、血管生成生物标志物、胎儿性别、出生体重百分数和胎盘组织学，以及先进的免疫学和遗传学研究，以促进对这种复杂综合征的理解和管理。

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引用次数: 0

MCT1 supports syncytiotrophoblast function and placental development in early pregnancy MCT1支持妊娠早期合体滋养细胞功能和胎盘发育

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-12-29 DOI: 10.1016/j.jri.2025.104829

Ruizhi Chen , Jiahui Xiao , Guanying You , Linlin Wang , Gang Feng , Lianghui Diao , Yuye Li

Spontaneous miscarriage affects approximately 15 % of clinically recognized pregnancies, often due to impaired placental development. While syncytiotrophoblast (STB) is essential for nutrient exchange and hormonal support, the molecular pathways that maintains function remain incompletely defined. Here, we identify monocarboxylate transporter 1 (MCT1) as a novel metabolic regulator of placental development. We show that MCT1 expression is markedly reduced in the villi of patients with spontaneous miscarriage, correlating with abnormal lactate accumulation. Using a mouse model, we demonstrate that MCT1 inhibition leads to pregnancy failure and impaired formation of the placental labyrinth, the key site for maternal-fetal exchange. Functional and transcriptomic analyses reveal that MCT1 deficiency disrupts syncytiotrophoblast organization and downregulates transcriptional regulators critical for trophoblast function. These findings suggest that MCT1 supports early pregnancy through the trophoblast gene regulatory networks and identify it as a potential target in reproductive failure.

自发性流产影响约15% %的临床确认妊娠，通常是由于胎盘发育受损。虽然合胞滋养细胞（STB）对营养交换和激素支持至关重要，但维持其功能的分子途径仍未完全确定。在这里，我们发现单羧酸转运蛋白1 （MCT1）是胎盘发育的一种新的代谢调节因子。我们发现自发性流产患者的绒毛中MCT1的表达明显降低，这与异常的乳酸积累有关。通过小鼠模型，我们证明MCT1抑制导致妊娠失败和胎盘迷宫的形成受损，胎盘迷宫是母胎交换的关键部位。功能和转录组学分析显示，MCT1缺乏会破坏合体滋养细胞的组织，并下调对滋养细胞功能至关重要的转录调节因子。这些发现表明MCT1通过滋养细胞基因调控网络支持早期妊娠，并将其确定为生殖失败的潜在靶点。

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引用次数: 0

Human leukocyte antigens and fetal microchimerism: Relating fetal-origin cells in maternal circulation to maternal and fetal HLA genetics 人类白细胞抗原和胎儿微嵌合：母体循环中胎儿来源细胞与母体和胎儿HLA遗传学的关系。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-12-22 DOI: 10.1016/j.jri.2025.104826

Daniel P. Jacobsen , Maria B. Olsen , Heidi E. Fjeldstad , Meryam Sugulle , Anne Cathrine Staff

Fetal microchimerism denotes the presence of small amounts of fetal cells within the mother, which may persist for decades after pregnancy. The mechanisms by which these semiallogeneic cells avoid alloreactivity and manage to persist for years within the host are unknown. Previous reports have linked microchimerism to human leukocyte antigen (HLA) variants, such as HLA-C groups based on killer cell Immunoglobulin-like receptor (KIR) reactivity, HLA-DQA1*05:01, and soluble HLA-G (sHLA-G). In the present study, we attempt to verify these associations during pregnancy and postpartum. We included 255 pregnant women and 188 women between one and eight years postpartum. Data on HLA-C and HLADQA genotypes, as well as maternal circulating sHLA-G were available for a varying number of women, with cohorts ranging from 167 to 252 during pregnancy and 79–118 postpartum. Maternal and fetal HLA-C groups did not correlate with microchimerism during pregnancy or postpartum. HLA-C group mismatch from the perspective of the mother, on the other hand, negatively correlated with presence and quantity of fetal microchimerism in maternal circulation in the postpartum cohort, but not during pregnancy. Neither HLA-DQA1*05:01 nor circulating levels of sHLA-G were associated with microchimerism measurements. We confirm a negative correlation between circulating fetal microchimerism postpartum and fetal-maternal HLA-C mismatch based on KIR reactivity. Considering that such an association was not found at an HLA-C allele level in a previous publication, our present observation indicates that the interaction between microchimeric cell HLA-C variants and host killer-cell immunoglobulin-like receptors may be relevant for the longevity of microchimerism.

胎儿微嵌合是指母亲体内存在少量胎儿细胞，这种情况可能在怀孕后持续数十年。这些半同种异体细胞避免同种异体反应并设法在宿主体内存活数年的机制尚不清楚。先前的报道将微嵌合与人类白细胞抗原（HLA）变异联系起来，例如基于杀伤细胞免疫球蛋白样受体（KIR）反应性的HLA- c组，HLA- dqa1 *05:01和可溶性HLA- g （sHLA-G）。在目前的研究中，我们试图验证这些关联在怀孕和产后。我们纳入了255名孕妇和188名产后1至8年的妇女。关于HLA-C和HLADQA基因型以及产妇循环sHLA-G的数据可用于不同数量的妇女，队列从怀孕期间的167 - 252和产后的79-118不等。母体和胎儿HLA-C组与妊娠或产后的微嵌合无关。另一方面，从母亲的角度来看，HLA-C组错配与产后队列中母体循环中胎儿微嵌合的存在和数量呈负相关，但在怀孕期间则无相关。HLA-DQA1*05:01和sHLA-G的循环水平均与微嵌合测量无关。基于KIR反应性，我们证实了产后循环胎儿微嵌合与胎儿-母体HLA-C错配之间的负相关。考虑到在之前的出版物中没有发现在HLA-C等位基因水平上存在这种关联，我们目前的观察表明，微嵌合细胞HLA-C变体与宿主杀伤细胞免疫球蛋白样受体之间的相互作用可能与微嵌合的寿命有关。

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引用次数: 0

Predicting cardiovascular disease after preeclampsia: Emerging tools and early detection approaches 预测子痫前期后心血管疾病：新兴工具和早期检测方法。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-12-22 DOI: 10.1016/j.jri.2025.104827

Chiara Alfaré , Emma M. Giesen , Evelyn A. Huhn , Tullio Ghi , Stefan Verlohren , Sandra M. Blois

Preeclampsia (PE) in a previous pregnancy is a recognized risk factor for the development of long-term cardiovascular disease (CVD). However, evidence-based guidelines for cardiovascular follow-up in women with a history of PE are lacking. Given the substantial burden of CVD on individual health and society, the identification of predictive tools and strategies for its early detection in this population is crucial. The aim of this review is to summarize current evidence regarding available approaches for CVD prediction and early diagnosis following PE. Circulating biomarkers have emerged as potential tools. Elevated levels of antiangiogenic markers, such as sFlt1 (soluble vascular endothelial growth factor receptor 1) and sEng (soluble endoglin), and the sFlt1/PlGF ratio during pregnancy, have been correlated with subclinical myocardial dysfunction during the third trimester and with postpartum hypertension. Increased IL-6 several years after hypertensive disorders of pregnancy (HDP) suggests persistent systemic inflammation, while elevated activin A indicates ongoing cardiac stress. Imaging techniques also provide valuable insights. Global longitudinal strain (GLS) has emerged as a sensitive echocardiographic parameter for detecting early myocardial impairment and predicting future cardiovascular risk. Additionally, the Ultrasonic Cardiac Output Monitor (USCOM), a non-invasive hemodynamic tool, has been proposed for tailoring antihypertensive therapy in HDP and may hold potential for postpartum cardiovascular surveillance. Together, these findings support the role of circulating biomarkers, advanced echocardiography and non-invasive hemodynamic monitoring in refining cardiovascular risk stratification after PE. Further research is warranted to validate these tools and establish targeted surveillance and preventive strategies for women at long-term risk of CVD.

先前妊娠的先兆子痫（PE）是长期心血管疾病（CVD）发展的公认危险因素。然而，缺乏有PE病史的女性心血管随访的循证指南。鉴于心血管疾病对个人健康和社会造成的巨大负担，确定在这一人群中早期发现心血管疾病的预测工具和策略至关重要。本综述的目的是总结目前关于PE后CVD预测和早期诊断的可用方法的证据。循环生物标志物已成为潜在的工具。妊娠期抗血管生成标志物，如可溶性血管内皮生长因子受体1 （sFlt1）和可溶性内啡肽（sEng）水平升高，以及sFlt1/PlGF比值与妊娠晚期亚临床心肌功能障碍和产后高血压相关。妊娠期高血压疾病（HDP）数年后IL-6升高提示持续的全身性炎症，而激活素A升高提示持续的心脏应激。成像技术也提供了有价值的见解。全球纵向应变（GLS）已成为一个敏感的超声心动图参数检测早期心肌损伤和预测未来的心血管风险。此外，超声心输出量监测仪（USCOM）是一种非侵入性血流动力学工具，已被建议用于HDP患者的量身定制降压治疗，并可能具有产后心血管监测的潜力。总之，这些发现支持循环生物标志物、高级超声心动图和无创血流动力学监测在肺动脉栓塞后细化心血管风险分层中的作用。需要进一步的研究来验证这些工具，并为有心血管疾病长期风险的妇女建立有针对性的监测和预防策略。

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引用次数: 0

Tacrolimus treatment in reproductive failures 他克莫司治疗生殖失败。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-12-19 DOI: 10.1016/j.jri.2025.104824

Koji Nakagawa , Yuji Orita , Keiji Kuroda , Rikikazu Sugiyama , Koushi Yamaguchi

Immunotherapy for repeated implantation failure (RIF) following in vitro fertilization (IVF), particularly treatment with the calcineurin inhibitor tacrolimus—has now been used for roughly a decade since its initial report. In that initial series, the clinical pregnancy rate was 64.0 %; however, acceptance was slow. A recent re-evaluation at our center yields a similarly high clinical pregnancy rate of 57.1 %. In our earlier cohort, 37.7 % of RIF cases showed Th1/Th2 cell ratio suggestive of immune-mediated rejection; a more recent survey found a comparable proportion (35.9 %), indicating that approximately one-third of RIF may involve an immune component. Tacrolimus has also shown promise in immunologically mediated recurrent pregnancy loss (RPL), and its potential indications may extend to preventing obstetric complications such as abruptio placentae, hypertensive disorders of pregnancy (HDP), and HELLP syndrome. We summarize our experience, situate it within the evolving literature, and outline priorities for confirmatory trials.

体外受精（IVF）后重复植入失败（RIF）的免疫治疗，特别是钙调磷酸酶抑制剂他克莫司的治疗，自首次报道以来已经使用了大约十年。在最初的系列中，临床妊娠率为64.0 %；然而，接受的速度很慢。最近在我们中心的一次重新评估得出了同样高的临床妊娠率57.1% %。在我们早期的队列中，37.7 %的RIF病例显示Th1/Th2细胞比例提示免疫介导的排斥反应；最近的一项调查发现了类似的比例（35.9 %），表明大约三分之一的RIF可能涉及免疫成分。他克莫司在免疫介导的复发性妊娠丢失（RPL）中也显示出前景，其潜在适应症可能扩展到预防产科并发症，如胎盘早剥、妊娠高血压疾病（HDP）和HELLP综合征。我们总结了我们的经验，将其置于不断发展的文献中，并概述了验证试验的优先事项。

引用次数: 0