Journal of Reproductive Immunology最新文献

英文中文

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

PCOS phenotypes and hematological immune-inflammatory indices: A comparative evaluation 多囊卵巢综合征表型和血液学免疫炎症指标：比较评价。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-12-15 DOI: 10.1016/j.jri.2025.104823

Aykut Kından , Goncagül Kından , Çağanay Soysal , Volkan Turan

To evaluate hematological immune-inflammatory indices across different polycystic ovary syndrome (PCOS) phenotypes and assess their potential as diagnostic biomarkers. This retrospective cross-sectional study included 89 women aged 18–40 years diagnosed with PCOS according to the Rotterdam criteria, stratified into four phenotypes (A–D). Demographic, anthropometric, reproductive, biochemical, and hormonal data were extracted from clinical records. Hematological indices were calculated from complete blood counts. Group comparisons were performed using appropriate statistical tests, correlations with metabolic and hormonal parameters were assessed, and logistic regression analyses were conducted to identify independent predictors. Phenotype A demonstrated significantly higher body mass indeks (BMI), waist circumference, fasting glucose, insulin, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) values compared with other phenotypes (all p < 0.01). Neutrophil-to-Lymphocyte Ratio (NLR), Monocyte-to-Lymphocyte Ratio (MLR), and Systemic Immune-Inflammation Index (SII) differed significantly across phenotypes, whereas Platelet-to-Lymphocyte Ratio (PLR) did not. ROC analysis revealed that SII had the highest discriminative ability (AUC=0.822, p < 0.001). NLR (AUC=0.663, p = 0.020) and MLR (AUC=0.642, p = 0.043) also showed moderate predictive value. Correlation analyses indicated positive associations of NLR and SII with total testosterone and Free Androgen Index (FAI), and negative correlations with Sex Hormone-Binding Globulin (SHBG) and High-Density Lipoprotein (HDL) cholesterol. Logistic regression identified BMI, SII, and LH/FSH ratio as independent predictors of specific phenotypes, further supporting their role as clinically relevant biomarkers. Hematological immune-inflammatory indices, particularly SII, may serve as cost-effective and accessible biomarkers for distinguishing PCOS phenotypes.

评估不同多囊卵巢综合征（PCOS）表型的血液学免疫炎症指数，并评估其作为诊断生物标志物的潜力。这项回顾性横断面研究包括89名年龄在18-40岁的女性，根据鹿特丹标准诊断为PCOS，分为四种表型（A-D）。从临床记录中提取人口统计学、人体测量学、生殖学、生化学和激素数据。血液学指标由全血细胞计数计算。采用适当的统计检验进行组间比较，评估与代谢和激素参数的相关性，并进行逻辑回归分析以确定独立预测因子。与其他表型相比，表型A表现出更高的体重指数（BMI）、腰围、空腹血糖、胰岛素和胰岛素抵抗稳态模型评估（HOMA-IR）值

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引用次数: 0

Effect of changing sperm donor in the second treatment cycle on the rates of pregnancy, live birth and miscarriage 在第二个治疗周期改变精子供体对妊娠率、活产率和流产率的影响。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-12-07 DOI: 10.1016/j.jri.2025.104821

Emelie Ekwurtzel , Sofia de Sousa Soares , Camilla Stenfelt , Cina Nyberg , Aisling Ahlström , Marie-Therese Vinnars

Women with longer exposure to paternal antigens, such as a long duration of sexual cohabitation, are known to have a higher chance of successful placentation. However, it is still unknown how repeated exposure to the same sperm donor affects the outcome. We have studied the rates of pregnancy, live birth, and miscarriage among 1077 women undergoing IUI or IVF/ICSI, using either the same donor during two consecutive treatment cycles or two separate donors. Oocyte donation and frozen embryo transfer cycles were excluded. No difference was found either in pregnancy rate or live birth rate when comparing repeated treatments with the same donor (n = 815) to treatments with two separate donors (n = 262) (success rate (SR) 0.96, 95 % CI 0.75–1.23, p = 0.75; SR 1.18, 95 % CI 0.84–1.65, p = 0.33, respectively). A significant difference in miscarriage rate was observed (relative risk (RR) 0.58, 95 % CI 0.35–0.96, p = 0.03). However, after adjusting for treatment method, maternal age, BMI, and individual clinic, no significant differences were observed in any of the outcomes: pregnancy rate (adjusted SR 1.05, 95 % CI 0.79–1.39, p = 0.76), live birth rate (adjusted SR 1.20, 95 % CI 0.83–1.73, p = 0.33), or miscarriage rate (adjusted RR 0.61, 95 % CI 0.33–1.12, p = 0.11). Consequently, this study could not demonstrate any advantageous effects of repeatedly using the same sperm donor on pregnancy rate or live birth rate. However, given the limited sample size, an effect on the miscarriage rate cannot be ruled out.

与父亲抗原接触时间较长的女性，如长期的性同居，有更高的成功分娩的机会。然而，目前尚不清楚反复接触同一精子供体对结果的影响。我们研究了1077名接受IUI或IVF/ICSI的妇女的怀孕率、活产率和流产率，这些妇女在两个连续的治疗周期中使用同一个供体或使用两个不同的供体。排除卵母细胞捐赠和冷冻胚胎移植周期。使用同一供体（n = 815）进行重复治疗与使用两个单独供体（n = 262）进行重复治疗相比，妊娠率和活产率均无差异(成功率（SR） 0.96, 95 % CI 0.75-1.23, p = 0.75；SR 1.18, 95 % CI 0.84-1.65, p = 0.33)。两组流产率差异有统计学意义（相对危险度（RR） 0.58, 95 % CI 0.35-0.96, p = 0.03）。然而,在调整了治疗方法,产妇年龄、BMI,和个体诊所,没有观察到显著差异的结果:怀孕率(SR调整1.05,95 %可信区间0.79 - -1.39,p = 0.76),活产率(SR调整1.20,95 %可信区间0.83 - -1.73,p = 0.33),或流产率(RR 0.61,调整95 %可信区间0.33 - -1.12,p = 0.11)。因此，本研究不能证明重复使用同一精子供体对怀孕率或活产率有任何有利影响。然而，由于样本量有限，不能排除对流产率的影响。

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引用次数: 0

Preeclampsia 2.0: The urgent need for new thinking 子痫前期2.0：迫切需要新思维

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-12-04 DOI: 10.1016/j.jri.2025.104820

Berthold Huppertz

Preeclampsia is a pregnancy-specific syndrome with clinical symptoms including hypertension and a multitude of organ dysfunctions of the pregnant woman. So far, the etiology of preeclampsia is unclear, and a vast number of hypotheses has been created to explain the onset and pathophysiological pathways of the syndrome. Unfortunately, all of the theories suffer from the fact that they cannot explain the whole spectrum of symptoms and timing during pregnancy. Therefore, this review tries to elucidate published data that offer the opportunity to decipher earlier stages of the syndrome. Data will be listed and merged that have been obtained prior to pregnancy or during the first trimester of pregnancy from women developing preeclampsia later in this pregnancy. This allows looking into alterations of placental cells and tissues occurring long before onset of clinical symptoms. The respective data clearly shows changes of the villous trophoblast already during and at the end of the first trimester in all types of preeclampsia. This set of data may help in generating new ideas to allow the creation of new hypotheses that may better explain the diversity of the syndrome.

子痫前期是一种妊娠特异性综合征，临床症状包括孕妇高血压和多种器官功能障碍。到目前为止，先兆子痫的病因尚不清楚，并且已经创建了大量的假设来解释该综合征的发病和病理生理途径。不幸的是，所有的理论都无法解释怀孕期间的所有症状和时间。因此，本综述试图阐明发表的数据，提供机会破译早期阶段的综合征。将列出并合并妊娠前或妊娠头三个月期间从妊娠后期发生先兆子痫的妇女获得的数据。这使得观察胎盘细胞和组织的改变发生在临床症状发作之前很久。各自的数据清楚地显示绒毛滋养层的变化已经在所有类型的子痫前期和结束的前三个月。这组数据可能有助于产生新的想法，从而允许创建新的假设，从而更好地解释该综合征的多样性。

引用次数: 0

Exploring the blood-testis-barrier dynamics by targeting Laminin-α2: ADMET, molecular docking, and dynamics simulation study 以层粘连蛋白-α2: ADMET为靶点探讨血睾丸屏障动力学、分子对接及动力学模拟研究。

IF 2.9 3区医学 Q3 IMMUNOLOGY

Journal of Reproductive Immunology

Pub Date : 2025-12-02 DOI: 10.1016/j.jri.2025.104819

Uddesh Ramesh Wanjari, Abilash Valsala Gopalakrishnan

Laminin-α2 (LAMA2) is a critical regulatory protein of the blood-testis barrier (BTB), essential for preserving its structural and functional integrity. This study aims to decipher the interaction of LAMA2, BTB-regulating protein with melatonin (MLT). As there is no FDA-approved drug for male infertility, clomiphene (CP) was considered an off-market conventional drug for male infertility treatment. Molecular docking of MLT and CP with LAMA2 was performed. Molecular dynamic simulations (MDS) of LAMA2 with MLT revealed the top docked complex and had a binding energy of −88.030 ± 12.687 kJ/mol as compared with CP which had −62.952 ± 9.677 kJ/mol. Additionally, MDS analysis revealed that MLT formed a higher number of H-bonds compared to CP, producing a more compact and stable LAMA-MLT complex. Additionally, SASA, RG, and MM-PBSA binding energies studies confirmed the result. Our in-silico study predicted MLT could be a potential drug candidate for interaction with LAMA2 expressions, thereby maintaining BTB integrity. This study is one of the first reports on the molecular interaction and potential of MLT in targeting LAMA2 that provides an overview of its regulation on significant BTB-regulating proteins.

层粘连蛋白-α2 （LAMA2）是血睾丸屏障（BTB）的关键调节蛋白，对维持其结构和功能完整性至关重要。本研究旨在揭示btb调节蛋白LAMA2与褪黑激素（MLT）的相互作用。由于目前还没有fda批准的治疗男性不育症的药物，克罗米芬（CP）被认为是一种用于治疗男性不育症的非上市常规药物。MLT和CP与LAMA2进行分子对接。MLT对LAMA2的分子动力学模拟（MDS）表明，LAMA2与CP的结合能分别为-88.030 ± 12.687 kJ/mol和-62.952 ± 9.677 kJ/mol。此外，MDS分析显示，与CP相比，MLT形成了更多的氢键，产生了更紧凑和稳定的LAMA-MLT复合物。此外，SASA、RG和MM-PBSA结合能研究也证实了这一结果。我们的计算机研究预测，MLT可能是与LAMA2表达相互作用的潜在候选药物，从而维持BTB的完整性。这项研究是首次报道MLT靶向LAMA2的分子相互作用和潜力，概述了其对重要btb调节蛋白的调控作用。

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