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Association Between SARS-COV-2 Infection and Sperm DNA Fragmentation: A Systematic Review and Meta-Analysis SARS-COV-2感染与精子DNA断裂的关系:系统综述和荟萃分析
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-08-19 DOI: 10.1111/aji.70143
Zahra Asadi, Asad Vaisi-Raygani, Roya Safari-Faramani, Mahmoud Ghasemi, Faranak Aghaz

Introduction

SARS-CoV-2 infection affects various sperm quality parameters. This study examines the impact of COVID-19 infection on sperm DNA fragmentation (SDF).

Methods

A systematic literature search was performed across four databases for studies published between January 1, 2019, and January 1, 2025. The inclusion criteria focused on studies evaluating sperm DNA fragmentation in healthy men infected with the virus. The risk of bias was assessed using the Newcastle–Ottawa scale (NOS). A meta-analysis was conducted using a random effects model based on the tests employed in the studies to measure SDF. Data were reported as weighted mean differences (WMD) and corresponding 95% confidence intervals (CI). Out of 105 identified citations, seven articles were included in this analysis. The NOS results indicated that all studies were of high quality. Subgroup analysis revealed that all testing methods, including TUNEL, flow cytometry, and the sperm chromatin dispersion (SCD) test, demonstrated high heterogeneity, with the lowest heterogeneity found in the TUNEL test.

Results

The pooled analysis indicated a statistically significant increase in SDF (random effects model, WMD = 12.558, 95% CI: 4.482 to 20.635, I2 = 99%, Z = 3.05, p < 0.0001). This meta-analysis suggests a statistically significant reduction in sperm DNA integrity 2–3 months following COVID-19 infection.

Conclusion

However, caution is warranted when interpreting these results due to the high heterogeneity, which may affect the outcomes. A thorough analysis considering participant characteristics and infection status is recommended.

SARS-CoV-2感染影响精子各项质量参数。本研究探讨了COVID-19感染对精子DNA片段化(SDF)的影响。方法系统检索2019年1月1日至2025年1月1日期间发表的4个数据库的文献。纳入标准侧重于评估感染该病毒的健康男性精子DNA断裂的研究。偏倚风险采用纽卡斯尔-渥太华量表(NOS)进行评估。采用随机效应模型对研究中采用的SDF测量方法进行meta分析。数据以加权平均差(WMD)和相应的95%置信区间(CI)报告。在105个确定的引用中,有7篇文章被纳入了本分析。NOS结果显示所有研究均为高质量。亚组分析显示,包括TUNEL、流式细胞术和精子染色质分散(SCD)检测在内的所有检测方法均表现出高度的异质性,TUNEL检测的异质性最低。结果合并分析显示,SDF增加有统计学意义(随机效应模型,WMD = 12.558, 95% CI: 4.482 ~ 20.635, I2 = 99%, Z = 3.05, p < 0.0001)。这项荟萃分析表明,在感染COVID-19后2-3个月,精子DNA完整性显著降低。然而,由于高度异质性,在解释这些结果时需要谨慎,这可能会影响结果。建议考虑参与者的特征和感染状况进行彻底的分析。
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引用次数: 0
Relationship Between Serum Autotaxin Levels and Fasting Bile Acid in Intrahepatic Cholestasis of Pregnancy 妊娠肝内胆汁淤积症患者血清自taxin水平与空腹胆汁酸的关系
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-08-18 DOI: 10.1111/aji.70142
Zuhal Köksal, Tuğba Ağbal, Funda Güçel, Şeyma Sarışen

Objective

Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disease, especially in the second and third trimesters of pregnancy. Autotaxin (ATX) has been reported to play a critical role, especially in cholestatic pruritus, and serum ATX levels are associated with ICP. The aim of this study was to determine the serum ATX level in ICP, to evaluate its relationship with fasting bile acid (FBA) level, and its use in the diagnosis of ICP.

Methods

Forty-three patients diagnosed with ICP and 45 healthy pregnant women were included in the study. Gestational week at diagnosis, serum parameters, FBA, pruritus intensity, gestational week, and birth weight were recorded. Venous blood was collected from all patients for ATX levels, stored under appropriate conditions, and measured enzymatically after the study was completed.

Results

Although ATX level was found to be higher in patients with ICP (n = 43; 350.5 ± 348.7 pg/mL) compared to the control group (n = 45; 219.7 ± 131.5 pg/mL), this increase was not statistically significant (p = 0.325). Again, no significant correlation was found between ATX levels and FBA levels (p = 0.326). There was a weak correlation between the severity of pruritus and serum FBA levels (p = 0.024), but no correlation was found between ATX levels and pruritus severity (p = 0.437).

Conclusion

There was no significant difference in autotoxin levels in pregnant women with ICP compared to healthy pregnant women. These findings suggest that autotoxin activity may not be appropriate for the diagnosis of ICP, and larger clinical studies are needed to understand the effect of autotoxin in ICP.

目的妊娠肝内胆汁淤积症(ICP)是最常见的妊娠相关肝脏疾病,尤其是在妊娠中期和晚期。Autotaxin (ATX)已被报道起关键作用,特别是在胆汁淤积性瘙痒中,血清ATX水平与ICP相关。本研究的目的是测定ICP患者血清ATX水平,评估其与空腹胆汁酸(FBA)水平的关系,及其在ICP诊断中的应用。方法选择43例ICP患者和45例健康孕妇为研究对象。记录诊断时的妊娠周、血清参数、FBA、瘙痒强度、妊娠周和出生体重。收集所有患者静脉血检测ATX水平,保存在适当的条件下,并在研究结束后进行酶学测定。结果虽然发现ICP患者的ATX水平较高(n = 43;350.5±348.7 pg/mL),与对照组(n = 45;219.7±131.5 pg/mL),差异无统计学意义(p = 0.325)。同样,ATX水平与FBA水平无显著相关性(p = 0.326)。瘙痒严重程度与血清FBA水平呈弱相关(p = 0.024),而ATX水平与瘙痒严重程度无相关性(p = 0.437)。结论ICP孕妇自身毒素水平与健康孕妇无显著差异。这些发现提示,自体毒素活性可能不适合用于ICP的诊断,需要更大规模的临床研究来了解自体毒素在ICP中的作用。
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引用次数: 0
SMURF2 Inhibits Autophagy and Growth in Ovarian Cancer by Regulating the RACK1/AKT/mTOR Pathway SMURF2通过调控RACK1/AKT/mTOR通路抑制卵巢癌自噬和生长
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-08-18 DOI: 10.1111/aji.70140
Lei Wu, Ziyi Xiao, Siyue Zhang, Li Guo, Xiaojian Liu, Lihua Zhang, Jingjing Xu, Mengmeng Lv, Jinhua Wang

Background

Ovarian cancer (OC) is a common malignancy characterized by disseminated peritoneal metastases. Smad ubiquitin regulatory factor 2 (SMURF2) is involved in OC progression by stabilizing receptor for activated C kinase 1 (RACK1). However, the functions and mechanisms of action of SMURF2 in OC remain unclear. This biological function of SMURF2 in OC and its potential mechanisms of action were investigated in this study.

Methods

The expression of SMURF2 in ovarian tumor tissues, patient serum, and OC cell lines was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and/or western blotting. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays, flow cytometry, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) were used for detecting cell proliferation and apoptosis. Autophagosomes in SKOV3 cells were observed using transmission electron microscopy. Immunohistochemistry and RT-qPCR were performed to evaluate SMURF2 expression. The levels of proteins related to autophagy and RACK1 were measured using western blotting and RT-qPCR, respectively. Western blotting was performed to assess the expression of AKT/mTOR pathway-related proteins.

Results

SMURF2 was underexpressed in OC tissues and cell lines compared with that in adjacent normal tissues or normal ovarian epithelial cells. RT-qPCR results suggested that SMURF2 was downregulated in the serum of patients with OC. SMURF2 overexpression inhibited SKOV3 cell growth and autophagy, and induced apoptosis both in vitro and in vivo. Moreover, SMURF2 overexpression suppressed RACK1 expression in SKOV3 cells. The AKT/mTOR pathway was activated by SMURF2 overexpression in SKOV3, and OC cells and tissues.

Conclusions

SMURF2 plays a key role in OC by inhibiting cell autophagy and growth via activation of the RACK1/AKT/mTOR pathway, which might potentially be a new biomarker for OC diagnosis and therapy.

卵巢癌(OC)是一种常见的恶性肿瘤,以播散性腹膜转移为特征。Smad泛素调节因子2 (SMURF2)通过稳定活化C激酶1 (RACK1)受体参与OC的进展。然而,SMURF2在OC中的功能和作用机制尚不清楚。本研究探讨了SMURF2在OC中的生物学功能及其潜在的作用机制。方法采用逆转录-定量聚合酶链反应(RT-qPCR)和/或western blotting检测SMURF2在卵巢肿瘤组织、患者血清和卵巢癌细胞株中的表达。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基- 2h -溴化四唑(MTT)检测、流式细胞术、末端脱氧核苷酸转移酶dUTP镍端标记(TUNEL)检测细胞增殖和凋亡。透射电镜观察SKOV3细胞的自噬体。免疫组织化学和RT-qPCR检测SMURF2的表达。采用western blotting和RT-qPCR分别检测自噬和RACK1相关蛋白的水平。Western blotting检测AKT/mTOR通路相关蛋白的表达。结果SMURF2在卵巢癌组织和细胞系中的表达低于相邻正常组织和正常卵巢上皮细胞。RT-qPCR结果显示,OC患者血清中SMURF2表达下调。SMURF2过表达抑制SKOV3细胞生长和自噬,诱导细胞凋亡。此外,SMURF2过表达抑制了RACK1在SKOV3细胞中的表达。SMURF2在SKOV3和OC细胞和组织中过表达激活AKT/mTOR通路。结论SMURF2通过激活RACK1/AKT/mTOR通路抑制细胞自噬和生长,在OC中发挥关键作用,可能成为OC诊断和治疗的新生物标志物。
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引用次数: 0
ATP/P2X4 Regulates Inflammation and Oxidative Stress in Endometriosis Through NLRP3 Inflammasome–Dependent Mechanisms ATP/P2X4通过NLRP3炎性体依赖机制调节子宫内膜异位症的炎症和氧化应激
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-08-15 DOI: 10.1111/aji.70132
Tingting Wu, Yan Guo

Purpose

Endometriosis (EMS) is a chronic inflammatory disorder with ectopic endometrial tissues arising in extrauterine areas. We investigated the mechanism of adenosine triphosphate (ATP)/P2X4 regulating inflammation and oxidative stress in EMS.

Methods

Normal endometrial tissues and ectopic endometrial tissues were collected, and determined for P2X4 expression by immunohistochemical staining. Normal (nESCs) and ectopic endometrial stromal cells (eESCs) were isolated and manipulated with Apyrase (a soluble ATP-diphosphohydrolase), 5-BDBD (a P2X4 receptor antagonist), or Nigericin (a NOD-like receptor 3 [NLRP3] inflammasome activator). The ATP concentration in endometrial tissues and cells were assessed through the ATP colorimetric/fluorescence assay, and cellular P2X4 expression was determined by RT-qPCR. Fluo 3-AM calcium ion fluorescence probe was utilized for detecting calcium ion concentration. Levels of inflammation-associated proteins (interleukin [IL]-1β, tumor necrosis factor-alpha [TNF-α], IL-6, IL-18), oxidative stress indicators (malondialdehyde [MDA], superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GSH-Px]), reactive oxygen species (ROS), and the NLRP3 inflammasome pathway-related proteins were determined by ELISA, DCFH-DA fluorescent probe, and Western blot.

Results

ATP and P2X4 were upregulated in EMS. Apyrase or 5-BDBD treatment or P2X4 knockdown reduced the concentration of Ca2+ and levels of IL-1β, TNF-α, IL-6, MDA, and ROS, but increased the activities of SOD, GSH-Px, and CAT in eESCs. Besides, 5-BDBD treatment decreased the expression levels of the NLRP3 inflammasome pathway-related proteins in eESCs and suppressed the secretion of IL-1β and IL-18. Nigericin could reverse the inhibitory impact of 5-BDBD on NLRP3 inflammasome activation.

Conclusion

Altogether, ATP/P2X4 aggravates inflammation and oxidative stress in EMS by activating NLRP3.

目的子宫内膜异位症(EMS)是一种发生在子宫外的慢性炎症性疾病,伴有子宫内膜组织异位。我们研究了三磷酸腺苷(ATP)/P2X4调节EMS炎症和氧化应激的机制。方法采集正常子宫内膜组织和异位子宫内膜组织,采用免疫组化染色法检测P2X4的表达。分离正常(nESCs)和异位子宫内膜基质细胞(eESCs)并用Apyrase(一种可溶性atp二磷酸水解酶)、5-BDBD(一种P2X4受体拮抗剂)或Nigericin(一种nod样受体3 [NLRP3]炎性体激活剂)处理。采用ATP比色/荧光法检测子宫内膜组织和细胞中ATP的浓度,RT-qPCR检测细胞中P2X4的表达。采用Fluo 3-AM钙离子荧光探针检测钙离子浓度。采用ELISA、DCFH-DA荧光探针、Western blot检测炎症相关蛋白(白介素[IL]-1β、肿瘤坏死因子-α [TNF-α]、IL-6、IL-18)、氧化应激指标(丙二醛[MDA]、超氧化物歧化酶[SOD]、过氧化氢酶[CAT]、谷胱甘肽过氧化物酶[GSH-Px])、活性氧(ROS)、炎性小体途径相关蛋白NLRP3水平。结果ATP和P2X4在EMS中表达上调。Apyrase或5-BDBD处理或P2X4敲除降低了eESCs中Ca2+浓度和IL-1β、TNF-α、IL-6、MDA和ROS的水平,但增加了SOD、GSH-Px和CAT的活性。此外,5-BDBD治疗降低了eESCs中NLRP3炎症小体通路相关蛋白的表达水平,抑制了IL-1β和IL-18的分泌。尼日利亚菌素可以逆转5-BDBD对NLRP3炎性体激活的抑制作用。结论ATP/P2X4通过激活NLRP3,加重了EMS的炎症和氧化应激。
{"title":"ATP/P2X4 Regulates Inflammation and Oxidative Stress in Endometriosis Through NLRP3 Inflammasome–Dependent Mechanisms","authors":"Tingting Wu,&nbsp;Yan Guo","doi":"10.1111/aji.70132","DOIUrl":"https://doi.org/10.1111/aji.70132","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Endometriosis (EMS) is a chronic inflammatory disorder with ectopic endometrial tissues arising in extrauterine areas. We investigated the mechanism of adenosine triphosphate (ATP)/P2X4 regulating inflammation and oxidative stress in EMS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Normal endometrial tissues and ectopic endometrial tissues were collected, and determined for P2X4 expression by immunohistochemical staining. Normal (nESCs) and ectopic endometrial stromal cells (eESCs) were isolated and manipulated with Apyrase (a soluble ATP-diphosphohydrolase), 5-BDBD (a P2X4 receptor antagonist), or Nigericin (a NOD-like receptor 3 [NLRP3] inflammasome activator). The ATP concentration in endometrial tissues and cells were assessed through the ATP colorimetric/fluorescence assay, and cellular P2X4 expression was determined by RT-qPCR. Fluo 3-AM calcium ion fluorescence probe was utilized for detecting calcium ion concentration. Levels of inflammation-associated proteins (interleukin [IL]-1β, tumor necrosis factor-alpha [TNF-α], IL-6, IL-18), oxidative stress indicators (malondialdehyde [MDA], superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GSH-Px]), reactive oxygen species (ROS), and the NLRP3 inflammasome pathway-related proteins were determined by ELISA, DCFH-DA fluorescent probe, and Western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ATP and P2X4 were upregulated in EMS. Apyrase or 5-BDBD treatment or P2X4 knockdown reduced the concentration of Ca<sup>2+</sup> and levels of IL-1β, TNF-α, IL-6, MDA, and ROS, but increased the activities of SOD, GSH-Px, and CAT in eESCs. Besides, 5-BDBD treatment decreased the expression levels of the NLRP3 inflammasome pathway-related proteins in eESCs and suppressed the secretion of IL-1β and IL-18. Nigericin could reverse the inhibitory impact of 5-BDBD on NLRP3 inflammasome activation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Altogether, ATP/P2X4 aggravates inflammation and oxidative stress in EMS by activating NLRP3.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843448","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
Down-Regulation of Klotho/FGF23 by Low-Expressed VEGFR2 Inhibits the GH/IGF-1/PI3K/AKT Signaling Pathway Inducing Intrauterine Growth Restriction in Rats 低表达VEGFR2下调Klotho/FGF23抑制GH/IGF-1/PI3K/AKT信号通路诱导大鼠宫内生长受限
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-08-12 DOI: 10.1111/aji.70110
Li Zhang, Linlu Zheng, Yaying Cheng

Problem

Intrauterine growth restriction (IUGR) is a pregnancy complication characterized by failure of the fetus to reach its genetic growth potential. We established the association Klotho, fibroblast growth factor 23 (FGF23), and vascular endothelial growth factor receptor 2 (VEGFR2) with IUGR for the first time, hoping to provide new insights for its diagnosis and treatment.

Method of Study

Sixteen pregnant rats were randomly divided into a low-protein diet group (IUGR group) and a control group. Placental tissues were sampled to detect Klotho, FGF23, VEGFR2 mRNA, and protein expression in placental tissues of pregnant rats using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Bioinformatics methods were also used to predict the signaling pathways involved in Klotho, FGF23, and VEGFR2.

Results

The weight and crown-rump length of fetal rats in the IUGR group were significantly lower than those in the control group (p < 0.05). The expression levels of Klotho, FGF23, and VEGFR2 in IUGR group placental tissues were significantly lower than those in the control group (p < 0.05). Meanwhile, based on bioinformatics, it was predicted that VEGFR2 might affect the activation of the PI3K/AKT signaling pathway by growth hormone (GH)/insulin-like growth factor-1(IGF-1) through Klotho/FGF23 axis inhibition.

Conclusions

IUGR caused by a low protein diet reduced birth weight and crown-rump length and low expression of Klotho, FGF23, and VEGFR2 in placental tissues, which may inhibit fetal growth through the VEGFR2-Klotho-FGF23-GH-IGF-1-PI3K-AKT signaling axis.

问题宫内生长受限(IUGR)是一种以胎儿未能达到其遗传生长潜能为特征的妊娠并发症。我们首次建立了Klotho、成纤维细胞生长因子23 (FGF23)和血管内皮生长因子受体2 (VEGFR2)与IUGR的关联,希望为其诊断和治疗提供新的见解。研究方法将16只妊娠大鼠随机分为低蛋白饮食组(IUGR组)和对照组。取妊娠大鼠胎盘组织标本,采用定量实时聚合酶链反应(qRT-PCR)和western blot检测妊娠大鼠胎盘组织中Klotho、FGF23、VEGFR2 mRNA和蛋白的表达。生物信息学方法也用于预测Klotho、FGF23和VEGFR2参与的信号通路。结果IUGR组胎鼠体重和冠臀长均显著低于对照组(p <;0.05)。IUGR组胎盘组织中Klotho、FGF23、VEGFR2的表达水平显著低于对照组(p <;0.05)。同时,基于生物信息学预测,VEGFR2可能通过Klotho/FGF23轴抑制,影响生长激素(GH)/胰岛素样生长因子-1(IGF-1)激活PI3K/AKT信号通路。结论低蛋白饮食引起的IUGR降低了出生体重和冠臀长,降低了胎盘组织中Klotho、FGF23和VEGFR2的表达,可能通过VEGFR2-Klotho-FGF23- gh - igf -1- pi3k - akt信号轴抑制胎儿生长。
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引用次数: 0
Identification of Immunophenotypes as a Mediator of Gut Microbiota-Driven Female Anovulation-Induced Infertility: A Mediation Mendelian Randomization Study 鉴定免疫表型作为肠道微生物群驱动的女性无排卵诱导不孕的中介:一项中介孟德尔随机研究
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-08-11 DOI: 10.1111/aji.70135
Xiyin Wang, Jing Zhang, Xianyuan Yi, Duozhen Chen

Background

The mediatory roles of immune cells in the gut microbiota and anovulation-induced infertility remain unclear. This study aimed to investigate the correlations among gut microbiota, immunophenotypes, and anovulation-induced female infertility using a mediation Mendelian randomization (MR) study.

Methods

An MR design investigates the causal links among gut microbiota (n = 14 306, 195 bacterial taxa), 731 immunophenotypes, and anovulation-induced female infertility (5667 anovulation-induced infertile women and 117 098 controls). The causal effects were evaluated by MR Egger, weighted median, inverse variance weighted (IVW), simple mode method, and weighted mode.

Results

Two phylum members (Cyanobacteria and Bacteroidetes), an order member (Burkholderiales), a family member (Defluviitaleaceae), and seven genus members were causally correlated with the anovulation-induced infertility. Among the seven genera, Subdoligranulum, Clostridium innocuum group, and Escherichia.Shigella were the risk factors, and Prevotella9, Ruminococcus torques group, Eubacterium ventriosum group, and Eubacterium fissicatena group were the protective factors in anovulation-induced infertility. Next, 35 immunophenotypes were identified to be also causally correlated with the anovulation-induced infertility. Among them, 15 immunophenotypes were significantly driven by the seven-microbiota genus and might be the internal mediating mechanism of the influence of gut microbiota on anovulation-induced female infertility. In the mediated MR analysis, four (Clostridium innocuum group, Eubacterium fissicatena group, Eubacterium ventriosum group, and Prevotella9) of the microbiota were directly influenced by six immunophenotypes (T cell, B cell, and dendritic cell panels) and then affected the anovulation-induced infertility.

Conclusion

The mediation MR study provides evidence supporting immunophenotypes as mediators of gut microbiota-influenced female infertility, especially anovulation-induced infertility.

背景免疫细胞在肠道菌群和无排卵性不孕中的调节作用尚不清楚。本研究旨在通过孟德尔随机化(MR)研究,探讨肠道微生物群、免疫表型和无排卵诱导的女性不孕症之间的相关性。方法采用磁共振设计研究肠道微生物群(n = 14 306, 195个细菌分类群)、731种免疫表型与无排卵性不孕女性(5667例无排卵性不孕女性和117 098例对照组)之间的因果关系。因果效应评价采用MR Egger、加权中位数、方差加权逆(IVW)、简单模式法和加权模式。结果2门(蓝藻门和拟杆菌门)、1目(布氏菌门)、1科(赤潮菌科)、7属与无排卵性不孕存在因果关系。在这7个属中,有低穗芽孢杆菌属、无芽梭菌属和埃希氏菌属。志贺氏菌是无排卵性不孕的危险因素,普雷沃菌、鲁米诺球菌组、室状真杆菌组和裂裂真杆菌组是无排卵性不孕的保护因素。接下来,确定了35种免疫表型也与无排卵性不孕有因果关系。其中15种免疫表型受7个菌群属的显著驱动,可能是肠道菌群影响无排卵性女性不育的内在中介机制。在介导的MR分析中,4种微生物群(无芽梭菌组、裂丝真杆菌组、室状真杆菌组和普雷沃菌9)直接受到6种免疫表型(T细胞、B细胞和树突状细胞组)的影响,进而影响无排卵性不孕。结论介导的MR研究提供了证据,支持免疫表型作为肠道微生物群影响的女性不育的介质,特别是无排卵性不孕。
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引用次数: 0
Revisiting the Link Between Factor XII and Recurrent Pregnancy Loss: A Scoping Review 重新审视因素XII与复发性妊娠丢失之间的联系:一项范围综述
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-08-04 DOI: 10.1111/aji.70127
Emma Bundgaard, Malene Kræpping Pedersen, Pinar Bor, Mustafa Vakur Bor

Pregnancy loss affects approximately 23% of women, with 1%–3% experiencing recurrent pregnancy loss (RPL), defined as two or more consecutive miscarriages. Despite extensive research, up to 50% of RPL cases remain unexplained, making it a complex issue in reproductive medicine. Coagulation Factor XII (FXII) a key component of the contact activation pathway, has been suggested to play a role in RPL. Low FXII levels may lead to placental dysfunction and hypercoagulability, increasing the risk of adverse pregnancy outcomes, including RPL. This scoping review aimed to evaluate the association between FXII levels and RPL. Literature was retrieved from the PubMed database and EMBASE by a systematic search. A total of 218 studies were identified, of which 12 met the inclusion criteria published between 1992 and 2015, encompassing a total of 2362 RPL patients. They investigated FXII activity (n = 7), the C46T polymorphism (n = 3), or autoantibodies to FXII (n = 2) association to RPL. Available evidence suggests a potential association between low FXII levels, FXII antibodies, and RPL, probably via a prothrombotic mechanism as indicated by studies conducted 10–30 years ago. This highlights the need for further and more recent research to better elucidate the role of FXII in reproductive health and pregnancy outcomes.

约23%的妇女妊娠丢失,其中1%-3%经历复发性妊娠丢失(RPL),定义为两次或两次以上连续流产。尽管进行了广泛的研究,但高达50%的RPL病例仍然无法解释,使其成为生殖医学中的一个复杂问题。凝血因子XII (FXII)是接触激活途径的关键组成部分,已被认为在RPL中发挥作用。低FXII水平可能导致胎盘功能障碍和高凝,增加不良妊娠结局的风险,包括RPL。本综述旨在评估FXII水平与RPL之间的关系。通过系统检索从PubMed数据库和EMBASE中检索文献。共纳入218项研究,其中12项符合1992年至2015年发表的纳入标准,共纳入2362例RPL患者。他们研究了FXII活性(n = 7)、C46T多态性(n = 3)或FXII自身抗体(n = 2)与RPL的关联。现有证据表明,低FXII水平、FXII抗体和RPL之间存在潜在关联,可能通过10-30年前的研究表明的血栓形成前机制。这突出表明需要进一步和更近期的研究,以更好地阐明FXII在生殖健康和妊娠结局中的作用。
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引用次数: 0
Emerging Mechanisms of NK Cell Dysfunction in Endometriosis: The Role of Autophagy, Metabolism, Cytokines, Exosomes, and Trogocytosis 子宫内膜异位症中NK细胞功能障碍的新机制:自噬、代谢、细胞因子、外泌体和巨噬细胞的作用
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-08-04 DOI: 10.1111/aji.70138
Mohammad Abbaszadeh, Mojdeh Soltani, Sara Falahi, Nafiseh Esmaeil

Endometriosis (EMS) is a persistent, inflammatory condition that relies on estrogen and is distinguished by the proliferation of endometrial tissue outside the confines of the uterus. The impact on the well-being of individuals affected can be significant, as it is linked to pelvic pain and reduced fertility in women of reproductive age. Over 30 years have passed since initially discovering a malfunction in the activity of natural killer (NK) cells in individuals with EMS. Several aspects that contribute to NK cell dysfunction have been explored by researchers over the years, such as the upregulation of inhibitory receptors, downregulation of activating receptors, and the exhaustion process. Nonetheless, there are still many aspects that have yet to be identified. The objective of this review is to explore whether there is a connection between mechanisms that have not yet been explored and the malfunctioning of EMS-derived NK cells. Autophagy, metabolism, trogocytosis, tunneling nanotubes (TNT), and exosomes are among the factors that play a role in these processes. The primary objective of this publication is to provide valuable insights for future research on NK cells, with the aim of enhancing our understanding of the disease's causes and identifying more effective targets for immunotherapy.

子宫内膜异位症(EMS)是一种依赖于雌激素的持续性炎症,以子宫外子宫内膜组织增生为特征。对受影响个体的影响可能是显著的,因为它与盆腔疼痛和育龄妇女生育能力下降有关。自最初发现EMS患者的自然杀伤(NK)细胞活性异常以来,已经过去了30多年。多年来,研究人员对NK细胞功能障碍的几个方面进行了探索,如抑制性受体的上调、激活性受体的下调和衰竭过程。尽管如此,仍有许多方面尚未确定。本综述的目的是探讨尚未探索的机制与ems衍生的NK细胞功能障碍之间是否存在联系。自噬、代谢、细胞吞噬、隧道纳米管(TNT)和外泌体是在这些过程中发挥作用的因素之一。本出版物的主要目的是为未来NK细胞的研究提供有价值的见解,目的是提高我们对疾病原因的理解,并确定更有效的免疫治疗靶点。
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引用次数: 0
Cognitive Dysfunction in Systemic Lupus Erythematosus During Pregnancy. 妊娠期系统性红斑狼疮的认知功能障碍。
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-08-01 DOI: 10.1111/aji.70134
Philippe Leff, Daniela Chinchilla-Ochoa, Efraín Olivas-Peña, Martha Lucía Granados-Cepeda, Karla Cristina Trejo-Sánchez, Blanca Eugenia Farfán-Labonne

Problem: Systemic lupus erythematosus (SLE) is characterized by an abnormal immune response, leading to elevated levels of autoantibodies that may distress the hepatic, renal, and central nervous systems. Cognitive dysfunction (CD) is the second most common neuropsychiatric symptom reported in SLE patients, after headache. CD has been linked to increased liver serum markers and kidney dysfunction in SLE patients. However, CD has not been previously described in pregnant women with SLE, although it can significantly impact decision-making and quality of life during pregnancy. Our primary goal was to assess the prevalence of CD in pregnant women with quiescent SLE (QSLE). Additionally, we aimed to describe the correlation between CD and serum levels of autoantibodies, complement system components, and hepatic and renal serology.

Method of study: We conducted a cross-section study involving QSLE pregnant women (n = 63) and healthy pregnant controls (n = 52) in their third trimester. CD was assessed using the MoCA test. Biochemical determinations were performed by ELISA, and clinical data for creatinine and urea were also analyzed.

Results: Higher CD rates were observed in QSLE pregnant women (30.16 %, QSLE CD(+)) compared to the healthy group (5.7%, CTR CD(+)). Serum levels of liver (ALT: QSLE CD(+) 65.9 ± 26.5 vs. QSLE CD(-) 39.9 ± 14.6, p = 0.00) and renal markers (urea: QSLE CD(+) 6.27 ± 2.1 vs. QSLE CD(-) 3.3 ± 1.1, p = 0.00) were significantly elevated in QSLE CD(+) pregnant women. AST and ALT showed a significant correlation with the MoCA score for QSLE CD(+) patients.

Conclusions: MoCA total score, as well as attention, visuospatial/executive, and abstraction domains were found to be impaired in QSLE CD(+) pregnant patients. Subclinical liver and kidney dysfunction were associated with cognitive impairment in QSLE pregnant women.

问题:系统性红斑狼疮(SLE)的特点是免疫反应异常,导致自身抗体水平升高,可能会损害肝脏、肾脏和中枢神经系统。认知功能障碍(CD)是SLE患者中第二大常见的神经精神症状,仅次于头痛。在SLE患者中,乳糜泻与肝脏血清标志物升高和肾功能障碍有关。然而,虽然乳糜泻会显著影响妊娠期间的决策和生活质量,但在SLE孕妇中尚未发现乳糜泻。我们的主要目的是评估静止性SLE (QSLE)孕妇乳糜泻的患病率。此外,我们旨在描述CD与血清自身抗体水平、补体系统成分和肝肾血清学之间的相关性。研究方法:我们对QSLE孕妇(n = 63)和妊娠晚期健康孕妇(n = 52)进行了横断面研究。采用MoCA试验评估CD。采用酶联免疫吸附试验(ELISA)进行生化检测,并分析肌酐和尿素的临床数据。结果:QSLE孕妇的CD发生率(30.16%,QSLE CD(+))高于健康组(5.7%,CTR CD(+))。QSLE CD(+)孕妇血清肝脏水平(ALT: QSLE CD(+) 65.9±26.5 vs QSLE CD(-) 39.9±14.6,p = 0.00)和肾脏标志物(尿素:QSLE CD(+) 6.27±2.1 vs QSLE CD(-) 3.3±1.1,p = 0.00)显著升高。QSLE CD(+)患者AST和ALT与MoCA评分有显著相关性。结论:QSLE CD(+)妊娠患者MoCA总分、注意力、视觉空间/执行和抽象域均受损。QSLE孕妇的亚临床肝肾功能障碍与认知障碍相关。
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引用次数: 0
Mendelian Randomization Study of Sex Hormone Binding Globulin and Its Influence on Adverse Pregnancy Outcomes. 性激素结合球蛋白的孟德尔随机研究及其对不良妊娠结局的影响。
IF 2.4 3区 医学 Q3 IMMUNOLOGY Pub Date : 2025-08-01 DOI: 10.1111/aji.70139
Han Wu, Yiying Jin, Qiuhui Pan, Feng Cheng, Chaoyan Yue

Background: The relationship between sex hormone-binding globulin (SHBG) levels and the risk of adverse pregnancy outcomes (APOs) remains controversial. A two-sample Mendelian randomization (MR) study was performed to clarify the causality of SHBG on the risk of APO.

Methods: Significant single-nucleotide polymorphisms (SNPs) associated with SHBG levels were obtained from the genome-wide association study (GWAS) in the European population. Summary statistics of the number of spontaneous miscarriages, preeclampsia, gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP), and female infertility were utilized as the outcome. The causality was examined primarily by inverse-variance weighted (IVW), along with MR-Egger regression, weighted median estimator, and weighted mode method.

Results: Based on the IVW model, every genetically predicted standard deviation (SD) increase in SHBG levels was causally associated with 0.023 SDs decrease of the number of spontaneous miscarriages (Beta ± SE: -0.023 ± 0.010, p = 0.018), 11.3% decrease of the risk of preeclampsia (OR = 0.887, 95% CI: 0.806-0.977, p = 0.015), 17% decrease of the risk of GDM (OR = 0.830, 95% CI: 0.753-0.914, p = 0.000), 23.6% decrease of the risk of ICP (OR = 0.764, 95% CI: 0.584-0.999, p = 0.049), and 14% decrease of the risk of infertility (OR = 0.860, 95% CI: 0.777-0.951, p = 0.003).

Conclusion: Our study indicated that the increased levels of SHBG could significantly reduce the risk of APO. SHBG may be helpful as the indicator for preconception risk assessment and pregnancy risk monitoring. These findings are limited to European and require further validation in diverse populations.

背景:性激素结合球蛋白(SHBG)水平与不良妊娠结局(APOs)风险之间的关系仍存在争议。一项双样本孟德尔随机化(MR)研究旨在阐明SHBG与APO风险之间的因果关系。方法:从欧洲人群的全基因组关联研究(GWAS)中获得与SHBG水平相关的显著单核苷酸多态性(snp)。汇总统计自然流产、子痫前期、妊娠期糖尿病(GDM)、妊娠肝内胆汁淤积(ICP)、女性不孕症的数量。因果关系主要通过反方差加权(IVW)、MR-Egger回归、加权中位数估计和加权模式方法进行检验。结果:基于IVW模型,每一个基因预测标准偏差(SD)增加SHBG水平0.023 SDs有关数量的减少自发流产(β±SE: -0.023±0.010,p = 0.018),减少11.3%的风险子痫前期(OR = 0.887, 95% CI: 0.806—-0.977,p = 0.015),减少17%的GDM的风险(OR = 0.830, 95% CI: 0.753—-0.914,p = 0.000),减少23.6%的风险ICP (OR = 0.764, 95% CI:0.584-0.999, p = 0.049),不孕风险降低14% (OR = 0.860, 95% CI: 0.777-0.951, p = 0.003)。结论:我们的研究表明,SHBG水平的升高可以显著降低APO的风险。SHBG可作为孕前风险评估和妊娠风险监测的指标。这些发现仅限于欧洲,需要在不同人群中进一步验证。
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引用次数: 0
期刊
American Journal of Reproductive Immunology
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