American Journal of Reproductive Immunology最新文献_第2页

Thyroid Autoimmunity: The Treatment of Hashimoto's Disease, or the Presence of Antithyroid Antibodies Alone, in Pregnancy 甲状腺自身免疫：治疗桥本病，或单独存在抗甲状腺抗体，在怀孕。

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2025-01-10 DOI: 10.1111/aji.70042

Jonathan Scher, Carmen Dabao, Caitlin Rukat

Problem

Hashimoto's disease is the commonest autoimmune disease of pregnancy. The presence of Anti-Thyroid antibodies (ATAs) alone [subclinical hypothyroidism] has also been shown to have adverse pregnancy effects. These can result in failure to conceive, recurrent miscarriages, anemia, preeclampsia, and abruption. Hashimoto's disease in reproduction can cause difficulty in conception through hormonal interference. It can also cause miscarriages, growth retardation, and preterm birth. The current recommended treatment is the administration of levothyroxine. This corrects the thyroid balance and may relieve the patient's hypothyroid symptoms. However, repeated recent studies have shown that it is no more effective than a placebo in correcting obstetric complications.

Method of Study

As a result, we decided to use an anti-autoimmune-directed treatment for this disorder. We selected to use IVIG for both its known powerful anti-inflammatory and anti-autoimmune benefits. There are several studies and observational reports in the literature on the use of IVIG in pregnancy for treating recurrent miscarriages and repeated failed IVF. However, there are no reports in the literature on using IVIG to treat Hashimoto's disease, or the presence of ATAs alone, in pregnancy.

Results

This study showed an increase in live births in the IVIG-treated group versus the non-IVIG-treated group after adjustment for maternal age at delivery (OR = 4.6, 95% CI (1.1, 18.1)). There were no adverse effects in the patients who received IVIG.

Conclusion

IVIG is effective in significantly improving the obstetric outcome in patients with Hashimoto's disease, or the presence of ATAs alone.

问题：桥本氏病是妊娠期最常见的自身免疫性疾病。抗甲状腺抗体（ATAs）单独存在[亚临床甲状腺功能减退]也被证明对妊娠有不良影响。这些可能导致怀孕失败，反复流产，贫血，先兆子痫和早剥。生殖中的桥本氏病可以通过激素干扰导致受孕困难。它还会导致流产、发育迟缓和早产。目前推荐的治疗方法是使用左甲状腺素。这样可以纠正甲状腺平衡，减轻患者的甲状腺功能减退症状。然而，最近反复的研究表明，在纠正产科并发症方面，它并不比安慰剂更有效。研究方法：因此，我们决定使用抗自身免疫定向治疗这种疾病。我们选择使用IVIG，因为它具有已知的强大的抗炎和抗自身免疫益处。文献中有几项研究和观察报告关于妊娠期使用IVIG治疗复发性流产和多次IVF失败。然而，文献中没有关于使用IVIG治疗妊娠期桥本氏病或单独存在ATAs的报道。结果：本研究显示，在调整产妇分娩年龄后，ivig治疗组的活产率高于非ivig治疗组（OR = 4.6, 95% CI(1.1, 18.1)）。接受IVIG治疗的患者无不良反应。结论：IVIG可显著改善桥本氏病患者的产科结局，或单独存在ATAs。

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引用次数: 0

Efficacy of Corticosteroids in Patients With Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis 皮质类固醇治疗复发性流产患者的疗效：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 : 2025-01-08 DOI: 10.1111/aji.70037

Silvia D'Ippolito, Filippo Gavi, Chiara Granieri, Chiara De Waure, Sara Giuliano, Francesco Cosentino, Chiara Tersigni, Giovanni Scambia, Nicoletta Di Simone

Recurrent pregnancy loss (RPL) represents a complication of pregnancy occurring in 1%–3% of all couples trying to conceive. About 50%–60% of RPL cases remain idiopathic, therefore therapeutic strategies seem empirical and based on unproven evidence. We investigated the efficacy of corticosteroids in women with RPL. We conducted a systematic review and meta-analysis, up to August 2024, in the PubMed, Scopus, and Web of Science databases, including studies on idiopathic RPL women and comparing corticosteroids versus control treatment. Primary outcome was the ongoing pregnancy rate beyond 12 weeks of gestation; secondary outcomes were live birth rate (LBR), stillbirth, birth weight, incidence of preeclampsia and/or gestational diabetes, gestational age at delivery, and fetal abnormalities. Four studies comprising 417 RPL women randomly assigned to steroid or control treatment were included. We found that oral corticosteroids significantly increase the ongoing pregnancy rate beyond 12 weeks of gestation compared to the control group (log OR [odds ratio] = 1.49 [0.32, 2.67], p = 0.01), with high heterogeneity (I² = 75%), and improve LBR (log OR = 0.9 [0.11, 1.69], p = 0.03), with low heterogeneity (I² = 0.05%). However, the limited number of studies significantly limits the strength of the findings. Also, the benefit/risk assessment of the use of corticosteroids in early pregnancy for RPL is still unclear.

复发性妊娠丢失（RPL）是一种妊娠并发症，发生在所有试图怀孕的夫妇中1%-3%。大约50%-60%的RPL病例仍然是特发性的，因此治疗策略似乎是经验性的，基于未经证实的证据。我们研究了皮质类固醇对女性RPL的疗效。截至2024年8月，我们在PubMed、Scopus和Web of Science数据库中进行了系统回顾和荟萃分析，包括特发性RPL女性的研究，并比较了皮质类固醇与对照治疗。主要结局是妊娠超过12周的持续妊娠率；次要结局是活产率（LBR）、死产、出生体重、先兆子痫和/或妊娠糖尿病的发生率、分娩胎龄和胎儿异常。包括417名RPL妇女的四项研究，随机分配到类固醇或对照治疗。我们发现，与对照组相比，口服皮质类固醇显著增加妊娠12周以上的持续妊娠率（对数OR[比值比]= 1.49 [0.32,2.67],p = 0.01），异质性高（I2 = 75%），改善LBR（对数OR = 0.9 [0.11, 1.69], p = 0.03），异质性低（I2 = 0.05%）。然而，有限的研究数量极大地限制了研究结果的强度。此外，在妊娠早期使用皮质类固醇治疗RPL的获益/风险评估仍不清楚。

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引用次数: 0

FOXL2 Knockdown Inhibits the Progression of Endometriosis FOXL2敲低抑制子宫内膜异位症的进展。

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2025-01-08 DOI: 10.1111/aji.70043

Bing Zhang, Shang-Jin Li, Hua Yuan, Shan-Shan Cong, Shao-Jie Zhao, Xiao-Jun Yang

Problem

Endometriosis (EM) is known as a common estrogen-dependent chronic inflammatory disease. Elevated levels of Forkhead box L2 (FOXL2) have been observed in uterine diseases, including EM. However, the molecular mechanism of FOXL2 in EM needs to be further illustrated. This study aimed to investigate the regulatory role of FOXL2 in EM rats and isolated ectopic endometrial stromal cells (EC-ESCs).

Method of Study

FOXL2 knockdown were designed to evaluate the effects of FOXL2 in EM model rats and EC-ESCs. Hematoxylin-eosin (HE) staining was used to evaluate the pathological morphology of ectopic endometrium. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) analysis and immunohistochemistry (IHC) were applied to detect the expression of FOXL2, EM-related genes, and epithelial to mesenchymal transition-related proteins. The proliferation, migration, invasion, and apoptosis of EC-ESCs were determined by 5-ethynyl-2′-deoxyuridine (EDU) assay, Transwell assay, and flow cytometry.

Results

The FOXL2 level was remarkably higher in the ectopic endometrial tissue than that in the normal endometrial tissue. Knockdown of FOXL2 notably improved the pathological morphology of EM in rats, and decreased expression levels of ER-α, ER-ß, and Cyp19a. Additionally, down-regulation of FOXL2 suppressed cells proliferation, migration and invasion, and stimulated more apoptotic cells in EC-ESCs. Besides, FOXL2-small interfering RNA (FOXL2-siRNA) treatment resulted in enhanced cleaved-Caspase3 protein expression and cleaved-Caspase3/Caspase3 ratio in EC-ESCs.

Conclusion

FOXL2 participates in the occurrence and development of EM through promoting epithelial-mesenchymal transition procession and enhancing the migration and invasion of EC-ESCs, suggesting that FOXL2 may be a new therapeutic target for the EM therapy.

问题：子宫内膜异位症（EM）是一种常见的雌激素依赖性慢性炎症性疾病。叉头盒L2 （FOXL2）水平升高已在子宫疾病中被观察到，包括EM。然而，FOXL2在EM中的分子机制需要进一步阐明。本研究旨在探讨FOXL2在EM大鼠和离体异位子宫内膜基质细胞（EC-ESCs）中的调节作用。研究方法：设计FOXL2敲低模型，评价FOXL2在EM模型大鼠和EC-ESCs中的作用。采用苏木精-伊红（HE）染色评价异位子宫内膜的病理形态。应用逆转录酶定量聚合酶链式反应（RT-qPCR）和免疫组化（IHC）检测FOXL2、em相关基因和上皮向间质过渡相关蛋白的表达。采用5-乙基-2′-脱氧尿苷（EDU）法、Transwell法和流式细胞术检测EC-ESCs的增殖、迁移、侵袭和凋亡情况。结果：异位子宫内膜组织中FOXL2水平明显高于正常子宫内膜组织。敲低FOXL2可显著改善大鼠EM的病理形态，降低ER-α、ER-ß和Cyp19a的表达水平。此外，下调FOXL2抑制了EC-ESCs细胞的增殖、迁移和侵袭，并刺激了更多的凋亡细胞。此外，foxl2小干扰RNA （FOXL2-siRNA）处理导致EC-ESCs中切割-Caspase3蛋白表达和切割-Caspase3/Caspase3比值增强。结论：FOXL2通过促进上皮-间质转化过程，增强EC-ESCs的迁移和侵袭，参与EM的发生发展，提示FOXL2可能是EM治疗的新靶点。

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引用次数: 0

SARS-CoV-2 Activated Peripheral Blood Mononuclear Cells (PBMCs) Do Not Provoke Adverse Effects in Trophoblast Spheroids SARS-CoV-2激活的外周血单核细胞（PBMCs）不会引起滋养层球体的不良反应。

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2025-01-07 DOI: 10.1111/aji.70039

Humblenoble Stembridge Ayuk, Susanne Arnold, Arkadiusz Pierzchalski, Mario Bauer, Violeta Stojanovska, Ana Claudia Zenclussen

Problem

Although it is still uncertain whether Severe Acute Respiratory Coronavirus (SARS-CoV-2) placental infection and vertical transmission occur, inflammation during early pregnancy can have devastating consequences for gestation itself and the growing fetus. If and how SARS-CoV-2-specific immune cells negatively affect placenta functionality is still unknown.

Method of study

We stimulated peripheral blood mononuclear cells (PBMCs) from women of reproductive age with SARS-CoV-2 peptides and cocultured them with trophoblast spheroids (HTR-8/SVneo and JEG-3) to dissect if SARS-CoV-2-activated immune cells can interfere with trophoblast functionality. The activation and cytokine profile of the PBMCs were determined using multicolor flow cytometry. The functionality of trophoblast spheroids was assessed using microscopy, enzyme-linked immunosorbent assay (ELISA), and RT-qPCR.

Results

SARS-CoV-2 S and M peptides significantly activated PBMCs (monocytes, NK cells, and T cells with memory subsets) and induced the upregulation of proinflammatory cytokines, such as IFNγ. The activated PBMCs did not impact the viability, growth rate, and invasion capabilities of trophoblast spheroids. Furthermore, the hormonal production of hCG by JEG-3 spheroids was not compromised upon coculture with the activated PBMCs. mRNA transcript levels of genes involved in trophoblast spheroid functional pathways were also not dysregulated after coculture.

Conclusions

Together, the findings of our in vitro coculture model, although not fully representative of in vivo conditions, strongly support the claim that the interaction of SARS-CoV-2-activated peripheral blood immune cells with trophoblast cells at the fetal–maternal interface does not negatively affect trophoblast functionality. This goes in hand with the recommendation of vaccinating pregnant women in their first trimester.

问题：虽然目前还不确定是否会发生严重急性呼吸道冠状病毒（SARS-CoV-2）胎盘感染和垂直传播，但妊娠早期的炎症会对妊娠本身和正在发育的胎儿造成毁灭性的后果。sars - cov -2特异性免疫细胞是否以及如何对胎盘功能产生负面影响尚不清楚。研究方法：我们用SARS-CoV-2肽刺激育龄妇女外周血单个核细胞（PBMCs），并将其与滋养细胞球体（HTR-8/SVneo和JEG-3）共培养，以分析SARS-CoV-2激活的免疫细胞是否会干扰滋养细胞功能。采用多色流式细胞术检测PBMCs的活化和细胞因子谱。使用显微镜、酶联免疫吸附试验（ELISA）和RT-qPCR评估滋养细胞球体的功能。结果：SARS-CoV-2 S和M肽显著激活PBMCs（单核细胞、NK细胞和具有记忆亚群的T细胞），诱导促炎细胞因子（如IFNγ）上调。活化的PBMCs不影响滋养层球体的活力、生长速度和侵袭能力。此外，JEG-3球体与活化的pbmc共培养时，hCG的激素分泌并未受到损害。滋养层球体功能通路相关基因mRNA转录水平在共培养后也未出现异常。总之，我们的体外共培养模型的发现，尽管不能完全代表体内条件，但有力地支持了这样的说法，即sars - cov -2激活的外周血免疫细胞与滋养细胞在胎儿-母体界面的相互作用不会对滋养细胞功能产生负面影响。这与建议孕妇在妊娠早期接种疫苗密切相关。

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引用次数: 0

Aging Selectively Alters PRR and ISG Expression in Endo- and Ecto-Cervical Stromal Fibroblasts From the Human Female Reproductive Tract 衰老选择性改变人类女性生殖道内、宫颈间质成纤维细胞中PRR和ISG的表达

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2025-01-07 DOI: 10.1111/aji.70031

Mickey V. Patel, Zheng Shen, Daniel C. Hopkins, Fiona D. Barr, Charles R. Wira

Problem

Aging alters immune function in women and can lead increased risk of infections, particularly in the female reproductive tract (FRT).

Method of Study

To determine how aging affects innate immune responses in the cervical stroma of the FRT, we isolated endocervical (CX) and ectocervical (ECX) stromal fibroblasts and determine if their expression of multiple pattern recognition receptors (PRRs) and responses to viral stimulation varied with menopause and age.

Results

Constitutive expression of most PRRs did not vary with age or menopausal status in either cell type. However, the expression of TLR7, MDA5, and NOD2 by ECX stromal fibroblasts significantly increased in post-menopausal women, while the expression of NOD1 by CX stromal fibroblast also significantly increased in post-menopausal women. When stratified by age, the expression of TLR6 by CX stromal fibroblasts, and MDA5 and NOD2 by ECX stromal fibroblasts increased significantly with increasing age. Stimulation with the dsRNA viral mimic HMW poly (I:C), a ligand for MDA5, resulted in significantly increased expression of the Type I interferons (IFN) IFNβ and IFNε, the Type III interferon IFNλ1, and interferon-stimulated genes (ISGs) MxA, OAS2, and ISG15 in both cell populations. However, upregulation of IFNβ, IFNλ1, MxA, OAS2, and ISG15 in response to poly (I:C) significantly declined with increasing post-menopausal age in ECX stromal fibroblasts. There was no effect of age or menopause on either IFN or ISG expression in CX stromal fibroblasts.

Conclusion

Overall, these studies demonstrate that ECX and CX fibroblasts are phenotypically distinct populations and that increasing post-menopausal age reduces IFN and ISG upregulation in ECX stromal fibroblasts in response to viral stimulation, potentially leading to decreased protection against incoming viral pathogens in older post-menopausal women.

问题：衰老会改变女性的免疫功能，并可能导致感染风险增加，尤其是在女性生殖道（FRT）。研究方法：为了确定衰老如何影响FRT宫颈间质的先天免疫反应，我们分离了宫颈内（CX）和宫颈外（ECX）间质成纤维细胞，并确定它们的多模式识别受体（PRRs）表达和对病毒刺激的反应是否随绝经和年龄而变化。结果：在两种细胞类型中，大多数PRRs的组成性表达不随年龄或绝经状态而变化。而在绝经后妇女中，ECX间质成纤维细胞表达TLR7、MDA5、NOD2显著升高，而CX间质成纤维细胞表达NOD1也显著升高。按年龄分层时，随着年龄的增加，CX间质成纤维细胞TLR6、ECX间质成纤维细胞MDA5、NOD2的表达均显著增加。dsRNA病毒模拟HMW poly (I:C) （MDA5的配体）刺激导致I型干扰素（IFN）、IFNβ和IFNε、III型干扰素IFNλ1和干扰素刺激基因（ISGs） MxA、OAS2和ISG15在两种细胞群体中的表达显著增加。然而，在ECX间质成纤维细胞中，IFNβ、IFNλ1、MxA、OAS2和ISG15对poly （I:C）的上调随着绝经后年龄的增加而显著下降。年龄或更年期对CX间质成纤维细胞中IFN或ISG的表达均无影响。结论：总的来说，这些研究表明ECX和CX成纤维细胞是表型不同的群体，绝经后年龄的增加降低了ECX间质成纤维细胞对病毒刺激的IFN和ISG上调，可能导致老年绝经后妇女对传入的病毒病原体的保护能力下降。

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引用次数: 0

Causal Relationship Between Antibody-Mediated Immune Responses of Chlamydia trachomatis Infection and Reproductive Tract Complications: A Bidirectional Mendelian Randomization Study 沙眼衣原体感染抗体介导的免疫反应与生殖道并发症的因果关系：双向孟德尔随机研究

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2025-01-07 DOI: 10.1111/aji.70036

Yanggang Hong, Yi Wang

Purpose

Characterized as a prevalent sexually transmitted infection, Chlamydia trachomatis is intimately associated with reproductive tract complications, including pelvic inflammatory disease (PID) and infertility. However, the causal relationships between C. trachomatis infection and reproductive tract complications remain elusive.

Methods

To investigate the causal relationships between C. trachomatis antibodies and seven reproductive tract complications, we conducted a bidirectional Mendelian randomization (MR) analysis. The fundamental data were originated from the genome-wide association studies (GWAS) database. While the influences of C. trachomatis antibodies on reproductive tract complications such as tubal factor infertility (TFI) and PID have been assessed, the reverse MR analysis examined how these complications impacted C. trachomatis antibodies.

Results

The forward MR analysis revealed that the upregulation of MOMP A antibodies was significantly associated with a reduced risk of TFI (OR = 0.932, p = 0.007), while MOMP D antibodies were associated with a reduced risk of ectopic pregnancy (EP) (OR = 0.923, p = 0.005). However, no significant causal interactions were identified for other reproductive complications. Moreover, the reverse MR analysis indicated that cervicitis was significantly correlated with lower MOMP A antibody levels (OR = 0.900, p = 0.016).

Conclusions

This study demonstrates the protective effects of C. trachomatis antibodies, particularly MOMP A and MOMP D, against TFI and EP, respectively. It also emphasizes the potential role of cervical inflammation in shaping immune responses to C. trachomatis. These insights provide a foundation for future research to develop immune-targeted therapies and integrated approaches for preventing and managing C. trachomatis-related reproductive tract complications.

目的：沙眼衣原体是一种常见的性传播感染，与生殖道并发症密切相关，包括盆腔炎（PID）和不孕症。然而，沙眼衣原体感染与生殖道并发症之间的因果关系尚不明确。方法：采用双向孟德尔随机化（MR）方法，探讨沙眼衣原体抗体与7种生殖道并发症的因果关系。基础数据来源于全基因组关联研究（GWAS）数据库。虽然已经评估了沙眼原体抗体对生殖道并发症（如输卵管性不孕症（TFI）和PID）的影响，但反向MR分析检查了这些并发症如何影响沙眼原体抗体。结果：正向MR分析显示，MOMP A抗体上调与TFI风险降低显著相关（OR = 0.932, p = 0.007）， MOMP D抗体上调与异位妊娠（EP）风险降低显著相关（OR = 0.923, p = 0.005）。然而，没有发现其他生殖并发症的显著因果关系。此外，反向MR分析显示宫颈炎与较低的MOMP A抗体水平显著相关（OR = 0.900, p = 0.016）。结论：本研究证实了沙眼衣原体抗体，特别是MOMP A和MOMP D分别对TFI和EP具有保护作用。它还强调了宫颈炎症在形成对沙眼衣原体的免疫反应中的潜在作用。这些见解为未来研究开发免疫靶向治疗和预防和管理沙眼衣原体相关生殖道并发症的综合方法提供了基础。

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引用次数: 0

Vaginal Transcriptional Signatures of the Neutrophil-Driven Immune Response Correlate With Clinical Severity During Recurrent Vulvovaginal Candidiasis 中性粒细胞驱动的免疫反应的阴道转录特征与复发性外阴阴道念珠菌病的临床严重程度相关。

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2025-01-07 DOI: 10.1111/aji.70040

Tyra Hasselrot, Cathrin Alvendal, Sara Hunt, Mathias Franzén Boger, Vilde Kaldhusdal, Anastasios Damdimopoulos, Ina Schuppe-Koistinen, Gabriella Edfeldt, Nina Bohm-Starke, Kristina Broliden

Problem

Recurrent vulvovaginal candidiasis (RVVC) affects 5%−10% of all women, negatively impacting their reproductive health and quality of life. Herein, we investigated the molecular effects of RVVC on the vaginal mucosa of otherwise healthy women.

Method of Study

Gene expression analysis was performed on vaginal tissue biopsies from women with RVVC, including those with a current episode of vulvovaginal candidiasis (VVC, n = 19) and women between infections (culture negative RVVC [CNR], n = 8); women asymptomatically colonized with Candida albicans (asymptomatic [AS], n = 7); and healthy controls (n = 18). Gene expression profiles were compared between groups and correlated with clinical data retrieved from questionnaires and gynecologic examinations.

Results

Of 20 171 genes identified in vaginal biopsies, 6506 were differentially expressed in the RVVC group, compared to healthy controls. Gene expression pathway analysis revealed an association between RVVC and pathways of inflammatory responses, especially genes involved in neutrophil recruitment and activation. Expression of genes involved in inflammation and neutrophil recruitment increased with increasing clinical severity of VVC, whereas expression of some genes involved in epithelial integrity decreased with increasing clinical severity of infection. Gene expression profiles of both the CNR and AS groups were comparable to those of healthy controls.

Conclusions

The clinical severity of RVVC during active infection correlates with increased expression of genes involved in molecular inflammation and neutrophil activation in the vaginal mucosa. The lack of differences between healthy controls and women with RVVC who were between acute infections indicates that the molecular effects observed in the RVVC group are only present during active infection.

问题：复发性外阴阴道念珠菌病（RVVC）影响5%-10%的妇女，对她们的生殖健康和生活质量产生负面影响。在此，我们研究了RVVC对其他健康女性阴道粘膜的分子作用。研究方法：对患有RVVC的女性阴道组织活检进行基因表达分析，包括目前患有外阴阴道念珠菌病（VVC, n = 19）和感染之间的女性（培养阴性RVVC [CNR]， n = 8）；无症状感染白色念珠菌的女性（无症状[AS]， n = 7）；健康对照组（n = 18）。基因表达谱在组间进行比较，并与从问卷调查和妇科检查中获得的临床数据相关联。结果：在阴道活检中鉴定的20171个基因中，与健康对照组相比，RVVC组有6506个基因差异表达。基因表达通路分析揭示了RVVC与炎症反应通路之间的关联，特别是参与中性粒细胞募集和激活的基因。参与炎症和中性粒细胞募集的基因表达随着VVC临床严重程度的增加而增加，而一些参与上皮完整性的基因表达随着感染临床严重程度的增加而降低。CNR组和AS组的基因表达谱与健康对照组相当。结论：活动性感染期间RVVC的临床严重程度与阴道黏膜中参与分子炎症和中性粒细胞活化的基因表达增加有关。健康对照组和急性感染的裂谷病毒感染妇女之间没有差异，这表明在裂谷病毒感染组中观察到的分子效应仅在活动性感染期间存在。

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引用次数: 0

Role of Decidual Natural Killer Cells in the Pathogenesis of Preeclampsia 蜕膜自然杀伤细胞在子痫前期发病中的作用。

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2024-12-30 DOI: 10.1111/aji.70033

Shuang Yue, Jinlai Meng

Preeclampsia is one of the most severe obstetric complications, yet its pathogenesis remains unclear. Decidual natural killer (dNK) cells, the most abundant immune cells at the maternal-fetal interface, are closely associated with preeclampsia due to abnormalities in their quantity, phenotype, and function. This review summarizes the molecular mechanisms by which dNK cells regulate extravillous trophoblast (EVT) invasion, promote uterine spiral artery remodeling, and maintain immune tolerance. Furthermore, it explores how disruptions in these mechanisms and changes in the decidual microenvironment alter dNK cell properties, driving the progression of preeclampsia. Understanding the mechanisms of dNK cells and identifying potential therapeutic targets may provide new insights for clinical intervention.

先兆子痫是最严重的产科并发症之一，但其发病机制尚不清楚。蜕膜自然杀伤细胞（dNK）是母胎界面上最丰富的免疫细胞，由于其数量、表型和功能异常，与子痫前期密切相关。本文综述了dNK细胞调控上皮外滋养细胞（EVT）侵袭、促进子宫螺旋动脉重构、维持免疫耐受的分子机制。此外，它还探讨了这些机制的破坏和个体微环境的变化如何改变dNK细胞特性，从而推动先兆子痫的进展。了解dNK细胞的作用机制，确定潜在的治疗靶点，可能为临床干预提供新的见解。

引用次数: 0

Placentas From SARS-CoV-2 Infection During Pregnancy Exhibit Foci of Oxidative Stress and DNA Damage 妊娠期感染SARS-CoV-2的胎盘表现出氧化应激和DNA损伤的病灶。

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2024-12-30 DOI: 10.1111/aji.70034

Guilherme M. Nobrega PhD, Eliza R. McColl PhD, Arthur Antolini-Tavares MD, Renato T. Souza MD PhD, José Guilherme Cecatti MD PhD, Maria Laura Costa MD PhD, Indira U. Mysorekar PhD

Problem

COVID-19 during pregnancy is linked to increased maternal morbidity and a higher incidence of preterm births (PTBs), yet the underlying mechanisms remain unclear. Cellular senescence, characterized by the irreversible cessation of cell division, is a critical process in placental function, and its dysregulation has been implicated in pregnancy complications like PTB. Senescence can be induced by various stressors, including oxidative stress, DNA damage, and viral infections.

Method of Study

In this study, we determined whether COVID-19 had an impact on placental senescence. We examined placentas from women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 10 term, 4 preterm) compared to uninfected controls (n = 10 term, 3 preterm). The placentas were analyzed for SARS-CoV-2 infection (spike and nucleocapsid viral proteins), markers of DNA damage (γH2AX) and oxidative stress (ROS), and senescence (telomere length, cell cycle regulators, and senescence-associated secretory phenotype [SASP]).

Results

Although no overall differences in cellular senescence markers were observed between the COVID-19 positive and negative groups, we found increased secreted SASP markers. Confocal microscopy of placentas from COVID-19 positive cases revealed localized areas of oxidative stress and DNA damage colocalized with SARS-CoV-2 spike protein.

Conclusions

These findings indicate that SARS-CoV-2 infection induces localized focal placental damage, warranting further investigation into its impact on maternal and perinatal outcomes.

问题：妊娠期COVID-19与孕产妇发病率增加和早产发生率升高有关，但其潜在机制尚不清楚。细胞衰老以细胞分裂不可逆转的停止为特征，是胎盘功能的一个关键过程，其失调与妊娠并发症如PTB有关。衰老可由各种应激因素引起，包括氧化应激、DNA损伤和病毒感染。研究方法：在本研究中，我们确定COVID-19是否对胎盘衰老有影响。我们检测了感染严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）的妇女（n = 10个足月，4个早产）与未感染的对照组（n = 10个足月，3个早产）的胎盘。分析胎盘的SARS-CoV-2感染（刺突和核衣壳病毒蛋白）、DNA损伤标志物（γ - h2ax）和氧化应激（ROS），以及衰老（端粒长度、细胞周期调节因子和衰老相关分泌表型[SASP]）。结果：虽然细胞衰老标志物在COVID-19阳性和阴性组之间没有总体差异，但我们发现分泌的SASP标志物增加。来自COVID-19阳性病例的胎盘共聚焦显微镜显示，氧化应激和DNA损伤的局部区域与SARS-CoV-2刺突蛋白共定位。结论：这些发现表明，SARS-CoV-2感染可引起局部局灶性胎盘损伤，值得进一步研究其对孕产妇和围产期结局的影响。

{"title":"Placentas From SARS-CoV-2 Infection During Pregnancy Exhibit Foci of Oxidative Stress and DNA Damage","authors":"Guilherme M. Nobrega PhD, Eliza R. McColl PhD, Arthur Antolini-Tavares MD, Renato T. Souza MD PhD, José Guilherme Cecatti MD PhD, Maria Laura Costa MD PhD, Indira U. Mysorekar PhD","doi":"10.1111/aji.70034","DOIUrl":"10.1111/aji.70034","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>COVID-19 during pregnancy is linked to increased maternal morbidity and a higher incidence of preterm births (PTBs), yet the underlying mechanisms remain unclear. Cellular senescence, characterized by the irreversible cessation of cell division, is a critical process in placental function, and its dysregulation has been implicated in pregnancy complications like PTB. Senescence can be induced by various stressors, including oxidative stress, DNA damage, and viral infections.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>In this study, we determined whether COVID-19 had an impact on placental senescence. We examined placentas from women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (<i>n</i> = 10 term, 4 preterm) compared to uninfected controls (<i>n</i> = 10 term, 3 preterm). The placentas were analyzed for SARS-CoV-2 infection (spike and nucleocapsid viral proteins), markers of DNA damage (γH2AX) and oxidative stress (ROS), and senescence (telomere length, cell cycle regulators, and senescence-associated secretory phenotype [SASP]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Although no overall differences in cellular senescence markers were observed between the COVID-19 positive and negative groups, we found increased secreted SASP markers. Confocal microscopy of placentas from COVID-19 positive cases revealed localized areas of oxidative stress and DNA damage colocalized with SARS-CoV-2 spike protein.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings indicate that SARS-CoV-2 infection induces localized focal placental damage, warranting further investigation into its impact on maternal and perinatal outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909000","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

Role of the Systemic Immune-Inflammation Index and Systemic Immune-Response Index in the Prediction of Adverse Outcomes in Pregnant Women With Antiphospholipid Syndrome 全身免疫炎症指数和全身免疫反应指数在预测抗磷脂综合征孕妇不良结局中的作用

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2024-12-30 DOI: 10.1111/aji.70032

Şükran Doğru, Huriye Ezveci, Fikriye Karanfil Yaman, Ülfet Sena Metin, Ali Acar

Problem

This study aims to evaluate the role of the systemic immune-inflammation index (SII) and the systemic immune-response index (SIRI) in predicting adverse perinatal outcomes (APO) in pregnant women with antiphospholipid syndrome (APS).

Methods

This is a retrospective case–control study at the tertiary center, between January 2015 and January 2023. The study included APS cases and a low-risk control group. Pregnant women with APS (n = 52) and controls (n = 104) were compared between SII and SIRI values taken in the first trimester (1) and the last month before birth (2). It was examined whether these indexes predicted APO in cases with APS.

Results

In the APS group, SII and SIRI values taken in the first trimester (1) and in the last month before birth (2) were significantly lower than in the control group (p = 0.015, p = 0.023, p = 0.001, p = 0.001, respectively). The small for gestational age (SGA) rate was 30.8% and the stillbirth rate was 11.5% in the APS group (p = 0.017, p = 0.001). The optimum cutoff values for SGA were 584.97 (75% sensitivity, 77.8% specificity), 688.50 (62.5% sensitivity, 62.9% specificity), and 1.02 (56.3% sensitivity, 77.8% specificity) for SII 1, SII 2, and SIRI 1, respectively. The optimum cutoff value for stillbirth was 1.23 for SIRI 2 (83.3% sensitivity, 89.1% specificity, p = 0.004).

Conclusion

Pregnant women with APS had decreased blood indices in the first trimester and the last month before birth compared to the control group. In cases with APS, these indices can predict APOs like SGA and stillbirth.

问题：本研究旨在评估全身免疫炎症指数（SII）和全身免疫反应指数（SIRI）在预测抗磷脂综合征（APS）孕妇不良围产期结局（APO）中的作用。方法：2015年1月至2023年1月在三级中心进行回顾性病例对照研究。该研究包括APS病例和低风险对照组。将52名APS孕妇（n = 52）和104名对照组（n = 104）在妊娠早期(1)和出生前最后一个月(2)的SII和SIRI值进行比较。研究这些指标是否能预测APS患者的APO。结果：APS组孕早期(1)和出生前最后一个月(2)SII和SIRI值显著低于对照组（p = 0.015, p = 0.023, p = 0.001, p = 0.001）。APS组小胎龄（SGA）率为30.8%，死胎率为11.5% （p = 0.017, p = 0.001）。SII 1、SII 2和SIRI 1对SGA的最佳截止值分别为584.97（75%敏感性，77.8%特异性）、688.50（62.5%敏感性，62.9%特异性）和1.02（56.3%敏感性，77.8%特异性）。sire2诊断死产的最佳临界值为1.23（敏感性83.3%，特异性89.1%,p = 0.004）。结论：与对照组相比，APS孕妇在妊娠早期和出生前最后一个月的血液指标均有所下降。在APS病例中，这些指标可以预测SGA和死产等apo。

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引用次数: 0