American Journal of Reproductive Immunology最新文献_第4页

Cell Communications Between GCs and Macrophages Contribute to the Residence of Macrophage in Preovulatory Follicles GCs和巨噬细胞之间的细胞通讯有助于巨噬细胞在排卵前卵泡中驻留。

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2024-11-09 DOI: 10.1111/aji.70009

Huihua Wu, Ce Zhang, Rui Zhu, Qingxia Meng, Fuxin Wang, Liang Gao, Nannan Zhao, Hong Li, Mingqing Li

Problem

There were not only granulosa cells (GCs) but also immune cells in preovulatory follicular fluid. The objective of this study was to explore the interactions between macrophages and GCs via adhesion molecules in preovulatory follicles and the regulatory mechanisms of the interactions.

Method of Study

Flow cytometry and immunofluorescence were used to detect the expression of ITGB1 in macrophages and fibronectin (FN)1 in GCs in preovulatory follicles from 12 patients. The synthesis of FN1 protein in human ovarian GCs line (KGN) was detected by western blot. An adhesion experiment was performed to observe the changes of KGN cells adhesion to macrophages.

Results

The progesterone levels 12 h after human chorionic gonadotropin (HCG) administration in the high proportion immune cells (high immune [HI]) group were significantly higher than that in the low proportion immune cells (low immune [LI]) group (p < 0.0001). The expression of ITGB1 in macrophages in the HI group was higher than in the LI group. The expression of FN1 in GCs in HI group was higher than in LI group (p < 0.01). Progesterone increased the synthesis of FN1 in KGN cells (p < 0.0001) and was suppressed by the elimination of PGR. The adhesion effect of KGN cells on macrophages was enhanced by progesterone (p < 0.0001).

Conclusion

After luteinizing hormone (LH)/HCG surge, progesterone promotes the expression of FN1 in GCs by acting on the receptor PGR, and then GCs enhance the adhesion of macrophages by FN1-ITGB1 interaction, further leading to the result that macrophages perform diverse functional activities to maintain tissue homeostasis during ovulation.

问题：排卵前卵泡液中不仅有颗粒细胞（GCs），还有免疫细胞。本研究的目的是探讨巨噬细胞和 GCs 通过粘附分子在排卵前卵泡中的相互作用及其调控机制：研究方法：采用流式细胞术和免疫荧光法检测12名患者排卵前卵泡中巨噬细胞中ITGB1和GCs中纤维粘连蛋白（FN）1的表达。用 Western 印迹法检测了人卵巢 GCs 株系（KGN）中 FN1 蛋白的合成。通过粘附实验观察 KGN 细胞与巨噬细胞粘附的变化：结果：高比例免疫细胞（高免疫[HI]）组在注射人绒毛膜促性腺激素（HCG）12 h后的孕酮水平显著高于低比例免疫细胞（低免疫[LI]）组（P < 0.0001）。HI 组巨噬细胞中 ITGB1 的表达高于 LI 组。HI 组 GC 中 FN1 的表达高于 LI 组（P < 0.01）。黄体酮增加了KGN细胞中FN1的合成（p < 0.0001），并在去除PGR后被抑制。黄体酮增强了KGN细胞对巨噬细胞的粘附作用（p < 0.0001）：结论：黄体生成素（LH）/HCG激增后，黄体酮通过作用于受体PGR促进GCs中FN1的表达，然后GCs通过FN1-ITGB1的相互作用增强巨噬细胞的粘附性，进一步导致巨噬细胞在排卵期间进行多种功能活动以维持组织稳态。

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引用次数: 0

Immune Thrombocytopenic Purpura and Maternal and Neonatal Outcomes During Pregnancy: A Systematic Review and Meta-Analysis 妊娠期免疫性血小板减少性紫癜与孕产妇和新生儿结局：系统回顾和元分析》。

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2024-11-05 DOI: 10.1111/aji.70008

Hong Zhang, Lixia Shi, Hui Shang, Huili Yang

Immune thrombocytopenic purpura (ITP) affects 1–3 out of every 10 000 pregnancies, posing significant risks to both mothers and newborns. The condition often requires careful management to prevent severe hemorrhagic events. PubMed, Embase, Scopus, and Web of Science searched for relevant literature until June 2024. A meta-analysis was performed to evaluate the effect of ITP on maternal and fetal outcomes. The results showed that antepartum hemorrhage occurred in 0.17 (95% CI = 0.12–0.25) of patients and postpartum hemorrhage occurred in 0.11 (95% CI = 0.07–0.16) of pregnant women with ITP. About 0.63 (95% CI = 0.50–0.74) of pregnant women needed treatment for ITP. The cesarean section (CS) rate was 0.48 (95% CI = 0.34–0.61), and the occurrence of preterm labor was 0.14 (95% CI = 0.07–0.24). A total of 0.32 of neonates had thrombocytopenia (95% CI = 0.18–0.52). The difference between the platelet count of those diagnosed with ITP before pregnancy and those diagnosed after pregnancy was significant (MD = –31.50, 95% CI = 51.29–11.72, p < 0.01). This meta-analysis highlights the significant impact of ITP on pregnancy, estimating risks of bleeding, CS, gestational diabetes, preterm labor, and neonatal thrombocytopenia. These findings underscore the need for vigilant monitoring and tailored management of pregnant women with ITP.

免疫性血小板减少性紫癜（ITP）每 10 000 名孕妇中就有 1-3 人患病，对母亲和新生儿都有很大风险。这种疾病通常需要精心治疗，以防止严重出血事件的发生。PubMed、Embase、Scopus和Web of Science检索了截至2024年6月的相关文献。我们进行了一项荟萃分析，以评估 ITP 对产妇和胎儿预后的影响。结果显示，在ITP孕妇中，0.17（95% CI = 0.12-0.25）的患者会发生产前出血，0.11（95% CI = 0.07-0.16）的患者会发生产后出血。约有 0.63（95% CI = 0.50-0.74）名孕妇需要治疗 ITP。剖宫产率为 0.48（95% CI = 0.34-0.61），早产率为 0.14（95% CI = 0.07-0.24）。共有 0.32 名新生儿患有血小板减少症（95% CI = 0.18-0.52）。孕前诊断为 ITP 的新生儿和孕后诊断为 ITP 的新生儿的血小板计数差异显著（MD = -31.50，95% CI = 51.29-11.72，p＜0.05）。

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引用次数: 0

Pregnancy Outcomes in Grand Multiparity Women With Antiphospholipid Antibodies 患有抗磷脂抗体的大龄多产妇的妊娠结局。

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2024-10-30 DOI: 10.1111/aji.70013

Keren Zloto, Shani Steinberg, Shir Lev, Rakefet Yoeli-Ullman, Stanley Niznik, Nancy Agmon-Levin, Keren Ofir

Objective

In recent years antiphospholipid syndrome (APS) as well as antiphospholipid antibodies (aPL) prevalence has demonstrated an upward trend in women during reproductive age. There is a lack of data concerning its effects on women with grand multiparity (GMP) (parity ≥5). Hence, this study aimed to assess pregnancy outcomes among GMP aPL/APS patients.

Study Design

We retrospectively assembled the births of GMP women with aPL/APS, between 2017 and 2022 in the Sheba Medical Center. We compared their deliveries with those of two control groups: (1) the “aPL/APS-controls”—of pregnant women with aPL/APS and parity <5. (2) The “GMP-controls”- parity ≥5 without aPL/APS. We examined demographics, aPL characteristics, pregnancy, and neonatal outcomes between the groups.

Results

In total, 42 deliveries in the study group were compared to 461 deliveries in the “aPL/APS-controls” group and 84 deliveries of the “GMP-controls.” Most parameters were similar across groups. However, the study group had a higher rate of obstetric APS diagnosis (64.64% vs. 83.33%, p < 0.01) and showed significant differences such as older maternal age, higher BMI, more polyhydramnios cases, and larger babies compared to controls (33.91 vs. 36.19, p = 0.05; 23.2 vs. 28.89, p = 0.02; 3.68 vs. 11.9, p = 0.01; and 2.17 vs. 14.28, p < 0.01, respectively).

Conclusions

Our findings reveal that perinatal outcomes in aPL/APS GMP women are comparable and not inferior to those in aPL/APS women with <5 pregnancies or in comparison to the general GMP population. The minor differences observed may all be related to GMP women's older age and higher BMI.

目的：近年来，抗磷脂综合征（APS）和抗磷脂抗体（aPL）在育龄妇女中的发病率呈上升趋势。目前还缺乏有关抗磷脂综合征对多胎妊娠（GMP）（胎次≥5）妇女影响的数据。因此，本研究旨在评估GMP aPL/APS患者的妊娠结局：我们回顾性地收集了 2017 年至 2022 年期间在谢巴医疗中心分娩的 GMP aPL/APS 妇女的分娩情况。我们将她们的分娩情况与两个对照组的分娩情况进行了比较：（1）"aPL/APS-对照组"--aPL/APS孕妇和奇数结果：研究组的 42 例分娩与 "aPL/APS-对照组 "的 461 例分娩和 "GMP-对照组 "的 84 例分娩进行了比较。各组的大多数参数相似。然而，研究组的产科 APS 诊断率更高（64.64% 对 83.33%，P 结论：研究组的产科 APS 诊断率更高：我们的研究结果表明，患有 aPL/APS 的 GMP 孕妇的围产期结果与患有 aPL/APS 的 GMP 孕妇相当，并不逊色于患有 aPL/APS 的 GMP 孕妇。

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引用次数: 0

Vaginal Microbiome and the Risk of Preterm Birth in Women Living With HIV: A Scoping Review 感染 HIV 的妇女的阴道微生物群与早产风险：范围界定综述》。

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2024-10-30 DOI: 10.1111/aji.70011

Fouzia Zahid Ali Khan, Saifuddin Ahmed, Anna Maya Powell

There are sparse data on the role of the vaginal microbiome (VMB) in pregnancy among pregnant women living with HIV (PWLWH) and its association with spontaneous preterm birth (sPTB). We conducted a scoping review to assess associations between vaginal microbiota and sPTB among PWLWH. Three studies were included, representing a total of 180 PWLWH out of 652 total pregnancies. All studies used modern DNA sequencing methods (16S rRNA amplification, metagenomics, or metatranscriptomics). PWLWH had higher VMB richness and diversity compared to HIV-uninfected pregnant women and higher sPTB rates in two of three studies. A higher proportion of sPTB among PWLWH was observed in those with Lactobacillus-deficient, anaerobe-dominant vaginal microbiota. In two of three studies, higher concentrations of vaginal inflammation markers were associated with increased VMB richness and diversity. HIV status was independently associated with sPTB. It is unclear if increased vaginal microbial diversity among PWLWH or increased vaginal inflammation contributes more to PTB, but HIV does appear to alter the VMB in pregnant individuals and may also affect PTB rates in microbiome-independent pathways. Given the limited number of studies, heterogeneity in sample size, sample collection methods, and inconsistent results it is difficult to causally link HIV, VMB, inflammatory cytokines, and sPTB.

关于感染艾滋病病毒的孕妇（PWLWH）的阴道微生物群（VMB）在妊娠期的作用及其与自发性早产（sPTB）的关系的数据很少。我们进行了一次范围界定综述，以评估感染艾滋病病毒的孕妇阴道微生物群与自发性早产（sPTB）之间的关系。共纳入了三项研究，代表了 652 名孕妇中的 180 名低龄孕妇。所有研究都采用了现代 DNA 测序方法（16S rRNA 扩增、元基因组学或元转录组学）。与未感染 HIV 的孕妇相比，PWLWH 的 VMB 丰富度和多样性更高，在三项研究中的两项研究中，PWLWH 的 sPTB 感染率更高。在乳酸杆菌缺乏、厌氧菌占主导地位的阴道微生物群中，PWLWH 感染 sPTB 的比例较高。在三项研究中的两项研究中，阴道炎症标志物浓度较高与阴道微生物丰富度和多样性增加有关。艾滋病病毒感染状态与 sPTB 存在独立关联。目前还不清楚是PWLWH阴道微生物多样性的增加还是阴道炎症的增加更容易导致PTB，但HIV似乎确实改变了孕妇的VMB，也可能通过与微生物无关的途径影响PTB的发病率。鉴于研究数量有限、样本大小不一、样本收集方法不同以及结果不一致，很难将 HIV、VMB、炎症细胞因子和 sPTB 建立因果关系。

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引用次数: 0

SR-16234, a Unique Selective Estrogen Receptor Modulator, Suppressed Proliferation and Pain-Related Factor Expression by Inhibition of the Nuclear Factor-kappa B Pathway in Endometriotic Stromal Cells SR-16234是一种独特的选择性雌激素受体调节剂，它通过抑制子宫内膜异位基质细胞的核因子-kappa B通路来抑制其增殖和疼痛相关因子的表达。

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2024-10-30 DOI: 10.1111/aji.70010

Emiko Yamane, Yukihiro Azuma, Mei Matsumoto, Eri Sato, Yoshiaki Ota, Tasuku Harada, Fuminori Taniguchi

Problem

What is the effect of SR-16234 (SR), a selective estrogen receptor (ER) modulator, on human endometriotic stromal cells (ESCs)?

Method of Study

Endometriotic tissues were obtained from 21 patients undergoing laparoscopic surgery for ovarian endometriomas (OEs). Normal eutopic endometrium during the luteal phase was obtained from 18 patients without endometriosis. ESCs isolated from OEs and normal eutopic endometrial stromal cells (NESCs) were cultured with SR and subsequently exposed to tumor necrosis factor (TNF)-α. After 48 h of incubation, the effect of SR on cell proliferation was evaluated by the WST-8 assay. The gene expressions of inflammatory and pain-related factors, including interleukin (IL)-6, IL-8, cyclooxygenase (COX)-2, transient receptor potential vanilloid (TRPV)1, ESR1, and ESR2, were evaluated by real-time RT-PCR. The phosphorylation of Inhibitor κBα (IκBα), extracellular signal-regulated kinase (ERK)1/2, and Protein Kinase B (AKT) were evaluated by western blot analysis. ILs, prostaglandin (PG) E2, and intranuclear p65 syntheses were assessed by ELISA.

Results

SR treatment repressed TNF-α-induced proliferation by 20% in ESCs but not　NESCs. SR also reduced IL-6, IL-8, COX-2, TRPV1, ESR1, and ESR2 mRNA expressions and ILs protein, and PGE2 synthesis in ESCs, whereas in NESCs, only TRPV1 mRNA expression was decreased. SR suppressed TNF-α-induced phosphorylated IκBα levels by approximately 50%, and intranuclear p65 protein was reduced by 30% compared to addition of only TNF-α in ESCs. However, SR did not affect the phosphorylation of AKT and ERK1/2.

Conclusions

SR appears to be a potential therapeutic agent for endometriosis by suppressing inflammatory and pain-related factor expressions by inhibiting the nuclear factor-kappa B pathway.

问题：SR-16234（SR）是一种选择性雌激素受体（ER）调节剂，它对人类子宫内膜异位基质细胞（ESC）有什么影响？从21名接受腹腔镜手术治疗卵巢子宫内膜异位症（OEs）的患者身上获取子宫内膜组织。从 18 名无子宫内膜异位症的患者身上获取黄体期的正常异位子宫内膜。用SR培养从OEs和正常异位子宫内膜基质细胞（NESCs）中分离出来的ESCs，然后将其暴露于肿瘤坏死因子（TNF）-α。培养 48 小时后，用 WST-8 试验评估了 SR 对细胞增殖的影响。实时 RT-PCR 评估了炎症和疼痛相关因子的基因表达，包括白细胞介素 (IL)-6、IL-8、环氧化酶 (COX)-2、瞬时受体位点类香草素 (TRPV)1、ESR1 和 ESR2。蛋白印迹分析评估了抑制因子κBα（IκBα）、细胞外信号调节激酶（ERK）1/2 和蛋白激酶 B（AKT）的磷酸化情况。通过酶联免疫吸附分析评估了ILs、前列腺素（PG）E2和核内p65的合成：结果：SR处理可抑制TNF-α诱导的ESCs增殖20%，但不能抑制NESCs。SR还降低了ESCs中IL-6、IL-8、COX-2、TRPV1、ESR1和ESR2 mRNA的表达以及ILs蛋白和PGE2的合成，而在NESCs中仅降低了TRPV1 mRNA的表达。与仅添加 TNF-α 相比，SR 可抑制 TNF-α 诱导的磷酸化 IκBα 水平约 50%，核内 p65 蛋白减少 30%。然而，SR 并不影响 AKT 和 ERK1/2 的磷酸化：SR通过抑制核因子-kappa B通路抑制炎症和疼痛相关因子的表达，似乎是子宫内膜异位症的潜在治疗药物。

{"title":"SR-16234, a Unique Selective Estrogen Receptor Modulator, Suppressed Proliferation and Pain-Related Factor Expression by Inhibition of the Nuclear Factor-kappa B Pathway in Endometriotic Stromal Cells","authors":"Emiko Yamane, Yukihiro Azuma, Mei Matsumoto, Eri Sato, Yoshiaki Ota, Tasuku Harada, Fuminori Taniguchi","doi":"10.1111/aji.70010","DOIUrl":"10.1111/aji.70010","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>What is the effect of SR-16234 (SR), a selective estrogen receptor (ER) modulator, on human endometriotic stromal cells (ESCs)?</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Endometriotic tissues were obtained from 21 patients undergoing laparoscopic surgery for ovarian endometriomas (OEs). Normal eutopic endometrium during the luteal phase was obtained from 18 patients without endometriosis. ESCs isolated from OEs and normal eutopic endometrial stromal cells (NESCs) were cultured with SR and subsequently exposed to tumor necrosis factor (TNF)-α. After 48 h of incubation, the effect of SR on cell proliferation was evaluated by the WST-8 assay. The gene expressions of inflammatory and pain-related factors, including <i>interleukin</i> (<i>IL</i>)<i>-6</i>, <i>IL-8</i>, <i>cyclooxygenase</i> (<i>COX</i>)<i>-2</i>, <i>transient receptor potential vanilloid</i> (<i>TRPV</i>)<i>1</i>, <i>ESR1</i>, and <i>ESR2</i>, were evaluated by real-time RT-PCR. The phosphorylation of Inhibitor κBα (IκBα), extracellular signal-regulated kinase (ERK)1/2, and Protein Kinase B (AKT) were evaluated by western blot analysis. ILs, prostaglandin (PG) E2, and intranuclear p65 syntheses were assessed by ELISA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SR treatment repressed TNF-α-induced proliferation by 20% in ESCs but not　NESCs. SR also reduced <i>IL-6</i>, <i>IL-8</i>, <i>COX-2</i>, <i>TRPV1</i>, <i>ESR1</i>, and <i>ESR2</i> mRNA expressions and ILs protein, and PGE2 synthesis in ESCs, whereas in NESCs, only <i>TRPV1</i> mRNA expression was decreased. SR suppressed TNF-α-induced phosphorylated IκBα levels by approximately 50%, and intranuclear p65 protein was reduced by 30% compared to addition of only TNF-α in ESCs. However, SR did not affect the phosphorylation of AKT and ERK1/2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SR appears to be a potential therapeutic agent for endometriosis by suppressing inflammatory and pain-related factor expressions by inhibiting the nuclear factor-kappa B pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543077","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

Altered Endometrial Microbiota Profile Is Associated With Poor Endometrial Receptivity of Repeated Implantation Failure 子宫内膜微生物群谱系改变与反复种植失败的子宫内膜接受能力差有关

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2024-10-29 DOI: 10.1111/aji.70005

Rongxue Zhang, Miaomiao Wang, Jixiang Zhong, Huiying Xue

Purpose

To gain insight into the endometrial pathophysiology of unexplained repeated implantation failure (RIF), we examined the characteristics of genital tract microbiota and explored the correlation between the microbiota and endometrial receptivity.

Methods

Vaginal secretion (VS) and endometrial biopsy (EB) samples were collected from patients with RIF (RIF group, n = 32) and those with infertility who had achieved pregnancy during their initial embryo transfer cycle (control group, n = 18). 16S ribosomal RNA sequencing and quantitative PCR were performed to characterize the microbiota of the two groups. Spearman's correlation analysis was performed to determine the relationship between endometrial receptivity markers and endometrial microbiota.

Results

Endometrial microbiota exhibited distinct characteristics from vaginal microbiota, with a higher alpha-diversity. Alpha-diversity of the endometrial microbiota was higher in the RIF group than in the control group. Compared with the control group, the RIF group had a significant decrease in endometrial Lactobacillus abundance and an increase in Gardnerella and Acinetobacter abundances. The expression levels of endometrial receptivity markers, including homeobox A11, integrin αvβ3, leukemia inhibitor factor, matrix metalloproteinase-9, and vascular endothelial growth factor, were lower in the RIF group than in the control group. Moreover, the expression levels of these markers were correlated with endometrial Lactobacillus, Gardnerella, and Acinetobacter abundances.

Conclusion

RIF is characterized by endometrial microbiota dysbiosis and poor endometrial receptivity. Moreover, abnormal endometrial microbiota is associated with impaired endometrial receptivity, which may be a potential cause of unexplained RIF.

目的：为了深入了解原因不明的反复植入失败（RIF）的子宫内膜病理生理学，我们研究了生殖道微生物群的特征，并探讨了微生物群与子宫内膜接受性之间的相关性：阴道分泌物（VS）和子宫内膜活检（EB）样本分别取自RIF患者（RIF组，n = 32）和在首次胚胎移植周期中妊娠的不孕症患者（对照组，n = 18）。通过 16S 核糖体 RNA 测序和定量 PCR 分析两组患者的微生物群特征。进行斯皮尔曼相关性分析以确定子宫内膜受孕标志物与子宫内膜微生物群之间的关系：结果：子宫内膜微生物群表现出与阴道微生物群不同的特征，α-多样性更高。RIF 组子宫内膜微生物群的α-多样性高于对照组。与对照组相比，RIF 组的子宫内膜乳酸杆菌数量显著减少，而加德纳菌和醋氨曲霉菌数量增加。RIF组子宫内膜接受性标志物的表达水平低于对照组，包括同种异体A11、整合素αvβ3、白血病抑制因子、基质金属蛋白酶-9和血管内皮生长因子。此外，这些标记物的表达水平与子宫内膜乳酸杆菌、加德纳菌和醋酐菌的数量相关：结论：RIF 的特点是子宫内膜微生物群失调和子宫内膜接受能力差。结论：RIF 的特点是子宫内膜微生物群失调和子宫内膜接受能力差，而且子宫内膜微生物群异常与子宫内膜接受能力受损有关，这可能是导致原因不明的 RIF 的潜在原因。

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引用次数: 0

Analysis of Pregnancy Outcomes in Patients Exhibiting Recurrent Miscarriage With Concurrent Low-Titer Antiphospholipid Antibodies 并发低滴度抗磷脂抗体的复发性流产患者的妊娠结局分析

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2024-10-29 DOI: 10.1111/aji.13940

Yuxin Chen, Wenchao Xu, Shuang Huang, Juanli Li, Ting Li, Jian Chen, Yu Lu, Jianyu Zhang

<div> <section> <h3> Background</h3> <p>Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombotic events and adverse pregnancy outcomes, often associated with elevated antiphospholipid antibodies (aPLs). The 2023 ACR/EULAR criteria for APS necessitate persistent medium to high titers of aPLs for laboratory confirmation. However, the impact of persistently low-titer aPLs in recurrent miscarriage (RM) patients remains controversial. This study aims to analyze the effect of treatment on pregnancy outcomes and maternal–fetal complications in patients with low-titer aPLs.</p> </section> <section> <h3> Methods</h3> <p>The study encompassed 252 pregnancies in 237 RM patients tested for aPLs at the Third Hospital of Guangzhou Medical University from January 2018 to July 2022. Patients were divided into two groups based on aPLs titers: 86 with low-titer aPLs (92 pregnancies) and 151 aPLs-negative (160 pregnancies). Of the low-titer group, 71 received treatment, while 21 and all aPLs-negative patients did not. Seventy-one treated patients with low-titer aPLs were divided into two groups. Group A (<i>n</i> = 15) received a standard treatment regimen that included low-dose aspirin (LDA) and low-molecular-weight heparin (LMWH). In contrast, Group B (<i>n</i> = 56) received a multidrug regimen, which included hydroxychloroquine (HCQ) and/or glucocorticoids (GC) and/or intravenous immunoglobulin (IVIG) in addition to the standard treatment of LDA and LMWH. Pregnancy outcomes and maternal–fetal complications were subsequently compared.</p> </section> <section> <h3> Results</h3> <p>The highest positivity rates were for aCL-IgM (76.2% in the untreated low-titer aPLs group and 81.7% in the treated low-titer aPLs group), followed by aβ2GPI-IgM (23.8% in the untreated low-titer aPL group and 11.4% in the treated low-titer aPLs group), and LA (5.6% in the untreated low-titer aPLs group and 3.3% in the treated low-titer aPLs group). Single antibody positivity was 90.5% in the untreated low-titer aPL group and 87.3% in the treated low-titer aPLs group, with double positivity at 9.5% in the untreated low-titer aPLs group and 12.7% in the treated low-titer aPLs group. No triple positivity was detected. The treated low-titer aPLs group had more previous miscarriages (<i>p</i> < 0.05) and a higher ANA positivity rate (<i>p</i> < 0.05) than the aPLs-negative group. Additionally, the treated low-titer aPLs group had lower complement levels than the aPLs-negative group. Immunoglobulin IgM levels were higher in both the untreated and treated low-titer aPL groups compared to the aPLs-negative group (<i>p</i> < 0.05). Post treatment, the live bi

背景：抗磷脂综合征（APS）是一种以血栓事件和不良妊娠结局为特征的自身免疫性疾病，通常与抗磷脂抗体（aPL）升高有关。根据 2023 年 ACR/EULAR 的 APS 标准，需要持续的中高滴度 aPLs 才能进行实验室确认。然而，持续低滴度的抗磷脂抗体对复发性流产（RM）患者的影响仍存在争议。本研究旨在分析低滴度 aPLs 患者的治疗对妊娠结局和母胎并发症的影响：研究涵盖了2018年1月至2022年7月在广州医科大学附属第三医院接受aPLs检测的237例RM患者中的252例妊娠。根据 aPLs 滴度将患者分为两组：86 例 aPLs 低滴度患者（92 例妊娠）和 151 例 aPLs 阴性患者（160 例妊娠）。在低滴度组中，71 人接受了治疗，21 人和所有 aPLs 阴性患者没有接受治疗。71 名接受治疗的 aPL 低滴度患者被分为两组。A 组（n = 15）接受标准治疗方案，包括低剂量阿司匹林（LDA）和低分子量肝素（LMWH）。相比之下，B组（n = 56）接受了多种药物治疗方案，除了LDA和LMWH的标准治疗方案外，还包括羟氯喹（HCQ）和/或糖皮质激素（GC）和/或静脉注射免疫球蛋白（IVIG）。随后对妊娠结局和母胎并发症进行了比较：阳性率最高的是 aCL-IgM（未经治疗的低滴度 aPLs 组为 76.2%，经治疗的低滴度 aPLs 组为 81.7%），其次是 aβ2GPI-IgM（未经治疗的低滴度 aPLs 组为 23.8%，经治疗的低滴度 aPLs 组为 11.4%）和 LA（未经治疗的低滴度 aPLs 组为 5.6%，经治疗的低滴度 aPLs 组为 3.3%）。未经处理的低滴度 aPLs 组的单抗体阳性率为 90.5%，经处理的低滴度 aPLs 组为 87.3%；未经处理的低滴度 aPLs 组的双抗体阳性率为 9.5%，经处理的低滴度 aPLs 组为 12.7%。未发现三重阳性。与 aPLs 阴性组相比，接受治疗的低滴度 aPLs 组流产次数更多（P < 0.05），ANA 阳性率更高（P < 0.05）。此外，低滴度 aPLs 治疗组的补体水平低于 aPLs 阴性组。与 aPLs 阴性组相比，未治疗组和治疗低滴度 aPLs 组的免疫球蛋白 IgM 水平都更高（p < 0.05）。治疗后，低滴度组的活产率明显高于未治疗组（67.6% vs. 33.3%; p = 0.005）。与 aPLs 阴性患者相比，未经治疗的低滴度患者的流产率明显较低（32.4% 对 66.7%；P = 0.005）。在母体或胎儿并发症方面，两组间未发现明显差异。标准治疗组（A 组）有 8 例（53.3%）活产，而多药治疗组（B 组）有 40 例（71.4%）活产，活产率明显高于标准治疗组，但差异无统计学意义：研究表明，与 aPLs 阴性 RM 组相比，未经治疗的 aPLs 低滴度阳性 RM 患者的流产复发率更高。然而，在采取适当干预措施后，复发率会明显降低，这表明低滴度 aPLs 阳性 RM 患者接受治疗是有益的。

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引用次数: 0

Protein Modifications During Early Embryo Development 胚胎早期发育过程中的蛋白质修饰

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2024-10-26 DOI: 10.1111/aji.70007

Le Zhang, Yanbing Zhang, Hailong Sun

Background

Infertility is a global reproductive health burden. Assisted reproductive technologies (ARTs) have been widely used to help patients become pregnant. Few embryos develop to the blastocyst stage with ARTs, leading to relatively low live birth rates. Protein modifications play crucial roles in nearly every aspect of cell biology, including reproductive processes. The aim of this study was to explore the characteristics of protein modifications during embryonic development.

Methods

Proteomic data from humans and mice were acquired from the integrated proteome resources (iProX) of ProteomeXchange (PXD024267) and a tandem mass tag (TMT)-mass spectrometry dataset. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied for functional annotation. Protein–protein interactions (PPIs) of the modification-related genes were revealed by the STRING database. Modified proteins during mouse embryogenesis were visualized through heatmaps of hierarchically clustering using k-means.

Results

We identified modification-related proteins in human embryo development and characterized them through heatmaps, GO analysis, KEGG analysis, and PPI network analysis. We found that the 4-cell stage to the 8-cell stage might be the demarcation period for modification-related protein expression patterns during embryo development. Using quantitative mass spectrometry, we elucidated the methylation, acetylation, and ubiquitination events that occur during mouse embryogenesis to validate our findings in human embryonic development to some extent.

Conclusions

The results of our study suggest that the posttranslational modifications (PTMs) of human preimplantation embryos might exhibit the same trends as those in mice to exert synergistic and fine-tuned regulatory effects during embryonic development.

背景：不孕症是全球生殖健康的一大负担。辅助生殖技术（ART）已被广泛用于帮助患者怀孕。使用辅助生殖技术的胚胎很少发育到囊胚阶段，导致活产率相对较低。蛋白质修饰在细胞生物学的几乎每个方面都起着至关重要的作用，包括生殖过程。本研究旨在探索胚胎发育过程中蛋白质修饰的特点：方法：从 ProteomeXchange（PXD024267）的综合蛋白质组资源（iProX）和串联质量标签（TMT）质谱数据集中获得了人类和小鼠的蛋白质组数据。基因本体（GO）分析和京都基因组百科全书（KEGG）分析被用于功能注释。STRING数据库揭示了修饰相关基因的蛋白-蛋白相互作用（PPIs）。小鼠胚胎发生过程中的修饰蛋白通过使用k-means进行分层聚类的热图可视化：我们发现了人类胚胎发育过程中与修饰相关的蛋白质，并通过热图、GO分析、KEGG分析和PPI网络分析对其进行了表征。我们发现，4细胞期到8细胞期可能是胚胎发育过程中修饰相关蛋白表达模式的分界期。通过定量质谱分析，我们阐明了小鼠胚胎发育过程中发生的甲基化、乙酰化和泛素化事件，从而在一定程度上验证了我们在人类胚胎发育过程中的发现：我们的研究结果表明，人类植入前胚胎的翻译后修饰（PTMs）可能会表现出与小鼠相同的趋势，在胚胎发育过程中发挥协同和微调的调控作用。

{"title":"Protein Modifications During Early Embryo Development","authors":"Le Zhang, Yanbing Zhang, Hailong Sun","doi":"10.1111/aji.70007","DOIUrl":"10.1111/aji.70007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Infertility is a global reproductive health burden. Assisted reproductive technologies (ARTs) have been widely used to help patients become pregnant. Few embryos develop to the blastocyst stage with ARTs, leading to relatively low live birth rates. Protein modifications play crucial roles in nearly every aspect of cell biology, including reproductive processes. The aim of this study was to explore the characteristics of protein modifications during embryonic development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Proteomic data from humans and mice were acquired from the integrated proteome resources (iProX) of ProteomeXchange (PXD024267) and a tandem mass tag (TMT)-mass spectrometry dataset. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied for functional annotation. Protein–protein interactions (PPIs) of the modification-related genes were revealed by the STRING database. Modified proteins during mouse embryogenesis were visualized through heatmaps of hierarchically clustering using k-means.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified modification-related proteins in human embryo development and characterized them through heatmaps, GO analysis, KEGG analysis, and PPI network analysis. We found that the 4-cell stage to the 8-cell stage might be the demarcation period for modification-related protein expression patterns during embryo development. Using quantitative mass spectrometry, we elucidated the methylation, acetylation, and ubiquitination events that occur during mouse embryogenesis to validate our findings in human embryonic development to some extent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results of our study suggest that the posttranslational modifications (PTMs) of human preimplantation embryos might exhibit the same trends as those in mice to exert synergistic and fine-tuned regulatory effects during embryonic development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493012","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

Autoimmune Condition Diagnosis Following Recurrent Pregnancy Loss 复发性妊娠失败后的自身免疫疾病诊断。

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2024-10-26 DOI: 10.1111/aji.70006

Marisa R. Imbroane, Felicia LeMoine, Kelly S. Gibson

Problem

Research has suggested a link between recurrent pregnancy loss (RPL) and cell-mediated immunity dysregulation. We aimed to determine if a history of RPL is associated with diagnosis of a cell-mediated autoimmune condition (AIC).

Method of Study

A retrospective cohort study was conducted using the TriNetX research network. The RPL group had ≥3 spontaneous or missed abortions. Controls had at least one pregnancy but no diagnosis of RPL. Propensity score matching was used for age, race, and ethnicity. Z-test and relative risk analysis investigated the relationship between RPL and subsequent AIC diagnoses.

Results

One hundred twenty-eight thousand three hundred seventy-six patients were included in each cohort. RPL was associated with an increased risk for an AIC composite (RR 1.60, 95% CI [1.51, 1.69]), Crohn's disease, Graves’ disease, Hashimoto's thyroiditis, multiple sclerosis, rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, and ulcerative colitis, but not psoriatic arthritis.

Conclusions

Using a large research database of patients with RPL, we were able to demonstrate that an antecedent diagnosis of RPL is associated with increased risk of subsequent diagnosis of an AIC, often between 1 and 10 years after RPL.

问题研究表明，反复妊娠失败（RPL）与细胞介导的免疫失调之间存在联系。我们旨在确定RPL病史是否与细胞介导的自身免疫性疾病（AIC）的诊断有关：研究方法：我们利用 TriNetX 研究网络进行了一项回顾性队列研究。RPL组有≥3次自然流产或漏流产。对照组至少有一次妊娠，但未确诊为 RPL。对年龄、种族和民族采用倾向得分匹配法。Z检验和相对风险分析研究了RPL与随后的AIC诊断之间的关系：每个队列共纳入 12.8376 万名患者。RPL与AIC综合征（RR 1.60，95% CI [1.51，1.69]）、克罗恩病、格雷夫斯病、桥本氏甲状腺炎、多发性硬化症、类风湿性关节炎、Sjogren综合征、系统性红斑狼疮和溃疡性结肠炎的风险增加有关，但与银屑病关节炎无关：通过使用一个大型的 RPL 患者研究数据库，我们能够证明 RPL 的先兆诊断与 AIC 的后续诊断风险增加有关，这种风险通常发生在 RPL 后的 1 到 10 年之间。

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引用次数: 0

Scoping Review of Microbiota Dysbiosis and Risk of Preeclampsia 微生物群失调与先兆子痫风险的范围界定综述。

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology

Pub Date : 2024-10-23 DOI: 10.1111/aji.70003

Madeleine M. Jordan, Emmanuel Amabebe, Kamil Khanipov, Brandie DePaoli Taylor

Limited studies have investigated the role of the microbiota in hypertensive disorders of pregnancy (HDP), particularly preeclampsia, which often results in preterm birth. We evaluated 23 studies that explored the relationship between gut, vaginal, oral, or placental microbiotas and HDP. Scopus, ProQuest Health Research Premium Collection, ProQuest Nursing & Allied Health Database, EBSCO, and Ovid were searched for relevant literature. Majority (18) of studies focused on the gut microbiota, and far fewer examined the oral cavity (3), vagina (3), and placenta (1). One study examined the gut, oral, and vaginal microbiotas. The consensus highlights a potential role for microbiota dysbiosis in preeclampsia and HDP. Especially in the third trimester, preeclampsia is associated with gut dysbiosis—deficient in beneficial species of Akkermansia, Bifidobacterium, and Coprococcus but enriched with pathogenic Campylobacterota and Candidatus Saccharibacteria, with low community α-diversity. Similarly, the preeclamptic vaginal and oral microbiotas are enriched with bacterial vaginosis and periodontal disease-associated species, respectively. The trend is also observed in the placenta, which is colonized by gastrointestinal, respiratory tract, and periodontitis-related pathogens. Consequently, a chronic proinflammatory state that adversely impacts placentation is implicated. These observations however require more mechanistic studies to establish the timing of the preceding immune dysfunction and any causality.

关于微生物群在妊娠高血压疾病（HDP）中的作用，尤其是经常导致早产的先兆子痫中的作用的研究很有限。我们评估了 23 项探讨肠道、阴道、口腔或胎盘微生物群与 HDP 之间关系的研究。我们检索了 Scopus、ProQuest Health Research Premium Collection、ProQuest Nursing & Allied Health Database、EBSCO 和 Ovid，以查找相关文献。大多数研究（18 项）侧重于肠道微生物群，而研究口腔（3 项）、阴道（3 项）和胎盘（1 项）的研究则少得多。有一项研究考察了肠道、口腔和阴道微生物群。共识强调了微生物群失调在子痫前期和 HDP 中的潜在作用。特别是在妊娠三个月时，子痫前期与肠道菌群失调有关--缺乏有益的 Akkermansia、双歧杆菌和 Coprococcus，但富含致病的弯曲杆菌和酵母菌，群落 α-多样性较低。同样，先兆子痫患者的阴道和口腔微生物群分别富含细菌性阴道病和牙周病相关物种。在胎盘中也观察到了这种趋势，胎盘中定植有胃肠道、呼吸道和牙周炎相关病原体。因此，慢性促炎状态会对胎盘产生不利影响。然而，这些观察结果需要更多的机理研究，以确定之前免疫功能紊乱的时间和任何因果关系。

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引用次数: 0