Chronic endometritis (CE) is a frequent pathological condition that is defined as localized inflammation in the endometrium. Some adverse fertility consequences such as recurrent miscarriage and failure of implantation are associated with chronic endometritis. On the one hand, inflammation plays an important role in the pathogenesis of endometritis, and on the other hand, the role of viral infections in inducing inflammation can make this review strongly attractive and practical. We set out to provide an overview of viral infections as a potential etiology of CE pathophysiology through the alteration of an endometrial microenvironment and its association with infertility. To the best of our knowledge, this is the first review to demonstrate the role of viral infection in chronic endometritis, and whether or not infection ultimately plays a role..
慢性子宫内膜炎（CE）是一种常见的病理状态，被定义为子宫内膜的局部炎症。慢性子宫内膜炎会导致一些不良生育后果，如反复流产和植入失败。一方面，炎症在子宫内膜炎的发病机制中起着重要作用，另一方面，病毒感染在诱发炎症中的作用也使这一综述具有很强的吸引力和实用性。我们旨在通过子宫内膜微环境的改变及其与不孕症的关联，概述病毒感染作为 CE 病理生理学的潜在病因。据我们所知，这是第一篇综述性文章，论证了病毒感染在慢性子宫内膜炎中的作用，以及感染最终是否起作用。
{"title":"Viral Infection in Endometritis: Is There an Important Role or Not?","authors":"Hatav Ghasemi Tehrani, Marzieh Rezaei, Ferdous Mehrabian, Elham Naghshineh, Mohsen Moghoofei","doi":"10.1111/aji.13930","DOIUrl":"10.1111/aji.13930","url":null,"abstract":"<div>\u0000 \u0000 <p>Chronic endometritis (CE) is a frequent pathological condition that is defined as localized inflammation in the endometrium. Some adverse fertility consequences such as recurrent miscarriage and failure of implantation are associated with chronic endometritis. On the one hand, inflammation plays an important role in the pathogenesis of endometritis, and on the other hand, the role of viral infections in inducing inflammation can make this review strongly attractive and practical. We set out to provide an overview of viral infections as a potential etiology of CE pathophysiology through the alteration of an endometrial microenvironment and its association with infertility. To the best of our knowledge, this is the first review to demonstrate the role of viral infection in chronic endometritis, and whether or not infection ultimately plays a role..</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255414","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}
Eleanor Capozzi, Jason Daniels, Hani Mohamed, Fernando Cabezas Mejia, David Sternberg, Jennifer Bouey, Mimi Ghosh
Problem
Female sex workers (FSW) experience a disproportionately high burden of HIV infection, yet characterization of the vaginal immune microenvironment that may impact biological risk is not well studied among FSW in the United States. Additionally, feasible methodology for collecting biological materials has not been evaluated in this population.
Methods
We enrolled 10 FSW (5 premenopausal, 5 postmenopausal) who participated in a survey and provided vaginal swabs. Biomarkers were assessed by ELISA, and included cytokines, chemokines, and antimicrobial/wound-healing mediators.
Results
One hundred percent of FSW were African American, with a median age of 43.5. The median age when participants started sex work was 17.5, with 60% working 7 days per week and seeing up to 10 clients per night. Eighty percent reported recent unprotected sex and only 30% used some form of contraception. One self-reported sexually transmitted infection at the time of visit and two reported living with HIV. Vaginal secretions showed detectable levels of all biomarkers tested, except MIP3α and MIP1α, which were undetectable in all samples. When stratified by age/menopause status, no significant changes were observed except for Serpin A1 with higher median levels in premenopausal compared to postmenopausal FSW (median 5.79 vs. 5.205 log pg/mL, p = 0.016). Comparison with samples from an existing repository of non-FSW women showed significantly reduced chemokines IL8 (p = 0.045), MIP3α (p ≤ 0.001), and MIP1β (p = 0.015) in the FSW group.
Conclusions
We report characterization of the vaginal secretome in a cohort of FSW in the United States. Understanding of the genital immune microenvironment can inform future research in HIV prevention and therapeutic options in this population.
女性性工作者（FSW）感染 HIV 的比例极高，但美国尚未对可能影响生物风险的阴道免疫微环境特征进行深入研究。此外，在这一人群中收集生物材料的可行方法也尚未得到评估。
{"title":"HIV-Associated Genital Immune Biomarkers in the Female Sex Worker Population: A Pilot Study","authors":"Eleanor Capozzi, Jason Daniels, Hani Mohamed, Fernando Cabezas Mejia, David Sternberg, Jennifer Bouey, Mimi Ghosh","doi":"10.1111/aji.13929","DOIUrl":"10.1111/aji.13929","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Female sex workers (FSW) experience a disproportionately high burden of HIV infection, yet characterization of the vaginal immune microenvironment that may impact biological risk is not well studied among FSW in the United States. Additionally, feasible methodology for collecting biological materials has not been evaluated in this population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled 10 FSW (5 premenopausal, 5 postmenopausal) who participated in a survey and provided vaginal swabs. Biomarkers were assessed by ELISA, and included cytokines, chemokines, and antimicrobial/wound-healing mediators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>One hundred percent of FSW were African American, with a median age of 43.5. The median age when participants started sex work was 17.5, with 60% working 7 days per week and seeing up to 10 clients per night. Eighty percent reported recent unprotected sex and only 30% used some form of contraception. One self-reported sexually transmitted infection at the time of visit and two reported living with HIV. Vaginal secretions showed detectable levels of all biomarkers tested, except MIP3α and MIP1α, which were undetectable in all samples. When stratified by age/menopause status, no significant changes were observed except for Serpin A1 with higher median levels in premenopausal compared to postmenopausal FSW (median 5.79 vs. 5.205 log pg/mL, <i>p</i> = 0.016). Comparison with samples from an existing repository of non-FSW women showed significantly reduced chemokines IL8 (<i>p</i> = 0.045), MIP3α (<i>p</i> ≤ 0.001), and MIP1β (<i>p</i> = 0.015) in the FSW group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We report characterization of the vaginal secretome in a cohort of FSW in the United States. Understanding of the genital immune microenvironment can inform future research in HIV prevention and therapeutic options in this population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255197","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}
Sivan Farladansky-Gershnabel, Michal Silber, Tal Biron-Shental, Michal Kovo, Debora Kidron, Avivit Weisz, Tali Zitman-Gal
Problem
Accelerated placental aging is linked to abnormal fetal growth, preeclampsia (PE), and preterm birth (PTB). NANOG, a transcription factor, is known for its role in cellular reprogramming, self-renewal, and clonogenic growth. Its expression is regulated by Kruppel-like factor 4 (KLF4), which functions as both a transcriptional activator and repressor. This study evaluated the KLF4-NANOG pathway in placental samples from normal pregnancies (NP) as well as those with PE, fetal growth restriction (FGR), and PTB.
Method of Study
Placental samples from NP pregnancies and those with PE, FGR, and PTB were analyzed for NANOG and KLF4 expression using western blotting and immunohistochemistry.
Results
NANOG protein expression was significantly increased in placentas from PE, FGR, and PTB compared to NP (fold changes vs. NP: PE 2.48 ± 0.3, p = 0.002; FGR 1.64 ± 0.16, p = 0.03; PTB 6.03 ± 3.35, p = 0.01). Similarly, KLF4 protein expression was elevated in PE, FGR, and PTB placentas compared to NP (fold changes vs. NP: PE 5.78 ± 0.73, p = 0.001; FGR 2.61 ± 0.43, p = 0.02; PTB 11.42 ± 2.76, p = 0.0006). Immunohistochemistry revealed strong NANOG staining in the syncytiotrophoblast tissue of PE, FGR, and PTB samples, especially in extravillous trophoblasts, compared to NP placentas.
Conclusions
The elevated expression of NANOG and KLF4 in abnormal placental tissues suggests their potential role as markers of enhanced placental aging and dysfunction. These findings underscore the importance of the KLF4-NANOG pathway in the pathology of PE, FGR, and PTB, providing a basis for future research into therapeutic targets for these conditions.
{"title":"Is the Transcription Factor NANOG Involved in Placental Aging?","authors":"Sivan Farladansky-Gershnabel, Michal Silber, Tal Biron-Shental, Michal Kovo, Debora Kidron, Avivit Weisz, Tali Zitman-Gal","doi":"10.1111/aji.13927","DOIUrl":"10.1111/aji.13927","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Accelerated placental aging is linked to abnormal fetal growth, preeclampsia (PE), and preterm birth (PTB). NANOG, a transcription factor, is known for its role in cellular reprogramming, self-renewal, and clonogenic growth. Its expression is regulated by Kruppel-like factor 4 (KLF4), which functions as both a transcriptional activator and repressor. This study evaluated the KLF4-NANOG pathway in placental samples from normal pregnancies (NP) as well as those with PE, fetal growth restriction (FGR), and PTB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Placental samples from NP pregnancies and those with PE, FGR, and PTB were analyzed for NANOG and KLF4 expression using western blotting and immunohistochemistry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NANOG protein expression was significantly increased in placentas from PE, FGR, and PTB compared to NP (fold changes vs. NP: PE 2.48 ± 0.3, <i>p</i> = 0.002; FGR 1.64 ± 0.16, <i>p</i> = 0.03; PTB 6.03 ± 3.35, <i>p</i> = 0.01). Similarly, KLF4 protein expression was elevated in PE, FGR, and PTB placentas compared to NP (fold changes vs. NP: PE 5.78 ± 0.73, <i>p</i> = 0.001; FGR 2.61 ± 0.43, <i>p</i> = 0.02; PTB 11.42 ± 2.76, <i>p</i> = 0.0006). Immunohistochemistry revealed strong NANOG staining in the syncytiotrophoblast tissue of PE, FGR, and PTB samples, especially in extravillous trophoblasts, compared to NP placentas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The elevated expression of NANOG and KLF4 in abnormal placental tissues suggests their potential role as markers of enhanced placental aging and dysfunction. These findings underscore the importance of the KLF4-NANOG pathway in the pathology of PE, FGR, and PTB, providing a basis for future research into therapeutic targets for these conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.13927","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yixiao Wang, Fengyuan Zhang, Li Xu, Xiaohong Ji, Shanshan Wang, Xiao Shen, Haiyan Chen, Shengyuan Jiang, Chengqian Wu, Min Chen, Hong Yu
Objective
Although the association of rheumatoid arthritis (RA) to multiple adverse pregnancy outcomes has been well-studied, the association between serum antibody levels in patients with RA and multiple adverse pregnancy outcomes has not been conclusively demonstrated. Here, we comprehensively assessed the causal impact of RA, serologic antibody-positive RA (pRA), and serologic antibody-negative RA (nRA) on the risk of 14 adverse pregnancy outcomes.
Methods
The causal impact of RA, pRA, and nRA on 14 adverse pregnancy outcomes was comprehensively assessed using two-sample Mendelian randomization (MR). Evidence maps based on the results of these two-sample MR analyses were developed. Data from the UK Biobank and FinnGen databases were utilized for this analysis. The inverse variance weighted (IVW) test was employed as the primary method to estimate causality. “TwoSampleMR” and “MR-PRESSO” packages were used for data analysis in this study.
Results
Using two-sample MR analysis, we found a significant positive causal association between RA and increased risk of cesarean section (p = 0.003), gestational hypertension (p < 0.001), number of spontaneous miscarriages (p = 0.041), preeclampsia (p = 0.008), premature rupture of membranes (p = 0.030), and preterm (p = 0.010). pRA had a significant positive causal association with an increased risk of cesarean section (p = 0.012), gestational hypertension (p < 0.001), preeclampsia (p = 0.002), and preterm (p = 0.007). A significant positive causal association was also established between nRA and gestational hypertension (p = 0.010), the number of spontaneous miscarriages (p = 0.024), and placental abruption (p = 0.027). In addition, we found a causal association between nRA and birth weight (p = 0.007), but not between RA and pRA and birth weight.
Conclusion
The results of this study have important implications for the individualized treatment of RA patients, especially those with positive serum antibody levels.
{"title":"Causal Association of Rheumatoid Arthritis With Adverse Pregnancy Outcomes: Genetic Evidence From Mendelian Randomization","authors":"Yixiao Wang, Fengyuan Zhang, Li Xu, Xiaohong Ji, Shanshan Wang, Xiao Shen, Haiyan Chen, Shengyuan Jiang, Chengqian Wu, Min Chen, Hong Yu","doi":"10.1111/aji.13922","DOIUrl":"https://doi.org/10.1111/aji.13922","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Although the association of rheumatoid arthritis (RA) to multiple adverse pregnancy outcomes has been well-studied, the association between serum antibody levels in patients with RA and multiple adverse pregnancy outcomes has not been conclusively demonstrated. Here, we comprehensively assessed the causal impact of RA, serologic antibody-positive RA (pRA), and serologic antibody-negative RA (nRA) on the risk of 14 adverse pregnancy outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The causal impact of RA, pRA, and nRA on 14 adverse pregnancy outcomes was comprehensively assessed using two-sample Mendelian randomization (MR). Evidence maps based on the results of these two-sample MR analyses were developed. Data from the UK Biobank and FinnGen databases were utilized for this analysis. The inverse variance weighted (IVW) test was employed as the primary method to estimate causality. “TwoSampleMR” and “MR-PRESSO” packages were used for data analysis in this study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Using two-sample MR analysis, we found a significant positive causal association between RA and increased risk of cesarean section (<i>p</i> = 0.003), gestational hypertension (<i>p</i> < 0.001), number of spontaneous miscarriages (<i>p</i> = 0.041), preeclampsia (<i>p</i> = 0.008), premature rupture of membranes (<i>p</i> = 0.030), and preterm (<i>p</i> = 0.010). pRA had a significant positive causal association with an increased risk of cesarean section (<i>p</i> = 0.012), gestational hypertension (<i>p</i> < 0.001), preeclampsia (<i>p</i> = 0.002), and preterm (<i>p</i> = 0.007). A significant positive causal association was also established between nRA and gestational hypertension (<i>p</i> = 0.010), the number of spontaneous miscarriages (<i>p</i> = 0.024), and placental abruption (<i>p</i> = 0.027). In addition, we found a causal association between nRA and birth weight (<i>p</i> = 0.007), but not between RA and pRA and birth weight.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The results of this study have important implications for the individualized treatment of RA patients, especially those with positive serum antibody levels.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230982","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}
G. Aimagambetova, A. Kapasheva, W. Bahia, K. Atageldiyeva, and W. Y. Almawi, “Maternal HLA Class II Alleles and Haplotypes Associated With Altered Risk of Recurrent Pregnancy Loss: A Case-Control Study,” American Journal of Reproductive Immunology, 91 (2024): e13817, https://doi.org/10.1111/aji.13817.
Correction on Section 2.1: Study design and study subjects
Original Text: “This is a retrospective case-control study performed between February 2018 and October 2019 and involving 188 participants (Arabic-speaking Tunisian women)”
Corrected Text: “This is a retrospective case-control study involving 188 participants (Arabic-speaking Tunisian women). Sample collection was done between February 2018 and October 2019, and HLA genotyping was performed between December 2019 and March 2021.”
G. Aimagambetova, A. Kapasheva, W. Bahia, K. Atageldiyeva, and W. Y. Almawi, "Maternal HLA Class II Alleles and Haplotypes Associated With Altered Risk of Recurrent Pregnancy Loss: A Case-Control Study," American Journal of Reproductive Immunology, 91 (2024): e13817, https://doi.org/10.1111/aji.13817.Correction on Section 2.1：研究设计和研究对象原文："这是一项在2018年2月至2019年10月期间进行的回顾性病例对照研究，共有188名参与者（讲阿拉伯语的突尼斯妇女）参与 "更正后的文本："这是一项回顾性病例对照研究，涉及 188 名参与者（讲阿拉伯语的突尼斯女性）。样本采集工作于 2018 年 2 月至 2019 年 10 月期间进行，HLA 基因分型工作于 2019 年 12 月至 2021 年 3 月期间进行"。
{"title":"Correction to “Maternal HLA Class II Alleles and Haplotypes Associated With Altered Risk of Recurrent Pregnancy Loss: A Case-Control Study”","authors":"","doi":"10.1111/aji.13925","DOIUrl":"https://doi.org/10.1111/aji.13925","url":null,"abstract":"<p>G. Aimagambetova, A. Kapasheva, W. Bahia, K. Atageldiyeva, and W. Y. Almawi, “Maternal HLA Class II Alleles and Haplotypes Associated With Altered Risk of Recurrent Pregnancy Loss: A Case-Control Study,” <i>American Journal of Reproductive Immunology</i>, 91 (2024): e13817, https://doi.org/10.1111/aji.13817.</p><p>Correction on Section 2.1: Study design and study subjects</p><p>Original Text: “This is a retrospective case-control study performed between February 2018 and October 2019 and involving 188 participants (Arabic-speaking Tunisian women)”</p><p>Corrected Text: “This is a retrospective case-control study involving 188 participants (Arabic-speaking Tunisian women). Sample collection was done between February 2018 and October 2019, and HLA genotyping was performed between December 2019 and March 2021.”</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.13925","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Endometrial immune cells are essential for maintaining homeostasis and the endometrial receptivity to embryo implantation. Understanding regional variations in endometrial immune cell populations is crucial for comprehending normal endometrial function and the pathophysiology of endometrial disorders. Despite previous studies focusing on the overall immune cell composition and function in the endometrium, regional variations in premenopausal women remain unclear.
Method of Study
Endometrial biopsies were obtained from four regions (anterior, posterior, left lateral, and right lateral) of premenopausal women undergoing hysteroscopy with no abnormalities. A 15-color human endometrial immune cell-focused flow cytometry panel was used for analysis. High-dimensional flow cytometry combined with a clustering algorithm was employed to unravel the complexity of endometrial immune cells. Additionally, multiplex immunofluorescent was performed for further validation.
Results
Our findings revealed no significant variation in the distribution and abundance of immune cells across different regions under normal conditions during the proliferative phase. Each region harbored similar immune cell subtypes, indicating a consistent immune microenvironment. However, when comparing normal regions to areas with focal hemorrhage, significant differences were observed. An increase in CD8+ T cells highlights the impact of localized abnormalities on the immune microenvironment.
Conclusions
Our study demonstrates that the endometrial immune cell landscape is consistent across different anatomical regions during the proliferative phase in premenopausal women. This finding has important implications for understanding normal endometrial function and the pathophysiology of endometrial disorders.
{"title":"Regional Analysis of the Immune Microenvironment in Human Endometrium","authors":"Lingtao Yang, Yiyi Su, Songchen Cai, Huan Ma, Jing Yang, Mingjuan Xu, Yuye Li, Chunyu Huang, Yong Zeng, Qiyuan Li, Mingqian Feng, Hanjie Li, Lianghui Diao","doi":"10.1111/aji.13921","DOIUrl":"10.1111/aji.13921","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Endometrial immune cells are essential for maintaining homeostasis and the endometrial receptivity to embryo implantation. Understanding regional variations in endometrial immune cell populations is crucial for comprehending normal endometrial function and the pathophysiology of endometrial disorders. Despite previous studies focusing on the overall immune cell composition and function in the endometrium, regional variations in premenopausal women remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Endometrial biopsies were obtained from four regions (anterior, posterior, left lateral, and right lateral) of premenopausal women undergoing hysteroscopy with no abnormalities. A 15-color human endometrial immune cell-focused flow cytometry panel was used for analysis. High-dimensional flow cytometry combined with a clustering algorithm was employed to unravel the complexity of endometrial immune cells. Additionally, multiplex immunofluorescent was performed for further validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings revealed no significant variation in the distribution and abundance of immune cells across different regions under normal conditions during the proliferative phase. Each region harbored similar immune cell subtypes, indicating a consistent immune microenvironment. However, when comparing normal regions to areas with focal hemorrhage, significant differences were observed. An increase in CD8<sup>+</sup> T cells highlights the impact of localized abnormalities on the immune microenvironment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study demonstrates that the endometrial immune cell landscape is consistent across different anatomical regions during the proliferative phase in premenopausal women. This finding has important implications for understanding normal endometrial function and the pathophysiology of endometrial disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118821","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}
Serap Topkara Sucu, Berrin Goktuğ Kadioglu, Burak Elmas, Mehmet Caner Ozer, Ulaş Fidan, Mustafa Ozturk, Seyit Temel Ceyhan
Problem
Predicting the impact of systemic inflammation on oocyte and embryonic development in unexplained infertile women using the new immunological indexes.
Method of Study
This retrospective cohort study was conducted using the records of the In Vitro Fertilization Department of Ankara Gülhane Training and Research Hospital. After reviewing the records of patients who had undergone in vitro fertilization (IVF) for unexplained infertility (UI) and excluding all known factors that could cause systemic immune inflammation, the systemic immune response index (SIRI), and pan-immune score were calculated from the pre-treatment hemogram parameters between the embryo arrest (EA) group and the embryo transfer group. It was investigated whether there was a statistical difference between the two groups and whether an SIRI value affecting embryo quality was found. A receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off values for inflammatory markers to predict EA.
Results
The 108 EA group (embryos that were arrested during their development and could not be transferred) and the 140 embryo transfer group showed statistically significant differences in the parameters of systemic inflammatory index (SII), SIRI, pan-immune inflammation value (PIV), and neutrophil/lymphocyte ratio (NLR) (p < 0.05). These inflammatory parameters, which were examined before ovulation induction, also correlated positively with the required total dose of gonadotropin and negatively with the ovarian sensitivity index (OSI). SII, SIRI, PIV, and NLR have specific cut-off values with ROC analysis and determine the effect of the inflammatory status of the environment in which the oocyte develops on EA (p < 0.005).
Conclusion
In women with UI, high levels of systemic immune inflammation have a negative impact on oocyte and embryo development, and treatments to suppress inflammation may improve IVF success.
问题：利用新的免疫学指标预测全身炎症对不明原因不孕妇女卵母细胞和胚胎发育的影响：这项回顾性队列研究使用了安卡拉居尔哈尼培训与研究医院体外受精科的记录。在审查了接受体外受精（IVF）治疗的不明原因不孕症（UI）患者的病历并排除所有可能导致全身免疫炎症的已知因素后，根据胚胎停育（EA）组和胚胎移植组治疗前的血液图参数计算了全身免疫反应指数（SIRI）和泛免疫评分。研究了两组之间是否存在统计学差异，以及是否发现了影响胚胎质量的 SIRI 值。为了确定预测 EA 的最佳炎症标志物临界值，进行了接收者操作特征（ROC）曲线分析：结果：108 例 EA 组（胚胎在发育过程中停滞，无法移植）和 140 例胚胎移植组在全身炎症指数 (SII)、SIRI、泛免疫炎症值 (PIV) 和中性粒细胞/淋巴细胞比值 (NLR) 等参数上存在显著统计学差异（P < 0.05）。在诱导排卵前检查的这些炎症参数还与所需的促性腺激素总剂量呈正相关，与卵巢敏感性指数（OSI）呈负相关。通过 ROC 分析，SII、SIRI、PIV 和 NLR 具有特定的临界值，可确定卵母细胞发育环境的炎症状态对 EA 的影响（P < 0.005）：在患有子宫内膜异位症的妇女中，高水平的全身免疫炎症会对卵母细胞和胚胎的发育产生负面影响，抑制炎症的治疗可提高试管婴儿的成功率。
{"title":"New Immunological Indexes for the Effect of Systemic Inflammation on Oocyte and Embryo Development in Women With Unexplained Infertility: Systemic Immune Response Index and Pan-Immune-Inflammation Value","authors":"Serap Topkara Sucu, Berrin Goktuğ Kadioglu, Burak Elmas, Mehmet Caner Ozer, Ulaş Fidan, Mustafa Ozturk, Seyit Temel Ceyhan","doi":"10.1111/aji.13923","DOIUrl":"10.1111/aji.13923","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Predicting the impact of systemic inflammation on oocyte and embryonic development in unexplained infertile women using the new immunological indexes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>This retrospective cohort study was conducted using the records of the In Vitro Fertilization Department of Ankara Gülhane Training and Research Hospital. After reviewing the records of patients who had undergone in vitro fertilization (IVF) for unexplained infertility (UI) and excluding all known factors that could cause systemic immune inflammation, the systemic immune response index (SIRI), and pan-immune score were calculated from the pre-treatment hemogram parameters between the embryo arrest (EA) group and the embryo transfer group. It was investigated whether there was a statistical difference between the two groups and whether an SIRI value affecting embryo quality was found. A receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off values for inflammatory markers to predict EA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The 108 EA group (embryos that were arrested during their development and could not be transferred) and the 140 embryo transfer group showed statistically significant differences in the parameters of systemic inflammatory index (SII), SIRI, pan-immune inflammation value (PIV), and neutrophil/lymphocyte ratio (NLR) (<i>p</i> < 0.05). These inflammatory parameters, which were examined before ovulation induction, also correlated positively with the required total dose of gonadotropin and negatively with the ovarian sensitivity index (OSI). SII, SIRI, PIV, and NLR have specific cut-off values with ROC analysis and determine the effect of the inflammatory status of the environment in which the oocyte develops on EA (<i>p</i> < 0.005).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In women with UI, high levels of systemic immune inflammation have a negative impact on oocyte and embryo development, and treatments to suppress inflammation may improve IVF success.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103573","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}
Jing Gao, Nanyan Jiang, Qi Chen, Min Zhao, Yunhui Tang
Problem
Cesarean scar pregnancy (CSP) is characterized by a gestational sac fully or partially implanted in the scar from a previous cesarean section. Systemic immune-inflammation indices (SIIs) have recently been discussed as additional diagnostic markers in placenta accreta and preeclampsia. CSP shares a similar pathogenesis with these diseases, suggesting that assessing the SIIs and neutrophil-to-lymphocyte ratio (NLR) could enhance additional predictability in diagnosing CSP.
Method of Study
In this study, we analyzed the complete blood counts between 264 women who were confirmed with CSP by ultrasound and 295 women who underwent elective termination.
Results
The mean counts of total white cells and neutrophils were significantly higher, whereas the counts of monocytes, lymphocytes, and platelets were significantly lower in the CSP group compared to the control group (p < 0.001). Additionally, the SII, systemic inflammation response index (SIRI), or NLR was significantly higher in the CSP group compared to the control group (p < 0.0001). Given the limited effect of SII and SIRI on the increased risk of developing CSP, the optimal cut-off value for NLR in predicting CSP was 2.87 (area under the curve [AUC] 0.656, 68% sensitivity). The optimal cut-off value for NLR in predicting type 2 CSP was 2.91 (AUC 0.690, 71% sensitivity).
Conclusions
Although ultrasound or magnetic resonance imaging images are a gold standard for visualizing the gestational sac's location in the diagnosis of CSP, assessing peripheral blood tests is cost-effective, and NLR may provide additional diagnosis value for CSP.
{"title":"Systemic Immune-Inflammation Indices Could Be Additional Predictive Markers for Cesarean Scar Pregnancy","authors":"Jing Gao, Nanyan Jiang, Qi Chen, Min Zhao, Yunhui Tang","doi":"10.1111/aji.13924","DOIUrl":"10.1111/aji.13924","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Cesarean scar pregnancy (CSP) is characterized by a gestational sac fully or partially implanted in the scar from a previous cesarean section. Systemic immune-inflammation indices (SIIs) have recently been discussed as additional diagnostic markers in placenta accreta and preeclampsia. CSP shares a similar pathogenesis with these diseases, suggesting that assessing the SIIs and neutrophil-to-lymphocyte ratio (NLR) could enhance additional predictability in diagnosing CSP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>In this study, we analyzed the complete blood counts between 264 women who were confirmed with CSP by ultrasound and 295 women who underwent elective termination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean counts of total white cells and neutrophils were significantly higher, whereas the counts of monocytes, lymphocytes, and platelets were significantly lower in the CSP group compared to the control group (<i>p</i> < 0.001). Additionally, the SII, systemic inflammation response index (SIRI), or NLR was significantly higher in the CSP group compared to the control group (<i>p</i> < 0.0001). Given the limited effect of SII and SIRI on the increased risk of developing CSP, the optimal cut-off value for NLR in predicting CSP was 2.87 (area under the curve [AUC] 0.656, 68% sensitivity). The optimal cut-off value for NLR in predicting type 2 CSP was 2.91 (AUC 0.690, 71% sensitivity).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although ultrasound or magnetic resonance imaging images are a gold standard for visualizing the gestational sac's location in the diagnosis of CSP, assessing peripheral blood tests is cost-effective, and NLR may provide additional diagnosis value for CSP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103574","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}
Federica Giangrazi, Dafne Buffa, Andrew T. Lloyd, Anthony K. Redmond, Louise E. Glover, Cliona O'Farrelly
Problem
The interleukin-17 (IL-17) family includes pro-inflammatory cytokines IL-17A-F with important roles in mucosal defence, barrier integrity and tissue regeneration. IL-17A can be dysregulated in fertility complications, including pre-eclampsia, endometriosis and miscarriage. Because mammalian subclasses (eutherian, metatherian, and prototherian) have different related reproductive strategies, IL-17 genes and proteins were investigated in the three mammalian classes to explore their involvement in female fertility.
Method of Study
Gene and protein sequences for IL-17s are found in eutherian, metatherian and prototherian mammals. Through synteny and multiple sequence protein alignment, the relationships among mammalian IL-17s were inferred. Publicly available datasets of early pregnancy stages and female fertility in therian mammals were collected and analysed to retrieve information on IL-17 expression.
Results
Synteny mapping and phylogenetic analyses allowed the classification of mammalian IL-17 family orthologs of human IL-17. Despite differences in their primary amino acid sequence, metatherian and prototherian IL-17s share the same tertiary structure as human IL-17s, suggesting similar functions. The analysis of available datasets for female fertility in therian mammals shows up-regulation of IL-17A and IL-17D during placentation. IL-17B and IL-17D are also found to be over-expressed in human fertility complication datasets, such as endometriosis or recurrent implantation failure.
Conclusions
The conservation of the IL-17 gene and protein across mammals suggests similar functions in all the analysed species. Despite significant differences, the upregulation of IL-17 expression is associated with the establishment of pregnancy in eutherian and metatherian mammals. The dysregulation of IL-17s in human reproductive disorders suggests them as a potential therapeutic target.
{"title":"Evolutionary Analysis of the Mammalian IL-17 Cytokine Family Suggests Conserved Roles in Female Fertility","authors":"Federica Giangrazi, Dafne Buffa, Andrew T. Lloyd, Anthony K. Redmond, Louise E. Glover, Cliona O'Farrelly","doi":"10.1111/aji.13907","DOIUrl":"10.1111/aji.13907","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>The interleukin-17 (IL-17) family includes pro-inflammatory cytokines IL-17A-F with important roles in mucosal defence, barrier integrity and tissue regeneration. IL-17A can be dysregulated in fertility complications, including pre-eclampsia, endometriosis and miscarriage. Because mammalian subclasses (eutherian, metatherian, and prototherian) have different related reproductive strategies, IL-17 genes and proteins were investigated in the three mammalian classes to explore their involvement in female fertility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Gene and protein sequences for IL-17s are found in eutherian, metatherian and prototherian mammals. Through synteny and multiple sequence protein alignment, the relationships among mammalian IL-17s were inferred. Publicly available datasets of early pregnancy stages and female fertility in therian mammals were collected and analysed to retrieve information on IL-17 expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Synteny mapping and phylogenetic analyses allowed the classification of mammalian IL-17 family orthologs of human IL-17. Despite differences in their primary amino acid sequence, metatherian and prototherian IL-17s share the same tertiary structure as human IL-17s, suggesting similar functions. The analysis of available datasets for female fertility in therian mammals shows up-regulation of IL-17A and IL-17D during placentation. IL-17B and IL-17D are also found to be over-expressed in human fertility complication datasets, such as endometriosis or recurrent implantation failure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The conservation of the IL-17 gene and protein across mammals suggests similar functions in all the analysed species. Despite significant differences, the upregulation of IL-17 expression is associated with the establishment of pregnancy in eutherian and metatherian mammals. The dysregulation of IL-17s in human reproductive disorders suggests them as a potential therapeutic target.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.13907","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Federica Giangrazi, Dafne Buffa, Andrew T. Lloyd, Anthony K. Redmond, Louise E. Glover, Cliona O'Farrelly
The cover image is based on the Article Evolutionary Analysis of the Mammalian IL-17 Cytokine Family Suggests Conserved Roles in Female Fertility by Cliona O'Farrelly et al., https://doi.org/10.1111/aji.13907.
封面图片基于 Cliona O'Farrelly 等人撰写的文章《哺乳动物 IL-17 细胞因子家族的进化分析表明其在女性生育中的作用得到保留》（Evolutionary Analysis of the Mammalian IL-17 Cytokine Family Suggests Conserved Roles in Female Fertility），https://doi.org/10.1111/aji.13907。
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