Morteza Abdi, Manouchehr Fadaee, Amirreza jourabchi, Hadi Karimzadeh, Tohid Kazemi
An important drawback of anticancer chemotherapy is the harm it causes to healthy cells. Cyclophosphamide (CP) is a widely used chemotherapeutic alkylating agent that is regularly used in cancer treatment. However, it can cause severe side effects, including genotoxicity, due to its ability to damage DNA. This toxicity is thought to be associated with oxidative stress induced by an excessive amount of reactive oxygen species (ROS). Therefore, there is a specific focus on the potential effects of anticancer treatments on fertility. Due to the increasing life expectancy of cancer patients, those desiring parenthood may face the negative impacts of therapies. Utilizing substances with antioxidant and cytoprotective characteristics to protect the reproductive system from harmful consequences during chemotherapy would be highly beneficial. This review introduces the physiological and pathological roles of ROS in the reproductive systems of both males and females, then we address the adverse effects of CP administration on infertility and discuss how antioxidants can reverse these effects.
{"title":"Cyclophosphamide-Induced Infertility and the Impact of Antioxidants","authors":"Morteza Abdi, Manouchehr Fadaee, Amirreza jourabchi, Hadi Karimzadeh, Tohid Kazemi","doi":"10.1111/aji.70014","DOIUrl":"https://doi.org/10.1111/aji.70014","url":null,"abstract":"<div>\u0000 \u0000 <p>An important drawback of anticancer chemotherapy is the harm it causes to healthy cells. Cyclophosphamide (CP) is a widely used chemotherapeutic alkylating agent that is regularly used in cancer treatment. However, it can cause severe side effects, including genotoxicity, due to its ability to damage DNA. This toxicity is thought to be associated with oxidative stress induced by an excessive amount of reactive oxygen species (ROS). Therefore, there is a specific focus on the potential effects of anticancer treatments on fertility. Due to the increasing life expectancy of cancer patients, those desiring parenthood may face the negative impacts of therapies. Utilizing substances with antioxidant and cytoprotective characteristics to protect the reproductive system from harmful consequences during chemotherapy would be highly beneficial. This review introduces the physiological and pathological roles of ROS in the reproductive systems of both males and females, then we address the adverse effects of CP administration on infertility and discuss how antioxidants can reverse these effects.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764160","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}
Maeva Wendremaire, Tarik Hadi, Tatiana E. Lopez, Julien Guy, Fabrice Neiers, Carmen Garrido, Emmanuel Simon, Zohra Jaffal, Virginie Bernigal, Marc Bardou, Frédéric Lirussi
Problem
Preterm birth (PTB) remains the leading cause of neonatal morbidity and mortality. Identifying women at high risk of spontaneous preterm labor (PTL) is challenging due to limited efficient diagnostic markers. Since human parturition involves inflammatory immune processes, we hypothesized that phenotyping of maternal peripheral lymphocytes might predict PTL. Therefore, we aimed to explore the relationship between maternal lymphocyte subpopulations and labor onset characterized by delivery within 7 days of admission in women hospitalized for PTL between 24 and 34 weeks of gestation.
Methods of Study
Lymphocyte subpopulations were obtained from peripheral blood samples and characterized by flow cytometry: activated and regulatory T cells, natural killer and B cells, and TH1/TH2/TH17 lymphocytes. Data analysis was conducted retrospectively based on the delivery within 7 days of admission.
Results
Among 167 women admitted for PTL, less than 10% delivered within 7 days post-admission. HLA-DR expression was significantly increased on CD4+CD8−, CD4−CD8+, and CD4+CD8+ lymphocytes in women who delivered within 7 days. Subset levels below 5% of CD4+CD8−HLA-DR+ lymphocytes and 20% of CD4+CD8+HLA-DR+ lymphocytes were associated with no probability of delivering within 7 days.
Conclusion
Our study suggests that combining these two consecutive markers allowed us to identify 57% of women hospitalized for PTL with no probability of delivering within 7 days while retaining patients who delivered within 7 days. If prospectively validated, these markers may be able to identify patients at high risk of PTB and avoid a significant number of unnecessary admissions and healthcare costs.
{"title":"Immunophenotyping and Activation Status of Maternal Lymphocytes to Predict Spontaneous Preterm Birth in Women With Threatened Preterm Labor: A Prospective Observational Study","authors":"Maeva Wendremaire, Tarik Hadi, Tatiana E. Lopez, Julien Guy, Fabrice Neiers, Carmen Garrido, Emmanuel Simon, Zohra Jaffal, Virginie Bernigal, Marc Bardou, Frédéric Lirussi","doi":"10.1111/aji.70015","DOIUrl":"https://doi.org/10.1111/aji.70015","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Preterm birth (PTB) remains the leading cause of neonatal morbidity and mortality. Identifying women at high risk of spontaneous preterm labor (PTL) is challenging due to limited efficient diagnostic markers. Since human parturition involves inflammatory immune processes, we hypothesized that phenotyping of maternal peripheral lymphocytes might predict PTL. Therefore, we aimed to explore the relationship between maternal lymphocyte subpopulations and labor onset characterized by delivery within 7 days of admission in women hospitalized for PTL between 24 and 34 weeks of gestation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods of Study</h3>\u0000 \u0000 <p>Lymphocyte subpopulations were obtained from peripheral blood samples and characterized by flow cytometry: activated and regulatory T cells, natural killer and B cells, and T<sub>H</sub>1/T<sub>H</sub>2/T<sub>H</sub>17 lymphocytes. Data analysis was conducted retrospectively based on the delivery within 7 days of admission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 167 women admitted for PTL, less than 10% delivered within 7 days post-admission. HLA-DR expression was significantly increased on CD4<sup>+</sup>CD8<sup>−</sup>, CD4<sup>−</sup>CD8<sup>+</sup>, and CD4<sup>+</sup>CD8<sup>+</sup> lymphocytes in women who delivered within 7 days. Subset levels below 5% of CD4<sup>+</sup>CD8<sup>−</sup>HLA-DR<sup>+</sup> lymphocytes and 20% of CD4<sup>+</sup>CD8<sup>+</sup>HLA-DR<sup>+</sup> lymphocytes were associated with no probability of delivering within 7 days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study suggests that combining these two consecutive markers allowed us to identify 57% of women hospitalized for PTL with no probability of delivering within 7 days while retaining patients who delivered within 7 days. If prospectively validated, these markers may be able to identify patients at high risk of PTB and avoid a significant number of unnecessary admissions and healthcare costs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ANSM number: 2010-A00516-33; ClinicalTrials.gov identifier: NCT01340222</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764117","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}
Fibroids are the most common benign tumors of the female reproductive system. Most patients with fibroids are asymptomatic, but the presence of fibroids can still cause some abnormal clinical symptoms, such as increased menstrual volume, abnormal uterine bleeding, pelvic pain, urinary tract and gastrointestinal tract compression symptoms, etc. The impact of fibroids on pregnancy is worth discussing. At present, it is believed that submucosal myoma and intramural myoma affecting uterine cavity shape affect the pregnancy outcome of patients, while the impact of type III intramural myoma on pregnancy is still controversial. A number of studies have found that in addition to direct contact with the endometrial compression, uterine myoma also affects the endometrial flexibility through other ways. In this review, we summarized the effects of fibroids on endometrial receptivity and discussed in depth the mechanisms of such effects, including secretion of cytokines, changes in endometrial blood flow and angiogenesis, effects on endometrial peristalsis and mechanical stress conduction, changes in uterine microecological environment, and abnormal signal transduction pathways. Understanding the mechanism of endometrial receptivity affected by fibroids is significant for exploring the treatment of fibroids, improving the pregnancy outcome of patients with fibroids and increasing the clinical pregnancy rate.
{"title":"Mechanism of Endometrial Receptivity Affected by Fibroids","authors":"Ping Sun, Chunyan Zhang, Weisha Wang, Huagang Ma","doi":"10.1111/aji.70022","DOIUrl":"https://doi.org/10.1111/aji.70022","url":null,"abstract":"<p>Fibroids are the most common benign tumors of the female reproductive system. Most patients with fibroids are asymptomatic, but the presence of fibroids can still cause some abnormal clinical symptoms, such as increased menstrual volume, abnormal uterine bleeding, pelvic pain, urinary tract and gastrointestinal tract compression symptoms, etc. The impact of fibroids on pregnancy is worth discussing. At present, it is believed that submucosal myoma and intramural myoma affecting uterine cavity shape affect the pregnancy outcome of patients, while the impact of type III intramural myoma on pregnancy is still controversial. A number of studies have found that in addition to direct contact with the endometrial compression, uterine myoma also affects the endometrial flexibility through other ways. In this review, we summarized the effects of fibroids on endometrial receptivity and discussed in depth the mechanisms of such effects, including secretion of cytokines, changes in endometrial blood flow and angiogenesis, effects on endometrial peristalsis and mechanical stress conduction, changes in uterine microecological environment, and abnormal signal transduction pathways. Understanding the mechanism of endometrial receptivity affected by fibroids is significant for exploring the treatment of fibroids, improving the pregnancy outcome of patients with fibroids and increasing the clinical pregnancy rate.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764118","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}
This study aims to introduce the Bayesian kernel machine regression (BKMR) model to explore the single and joint associations between exposure to blood cell-based inflammatory in early pregnant women and gestational diabetes mellitus (GDM).
Method of Study
The study included 536 singleton pregnant women from the Zunyi Birth Cohort. Logistic regression, restricted cubic spline regression, and BKMR were used to investigate single, nonlinear, and combined associations.
Results
In this study, the adjusted odds ratio (OR) of white blood cell (WBC), neutrophil (NEUT), monocyte (MONO), platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII) were 2.20 (95% confidence interval [CI]: 1.43–3.37), 2.27 (95% CI: 1.48–3.48), 1.67 (95% CI: 1.09–2.57), 1.66 (95% CI: 1.07–2.58), 1.65 (95% CI: 1.08–2.54), and 1.89 (95% CI: 1.23–2.91), respectively. Nonlinear associations of WBC (cutoff level: 7.91 × 109/L) and NEUT (cutoff level: 5.52 × 109/L) with GDM were also observed. Furthermore, BKMR analysis showed that the risk of GDM was linked with increased levels of blood cell-based inflammatory indicators.
Conclusion
In early pregnancy, multiple blood cell-based inflammatory indicators are significantly positively correlated with the risk of GDM. Specifically, WBC and NEUT counts exhibit the most prominent association with GDM risk. Therefore, more attention should be paid to the inflammation levels of early pregnant women.
{"title":"Single and Joint Associations Between Blood Cell-Based Inflammatory Indicator in Early Pregnancy and Risk of Gestational Diabetes Mellitus (GDM): A Prospective Cohort Study","authors":"Yanling Xiao, Haonan Zhang, Songlin An, Rui Yu, Jing Yang, Xingting Zheng, Nian Wu, Lin Tao, Dengqing Liao, Mingyu Deng, Zhongmei Hu, Yijun Liu, Qing Chen, Yuanzhong Zhou","doi":"10.1111/aji.70021","DOIUrl":"https://doi.org/10.1111/aji.70021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>This study aims to introduce the Bayesian kernel machine regression (BKMR) model to explore the single and joint associations between exposure to blood cell-based inflammatory in early pregnant women and gestational diabetes mellitus (GDM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>The study included 536 singleton pregnant women from the Zunyi Birth Cohort. Logistic regression, restricted cubic spline regression, and BKMR were used to investigate single, nonlinear, and combined associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this study, the adjusted odds ratio (OR) of white blood cell (WBC), neutrophil (NEUT), monocyte (MONO), platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII) were 2.20 (95% confidence interval [CI]: 1.43–3.37), 2.27 (95% CI: 1.48–3.48), 1.67 (95% CI: 1.09–2.57), 1.66 (95% CI: 1.07–2.58), 1.65 (95% CI: 1.08–2.54), and 1.89 (95% CI: 1.23–2.91), respectively. Nonlinear associations of WBC (cutoff level: 7.91 × 10<sup>9</sup>/L) and NEUT (cutoff level: 5.52 × 10<sup>9</sup>/L) with GDM were also observed. Furthermore, BKMR analysis showed that the risk of GDM was linked with increased levels of blood cell-based inflammatory indicators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In early pregnancy, multiple blood cell-based inflammatory indicators are significantly positively correlated with the risk of GDM. Specifically, WBC and NEUT counts exhibit the most prominent association with GDM risk. Therefore, more attention should be paid to the inflammation levels of early pregnant women.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764116","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}
Jin-Sol Park, Ah-Yun Song, Ju-Young Bae, Jae Won Han, Tae Hyun Kim, Chul-Jung Kim, Sung Ki Lee
<div> <section> <h3> Problem</h3> <p>The imbalance in the Th17/Regulatory T (Treg) cell ratio is associated with recurrent pregnancy loss (RPL). This study aimed to determine a cut-off for the Th17/Treg cell ratio to predict pregnancy outcomes in RPL and evaluate the effectiveness of intravenous immunoglobulin (IVIG) based on this cut-off value.</p> </section> <section> <h3> Method of Study</h3> <p>This retrospective cohort study included 49 idiopathic RPL and 75 controls. The subgroups of IL-17<sup>+</sup> T cell to Foxp3<sup>+</sup> T cell ratios in peripheral blood were measured using flow cytometry. The cut-off values of Th17/Treg cell ratios were determined by the ROC curve to distinguish between RPL and controls. The IVIG treatment effectiveness in pregnancy outcome was compared between high- and low-ratio groups. Pearson correlation assessed the Th17/Treg cell ratio's relationship with NK cell cytotoxicity (NKC), NK cell percentage, and Th1/Th2 cell ratio.</p> </section> <section> <h3> Results</h3> <p>Using the ROC curve, we identified six Th17/Treg cell ratio markers with diagnostic value, and the following two, CD3<sup>+</sup>IL-17<sup>+</sup> T cell/CD3<sup>+</sup>Foxp3<sup>high</sup> T cell ratio (sensitivity at 97%) and CD4<sup>+</sup>IL-17<sup>+</sup> T cell/CD3<sup>+</sup>Foxp3<sup>high</sup> T cell ratio (specificity at 93.61%), showed the highest statistical significance in diagnosing idiopathic RPL. Among the six diagnostic markers, in terms of predicting pregnancy outcomes with IVIG treatment, CD3<sup>+</sup>IL-17<sup>+</sup> T cell/CD4<sup>+</sup>Foxp3<sup>+</sup> T cell ratio was the most valuable prognostic marker. In RPL women with high CD3<sup>+</sup>IL-17<sup>+</sup> T cell/CD4<sup>+</sup>Foxp3<sup>+</sup> T cell ratio (≥ 1.096), the live birth rate (LBR) was improved with IVIG treatment. (IVIG treatment, 78.57% vs. no IVIG, 28.57%, <i>p</i> = 0.026). On the other hand, RPL women with low CD3<sup>+</sup>IL-17<sup>+</sup> T cell/CD4<sup>+</sup>Foxp3<sup>+</sup> T cell ratio did not demonstrate the effectiveness of IVIG (LBRs with IVIG treatment, 50.00% vs. no IVIG, 84.62%, <i>p</i> = 0.219). In a correlation study, the CD3<sup>+</sup>IL-17<sup>+</sup> T cell/CD4<sup>+</sup>Foxp3<sup>+</sup> T cell ratio was an independent prognostic marker, showing no correlation with NKC, NK cell percentage, and Th1/Th2 cell ratio.</p> </section> <section> <h3> Conclusion</h3> <p>The CD3<sup>+</sup>IL-17<sup>+</sup> T/CD4<sup>+</sup>Foxp3<sup>+</sup> T cell ratio may serve as a valuable marker for understanding the pathogenesis of RPL, predicting pregnancy outcomes, and selecting candidates for immunotherapy. Our study demo
问题 Th17/调节性 T（Treg）细胞比率失衡与复发性妊娠失败（RPL）有关。本研究旨在确定Th17/Treg细胞比率的临界值，以预测RPL的妊娠结局，并根据该临界值评估静脉注射免疫球蛋白（IVIG）的效果。 研究方法 这项回顾性队列研究包括 49 例特发性 RPL 和 75 例对照组。使用流式细胞术测量了外周血中 IL-17+ T 细胞与 Foxp3+ T 细胞比率的亚组。通过 ROC 曲线确定 Th17/Treg 细胞比率的临界值，以区分 RPL 和对照组。比较了高比率组和低比率组的 IVIG 治疗对妊娠结局的影响。皮尔逊相关性评估了Th17/Treg细胞比率与NK细胞细胞毒性（NKC）、NK细胞百分比和Th1/Th2细胞比率的关系。 结果 利用 ROC 曲线，我们确定了 6 个具有诊断价值的 Th17/Treg 细胞比值标志物，其中 CD3+IL-17+ T 细胞/CD3+Foxp3高 T 细胞比值（敏感性为 97%）和 CD4+IL-17+ T 细胞/CD3+Foxp3高 T 细胞比值（特异性为 93.61%）在诊断特发性 RPL 中显示出最高的统计学意义。在六种诊断标志物中，CD3+IL-17+ T 细胞/CD4+Foxp3+ T 细胞比值是预测 IVIG 治疗妊娠结局的最有价值的预后标志物。在 CD3+IL-17+ T 细胞/CD4+Foxp3+ T 细胞比值较高（≥ 1.096）的 RPL 妇女中，IVIG 治疗可提高活产率（LBR）。(IVIG治疗，78.57%；无IVIG治疗，28.57%，P = 0.026）。另一方面，CD3+IL-17+ T 细胞/CD4+Foxp3+ T 细胞比值较低的 RPL 妇女并没有显示出 IVIG 的有效性（接受 IVIG 治疗的活产率为 50.00%，不接受 IVIG 治疗的活产率为 84.62%，P = 0.219）。在一项相关性研究中，CD3+IL-17+ T 细胞/CD4+Foxp3+ T 细胞比值是一个独立的预后指标，与 NKC、NK 细胞百分比和 Th1/Th2 细胞比值没有相关性。 结论 CD3+IL-17+ T/CD4+Foxp3+ T 细胞比值可作为了解 RPL 发病机制、预测妊娠结局和选择免疫疗法候选者的重要标志物。我们的研究表明，IVIG 治疗可显著改善 CD3+IL-17+ T/CD4+Foxp3+ T 比率高的妇女的 LBR，为这一具有挑战性的病症提供了一种有前景的治疗方法。
{"title":"IL-17 Producing T to Foxp3+CD4+ Regulatory T Cell Ratio as a Diagnostic and Prognostic Marker in Women With Recurrent Pregnancy Loss and Its Implications for Intravenous Immunoglobulin Therapy","authors":"Jin-Sol Park, Ah-Yun Song, Ju-Young Bae, Jae Won Han, Tae Hyun Kim, Chul-Jung Kim, Sung Ki Lee","doi":"10.1111/aji.70020","DOIUrl":"https://doi.org/10.1111/aji.70020","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>The imbalance in the Th17/Regulatory T (Treg) cell ratio is associated with recurrent pregnancy loss (RPL). This study aimed to determine a cut-off for the Th17/Treg cell ratio to predict pregnancy outcomes in RPL and evaluate the effectiveness of intravenous immunoglobulin (IVIG) based on this cut-off value.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>This retrospective cohort study included 49 idiopathic RPL and 75 controls. The subgroups of IL-17<sup>+</sup> T cell to Foxp3<sup>+</sup> T cell ratios in peripheral blood were measured using flow cytometry. The cut-off values of Th17/Treg cell ratios were determined by the ROC curve to distinguish between RPL and controls. The IVIG treatment effectiveness in pregnancy outcome was compared between high- and low-ratio groups. Pearson correlation assessed the Th17/Treg cell ratio's relationship with NK cell cytotoxicity (NKC), NK cell percentage, and Th1/Th2 cell ratio.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Using the ROC curve, we identified six Th17/Treg cell ratio markers with diagnostic value, and the following two, CD3<sup>+</sup>IL-17<sup>+</sup> T cell/CD3<sup>+</sup>Foxp3<sup>high</sup> T cell ratio (sensitivity at 97%) and CD4<sup>+</sup>IL-17<sup>+</sup> T cell/CD3<sup>+</sup>Foxp3<sup>high</sup> T cell ratio (specificity at 93.61%), showed the highest statistical significance in diagnosing idiopathic RPL. Among the six diagnostic markers, in terms of predicting pregnancy outcomes with IVIG treatment, CD3<sup>+</sup>IL-17<sup>+</sup> T cell/CD4<sup>+</sup>Foxp3<sup>+</sup> T cell ratio was the most valuable prognostic marker. In RPL women with high CD3<sup>+</sup>IL-17<sup>+</sup> T cell/CD4<sup>+</sup>Foxp3<sup>+</sup> T cell ratio (≥ 1.096), the live birth rate (LBR) was improved with IVIG treatment. (IVIG treatment, 78.57% vs. no IVIG, 28.57%, <i>p</i> = 0.026). On the other hand, RPL women with low CD3<sup>+</sup>IL-17<sup>+</sup> T cell/CD4<sup>+</sup>Foxp3<sup>+</sup> T cell ratio did not demonstrate the effectiveness of IVIG (LBRs with IVIG treatment, 50.00% vs. no IVIG, 84.62%, <i>p</i> = 0.219). In a correlation study, the CD3<sup>+</sup>IL-17<sup>+</sup> T cell/CD4<sup>+</sup>Foxp3<sup>+</sup> T cell ratio was an independent prognostic marker, showing no correlation with NKC, NK cell percentage, and Th1/Th2 cell ratio.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The CD3<sup>+</sup>IL-17<sup>+</sup> T/CD4<sup>+</sup>Foxp3<sup>+</sup> T cell ratio may serve as a valuable marker for understanding the pathogenesis of RPL, predicting pregnancy outcomes, and selecting candidates for immunotherapy. Our study demo","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708054","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}
Gulcan Okutucu, Atakan Tanacan, Sengul Kara, Osman Onur Ozkavak, Aysegul Atalay, Ozgur Kara, Dilek Sahin
Aims
To investigate whether systemic inflammatory indices and the last trimester APRI score change in PGDM and to evaluate the relationship between these alterations and perinatal outcomes.
Methods
A total of 240 pregnant women, 120 of whom were pregestational diabetic (40 with T1DM and 80 with T2DM), were analyzed. In each trimester, WBC, NEU, LNF, PLT, NLR, dNLR, PLR, PNR, and SII values, and in the last trimester MON, PMR, SIRI, AST values, and APRI score were recorded and compared between PGDM and control cohorts.
Results
The first trimester WBC, NEU, and LNF values were higher and the PNR values were lower, the second trimester LNF value was higher and the NLR was lower, the third trimester APRI score was higher in the PGDM group. In diabetic pregnant women, the optimal cut-off value of NEU for predicting LBW in the first trimester was 6.965 × 10⁹/L (62.5% sensitivity and 61.6% specificity), while the optimal cut-off value of the last trimester APRI score for predicting preterm delivery was 0.072 (61.9% sensitivity and 61.6% specificity). In predicting NICU, the optimal cut-off value for second trimester NLR was found to be 3.973 (70% sensitivity and 70% specificity) in the T1DM group, while the optimal cut-off values for first and second trimester LNF were 2.395 × 10⁹/L (75% sensitivity and 71.1% specificity) and 2.23 × 10⁹/L (75% sensitivity and 68.4% specificity) in the T2DM group, respectively.
Conclusions
In routine clinical practice, the first trimester NLR and last trimester APRI score may be used as additional tools for predicting perinatal outcomes in pregnancies affected by PGDM.
{"title":"Association of Systemic Inflammatory Indices and Last Trimester APRI Score With Perinatal Outcomes in Pregnant Women With Pregestational Diabetes–A Prospective Observational Study","authors":"Gulcan Okutucu, Atakan Tanacan, Sengul Kara, Osman Onur Ozkavak, Aysegul Atalay, Ozgur Kara, Dilek Sahin","doi":"10.1111/aji.70018","DOIUrl":"10.1111/aji.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate whether systemic inflammatory indices and the last trimester APRI score change in PGDM and to evaluate the relationship between these alterations and perinatal outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 240 pregnant women, 120 of whom were pregestational diabetic (40 with T1DM and 80 with T2DM), were analyzed. In each trimester, WBC, NEU, LNF, PLT, NLR, dNLR, PLR, PNR, and SII values, and in the last trimester MON, PMR, SIRI, AST values, and APRI score were recorded and compared between PGDM and control cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The first trimester WBC, NEU, and LNF values were higher and the PNR values were lower, the second trimester LNF value was higher and the NLR was lower, the third trimester APRI score was higher in the PGDM group. In diabetic pregnant women, the optimal cut-off value of NEU for predicting LBW in the first trimester was 6.965 × 10⁹/L (62.5% sensitivity and 61.6% specificity), while the optimal cut-off value of the last trimester APRI score for predicting preterm delivery was 0.072 (61.9% sensitivity and 61.6% specificity). In predicting NICU, the optimal cut-off value for second trimester NLR was found to be 3.973 (70% sensitivity and 70% specificity) in the T1DM group, while the optimal cut-off values for first and second trimester LNF were 2.395 × 10⁹/L (75% sensitivity and 71.1% specificity) and 2.23 × 10⁹/L (75% sensitivity and 68.4% specificity) in the T2DM group, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In routine clinical practice, the first trimester NLR and last trimester APRI score may be used as additional tools for predicting perinatal outcomes in pregnancies affected by PGDM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685682","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}
Intrauterine infection is one of the most jeopardizing conditions associated with adverse outcomes, including preterm birth; however, multiple tolerance mechanisms operate at the maternal–fetal interface to avoid the rejection of the fetus. Among the factors that maintain the uterus as an immunoprivileged site, Galectin-1 (Gal-1), an immunomodulatory glycan-binding protein secreted by the maternal-fetal unit, is pivotal in promoting immune cell homeostasis. This work aimed to evaluate the role of Gal-1 during a lipopolysaccharide (LPS)-induced-inflammatory milieu.
Method of Study
Using an ex vivo culture with two independent compartments, human fetal membranes at term were pretreated with 40 and 80 ng/mL of Gal-1, then to reproduce an intraamniotic inflammation, the fetal side of membranes was stimulated with 500 ng/mL of LPS for 24 h. The concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP1), macrophage inflammatory protein (MIP1) α, regulated upon activation normal T cell expressed and secreted (RANTES), and matrix metalloproteinase (MMP)-9 were measured in both amnion and choriodecidua compartments.
Results
In a tissue-specific fashion profile, pretreatment with the physiologic concentration of Gal-1 significantly diminished the LPS-dependent secretion of TNF-α, IL-1β, Il-6, MCP1, MIP1α, RANTES, and MMP-9.
Conclusion
Gal-1 elicits an anti-inflammatory effect on the human fetal membranes stimulated with LPS, which supports the hypothesis that Gal-1 is part of the immunomodulatory mechanisms intended to stop the harmful effect of inflammation of the maternal–fetal interface.
{"title":"Galectin-1 Elicits a Tissue-Specific Anti-Inflammatory and Anti-Degradative Effect Upon LPS-Induced Response in an Ex Vivo Model of Human Fetal Membranes Modeling an Intraamniotic Inflammation","authors":"Jazmin Hernández-Rodríguez, Jesús Pérez-Hernández, Pilar Flores-Espinosa, Andrea Olmos-Ortiz, Pilar Velazquez, Rodrigo Zamora-Escudero, Marcela Islas-López, Addy Cecilia Helguera-Repetto, Karla Hernández-Bones, Samara Rodríguez-Flores, Rodrigo Jiménez-Escutia, Amaury Fortanel-Fonseca, Arturo Flores-Pliego, Rosario Lopez-Vancell, Veronica Zaga-Clavellina","doi":"10.1111/aji.70016","DOIUrl":"10.1111/aji.70016","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Intrauterine infection is one of the most jeopardizing conditions associated with adverse outcomes, including preterm birth; however, multiple tolerance mechanisms operate at the maternal–fetal interface to avoid the rejection of the fetus. Among the factors that maintain the uterus as an immunoprivileged site, Galectin-1 (Gal-1), an immunomodulatory glycan-binding protein secreted by the maternal-fetal unit, is pivotal in promoting immune cell homeostasis. This work aimed to evaluate the role of Gal-1 during a lipopolysaccharide (LPS)-induced-inflammatory milieu.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Using an ex vivo culture with two independent compartments, human fetal membranes at term were pretreated with 40 and 80 ng/mL of Gal-1, then to reproduce an intraamniotic inflammation, the fetal side of membranes was stimulated with 500 ng/mL of LPS for 24 h. The concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP1), macrophage inflammatory protein (MIP1) α, regulated upon activation normal T cell expressed and secreted (RANTES), and matrix metalloproteinase (MMP)-9 were measured in both amnion and choriodecidua compartments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In a tissue-specific fashion profile, pretreatment with the physiologic concentration of Gal-1 significantly diminished the LPS-dependent secretion of TNF-α, IL-1β, Il-6, MCP1, MIP1α, RANTES, and MMP-9.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Gal-1 elicits an anti-inflammatory effect on the human fetal membranes stimulated with LPS, which supports the hypothesis that Gal-1 is part of the immunomodulatory mechanisms intended to stop the harmful effect of inflammation of the maternal–fetal interface.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11582940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685688","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}
Ai Zhao, Yawen Yang, Yijun Yang, Zhenjing Chi, Yanlan Sun
<div> <section> <h3> Background</h3> <p>Gestational diabetes mellitus (GDM) significantly risks maternal and neonatal health. Circular RNAs (circRNAs) regulate various diseases but their role in GDM is unclear. We investigated the involvement of circ-ADAM9 in GDM.</p> </section> <section> <h3> Methods</h3> <p>We analyzed circ-ADAM9 expression in GDM-related microarray data (GSE182737) and measured its levels in the blood of GDM patients. In a high-fat diet-induced GDM mouse model, we inhibited circ-ADAM9 expression and tracked blood glucose levels, serum insulin, lipid levels, placental apoptosis, and reactive oxygen species (ROS) levels. Pathological changes in pancreatic tissues and fetal outcomes were also examined. Molecular interactions were explored using bioinformatics tools and validated through luciferase assays, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting in high glucose (HG)-induced human trophoblast cells (HTR-8/SVneo). We further investigated the involvement of circ-ADAM9/miR-375/FPR2 axis in HG-induced injury in HTR-8/SVneo cells by assessing cell viability, apoptosis, ROS production, and antioxidant levels.</p> </section> <section> <h3> Results</h3> <p>Both GDM patients and GDM-induced mice exhibited a substantial upregulation of circ-ADAM9. Knockdown of circ-ADAM9 lowered blood glucose, alleviated insulin resistance, improved lipid metabolism, decreased placental apoptosis and ROS levels, and reduced pancreatic lesions in GDM mice. Circ-ADAM9 downregulation also improved fetal viability, weight, and crown-rump length. In HG-induced HTR-8/SVneo cells, circ-ADAM9 overexpression and miR-375 downregulation were evident. Overexpression of miR-375 inhibited circ-ADAM9 activity, substantiating their binding interaction. In GDM mice, circ-ADAM9 deficiency restored miR-375 expression. TargetScanHuman predicted and luciferase assays confirmed the miR-375-FPR2 interaction and elevated FPR2 levels in GDM mice were reduced by circ-ADAM9 silencing. In HG-induced HTR-8/SVneo cells, circ-ADAM9 knockdown restored cell viability, suppressed apoptosis and ROS levels, and enhanced antioxidant enzyme levels. These effects were reversed by miR-375 inhibition or FPR2 overexpression, suggesting circ-ADAM9 upregulates FPR2 expression by sponging miR-375 and modulating the MAPK pathway.</p> </section> <section> <h3> Conclusion</h3> <p>This study is the first to demonstrate the expression and function of circ-ADAM9 in the progression of GDM. Circ-ADAM9 downregulation ameliorates insulin resistance and placental injury in GDM by modulating the miR-375/FPR2 axis and inactivating the MAPK pathway, which may
{"title":"Circ-ADAM9 Knockdown Reduces Insulin Resistance and Placental Injury in Diabetic Mice via MAPK Pathway Inactivation","authors":"Ai Zhao, Yawen Yang, Yijun Yang, Zhenjing Chi, Yanlan Sun","doi":"10.1111/aji.70017","DOIUrl":"10.1111/aji.70017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gestational diabetes mellitus (GDM) significantly risks maternal and neonatal health. Circular RNAs (circRNAs) regulate various diseases but their role in GDM is unclear. We investigated the involvement of circ-ADAM9 in GDM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed circ-ADAM9 expression in GDM-related microarray data (GSE182737) and measured its levels in the blood of GDM patients. In a high-fat diet-induced GDM mouse model, we inhibited circ-ADAM9 expression and tracked blood glucose levels, serum insulin, lipid levels, placental apoptosis, and reactive oxygen species (ROS) levels. Pathological changes in pancreatic tissues and fetal outcomes were also examined. Molecular interactions were explored using bioinformatics tools and validated through luciferase assays, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting in high glucose (HG)-induced human trophoblast cells (HTR-8/SVneo). We further investigated the involvement of circ-ADAM9/miR-375/FPR2 axis in HG-induced injury in HTR-8/SVneo cells by assessing cell viability, apoptosis, ROS production, and antioxidant levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both GDM patients and GDM-induced mice exhibited a substantial upregulation of circ-ADAM9. Knockdown of circ-ADAM9 lowered blood glucose, alleviated insulin resistance, improved lipid metabolism, decreased placental apoptosis and ROS levels, and reduced pancreatic lesions in GDM mice. Circ-ADAM9 downregulation also improved fetal viability, weight, and crown-rump length. In HG-induced HTR-8/SVneo cells, circ-ADAM9 overexpression and miR-375 downregulation were evident. Overexpression of miR-375 inhibited circ-ADAM9 activity, substantiating their binding interaction. In GDM mice, circ-ADAM9 deficiency restored miR-375 expression. TargetScanHuman predicted and luciferase assays confirmed the miR-375-FPR2 interaction and elevated FPR2 levels in GDM mice were reduced by circ-ADAM9 silencing. In HG-induced HTR-8/SVneo cells, circ-ADAM9 knockdown restored cell viability, suppressed apoptosis and ROS levels, and enhanced antioxidant enzyme levels. These effects were reversed by miR-375 inhibition or FPR2 overexpression, suggesting circ-ADAM9 upregulates FPR2 expression by sponging miR-375 and modulating the MAPK pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study is the first to demonstrate the expression and function of circ-ADAM9 in the progression of GDM. Circ-ADAM9 downregulation ameliorates insulin resistance and placental injury in GDM by modulating the miR-375/FPR2 axis and inactivating the MAPK pathway, which may ","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685686","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}
Investigating the impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on female fertility and laboratory outcomes in patients undergoing assisted reproductive technology (ART) treatment who were initially uninfected but later became infected.
Methods of the Study
This self-controlled study included 197 patients who underwent repeated oocyte retrieval before and after SARS-CoV-2 infection between March 2021 and April 2023, of which 117 used the same ovarian stimulation protocol within a consistent age range. We evaluated the ovarian reserve, ovarian response, and laboratory outcomes in patients before and after SARS-CoV-2 infection.
Results
The ovarian reserve (follicle-stimulating hormone [FSH], luteinizing hormone [LH], estrogen [E2], anti-Müllerian hormone [AMH], antral follicle count [AFC]), ovarian response (total Gn dosage, duration of Gn administration, number of follicles ≥14 mm on trigger day, number of retrieved oocytes), and laboratory outcomes (cleavage stage good-quality embryo rate, blastocyst formation rate, and cycle freezing rate) showed no significant differences before and after SARS-CoV-2 infection in 117 patients (p > 0.05). When stratified by age, the ≤ 35 years group showed a higher two pronuclei (2PN) fertilization rate post-infection, while the >35 years group had increased mature metaphase II (MII) oocyte and blastocyst stage good-quality embryo rates. Additionally, upon stratified by the time interval between SARS-CoV-2 infection and ART treatment, in the ≤ 3 months group, there was an increased post-infection MII oocyte rate, 2PN fertilization rate, and blastocyst stage good-quality embryo rate. Meanwhile, no significant differences were found in any indicators when the interval exceeded three months.
Conclusion
Our study suggested that undergoing IVF/ICSI treatment after recovering from COVID-19 may not adversely affect female fertility and laboratory outcomes.
{"title":"Impact of Omicron Variant Infection on Female Fertility and Laboratory Outcomes: A Self-Controlled Study","authors":"Yu-Ling Hu, Yong-Jia Zhang, Xing-Yu Lv, Rui-Ling Liu, Zhao-Hui Zhong, Li-Juan Fu, Mei-Hua Bao, Li-Hong Geng, Hai-Jiao Xu, Shao-Min Yu, Yu-Bin Ding","doi":"10.1111/aji.70012","DOIUrl":"10.1111/aji.70012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Investigating the impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on female fertility and laboratory outcomes in patients undergoing assisted reproductive technology (ART) treatment who were initially uninfected but later became infected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods of the Study</h3>\u0000 \u0000 <p>This self-controlled study included 197 patients who underwent repeated oocyte retrieval before and after SARS-CoV-2 infection between March 2021 and April 2023, of which 117 used the same ovarian stimulation protocol within a consistent age range. We evaluated the ovarian reserve, ovarian response, and laboratory outcomes in patients before and after SARS-CoV-2 infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The ovarian reserve (follicle-stimulating hormone [FSH], luteinizing hormone [LH], estrogen [E<sub>2</sub>], anti-Müllerian hormone [AMH], antral follicle count [AFC]), ovarian response (total Gn dosage, duration of Gn administration, number of follicles ≥14 mm on trigger day, number of retrieved oocytes), and laboratory outcomes (cleavage stage good-quality embryo rate, blastocyst formation rate, and cycle freezing rate) showed no significant differences before and after SARS-CoV-2 infection in 117 patients (<i>p</i> > 0.05). When stratified by age, the ≤ 35 years group showed a higher two pronuclei (2PN) fertilization rate post-infection, while the >35 years group had increased mature metaphase II (MII) oocyte and blastocyst stage good-quality embryo rates. Additionally, upon stratified by the time interval between SARS-CoV-2 infection and ART treatment, in the ≤ 3 months group, there was an increased post-infection MII oocyte rate, 2PN fertilization rate, and blastocyst stage good-quality embryo rate. Meanwhile, no significant differences were found in any indicators when the interval exceeded three months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study suggested that undergoing IVF/ICSI treatment after recovering from COVID-19 may not adversely affect female fertility and laboratory outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612396","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}
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.
{"title":"Cell Communications Between GCs and Macrophages Contribute to the Residence of Macrophage in Preovulatory Follicles","authors":"Huihua Wu, Ce Zhang, Rui Zhu, Qingxia Meng, Fuxin Wang, Liang Gao, Nannan Zhao, Hong Li, Mingqing Li","doi":"10.1111/aji.70009","DOIUrl":"10.1111/aji.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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 (<i>p</i> < 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 (<i>p</i> < 0.01). Progesterone increased the synthesis of FN1 in KGN cells (<i>p</i> < 0.0001) and was suppressed by the elimination of PGR. The adhesion effect of KGN cells on macrophages was enhanced by progesterone (<i>p</i> < 0.0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612394","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号