Meryam Sugulle, Bendik S. Fiskå, Daniel Pitz Jacobsen, Heidi Elisabeth Fjeldstad, Anne Cathrine Staff
In this review, we summarize how an increasingly stressed and aging placenta contributes to the maternal clinical signs of preeclampsia, a potentially lethal pregnancy complication. The pathophysiology of preeclampsia has been conceptualized in the two-stage model. Originally, highlighting the importance of poor placentation for early-onset preeclampsia, the revised two-stage model explains late-onset preeclampsia as well, which is often preceded by normal placentation. We discuss how cellular senescence in the placenta may fit with the framework of the revised two-stage model of preeclampsia pathophysiology and summarize potential cellular and molecular mechanisms, including effects on placental and maternal endothelial function. Cellular senescence may occur in response to inflammatory processes and oxidative, mitochondrial, or endoplasmic reticulum stress and chronic stress induce accelerated, premature placental senescence. In preeclampsia, both circulating and tissue-based senescence markers are present. We suggest that aspirin prophylaxis, commonly recommended from the first trimester onward for women at risk of preeclampsia, may affect placentation and possibly mechanisms of placental senescence, thus attenuating the risk of preeclampsia developing clinically. We propose that biomarkers of placental dysfunction and senescence may contribute to altered preventive strategies, including discontinuation of aspirin at week 24–28 depending on placenta-associated biomarker risk stratification.
{"title":"Placental Senescence and the Two-Stage Model of Preeclampsia","authors":"Meryam Sugulle, Bendik S. Fiskå, Daniel Pitz Jacobsen, Heidi Elisabeth Fjeldstad, Anne Cathrine Staff","doi":"10.1111/aji.13904","DOIUrl":"10.1111/aji.13904","url":null,"abstract":"<p>In this review, we summarize how an increasingly stressed and aging placenta contributes to the maternal clinical signs of preeclampsia, a potentially lethal pregnancy complication. The pathophysiology of preeclampsia has been conceptualized in the two-stage model. Originally, highlighting the importance of poor placentation for early-onset preeclampsia, the revised two-stage model explains late-onset preeclampsia as well, which is often preceded by normal placentation. We discuss how cellular senescence in the placenta may fit with the framework of the revised two-stage model of preeclampsia pathophysiology and summarize potential cellular and molecular mechanisms, including effects on placental and maternal endothelial function. Cellular senescence may occur in response to inflammatory processes and oxidative, mitochondrial, or endoplasmic reticulum stress and chronic stress induce accelerated, premature placental senescence. In preeclampsia, both circulating and tissue-based senescence markers are present. We suggest that aspirin prophylaxis, commonly recommended from the first trimester onward for women at risk of preeclampsia, may affect placentation and possibly mechanisms of placental senescence, thus attenuating the risk of preeclampsia developing clinically. We propose that biomarkers of placental dysfunction and senescence may contribute to altered preventive strategies, including discontinuation of aspirin at week 24–28 depending on placenta-associated biomarker risk stratification.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.13904","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756666","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}
Achieving pregnancy through in vitro fertilization (IVF) remains a challenge, with less than one-third of women succeeding. There is a pressing need for reliable predictive tools to assess the likelihood of post-IVF pregnancy. While some serum inflammatory biomarkers have been investigated for their predictive potential, substantial knowledge gaps persist. This study examined the utility of different inflammatory markers in predicting IVF outcomes.
Method of Study
Inflammatory markers including the white blood cell count, neutrophil-to-lymphocyte ratio (NLR), platelet count, mean platelet volume, platelet distribution width, platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), erythrocyte sedimentation rate, and vitamin D3 were assessed. Study outcomes were chemical pregnancy (positive serum beta-human chorionic gonadotropin 2 weeks post-embryo transfer), clinical pregnancy (detection of pregnancy sac via transvaginal ultrasonography), and viable pregnancy (detection of fetal heart rate). Univariate and multivariate logistic regression analyses were conducted, with multivariate analysis incorporating age, body mass index, infertility duration, type, and etiology, as well as all studied serum inflammatory markers, embryo count, stage, quality, and endometrial thickness.
Results
Lower NLR (p < 0.001, odds ratio [OR] = 0.372 [0.247–0.559]) and CRP (p = 0.035, odds ratio = 0.956 [0.916–0.997]) predicted chemical pregnancy in univariate analysis, with NLR maintaining significance in multivariate analysis (p = 0.022, OR = 0.319 [0.120–0.848]). Lower NLR (p < 0.001, OR = 0.309 [0.198–0.482]) and PLR (p = 0.013, OR = 0.994 [0.990–0.999]) predicted clinical pregnancy, with NLR surviving multivariate analysis (p = 0.005, OR = 0.217 [0.075–0.626]). Lower NLR (p < 0.001, OR = 0.320 [0.198–0.516]) also predicted viable pregnancy, maintaining statistical significance in multivariate analysis (p = 0.002, OR = 0.177 [0.058–0.541]). Other studied inflammatory markers did not predict IVF outcomes.
Conclusions
NLR emerged as a robust independent predictor of pregnancy attainment after IVF.
{"title":"Predicting the Outcomes of In Vitro Fertilization Using Baseline Maternal Serum Inflammatory Markers: A Retrospective Cohort Study","authors":"Sedigheh Hantoushzadeh, Marzie Poorabdoli, Mohammadamin Parsaei, Nikan Zargarzadeh, Masoumeh Masoumi, Saeedeh Eslami Khotbesara, Azadeh Tarafdari","doi":"10.1111/aji.13900","DOIUrl":"10.1111/aji.13900","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Achieving pregnancy through in vitro fertilization (IVF) remains a challenge, with less than one-third of women succeeding. There is a pressing need for reliable predictive tools to assess the likelihood of post-IVF pregnancy. While some serum inflammatory biomarkers have been investigated for their predictive potential, substantial knowledge gaps persist. This study examined the utility of different inflammatory markers in predicting IVF outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Inflammatory markers including the white blood cell count, neutrophil-to-lymphocyte ratio (NLR), platelet count, mean platelet volume, platelet distribution width, platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), erythrocyte sedimentation rate, and vitamin D<sub>3</sub> were assessed. Study outcomes were chemical pregnancy (positive serum beta-human chorionic gonadotropin 2 weeks post-embryo transfer), clinical pregnancy (detection of pregnancy sac via transvaginal ultrasonography), and viable pregnancy (detection of fetal heart rate). Univariate and multivariate logistic regression analyses were conducted, with multivariate analysis incorporating age, body mass index, infertility duration, type, and etiology, as well as all studied serum inflammatory markers, embryo count, stage, quality, and endometrial thickness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Lower NLR (<i>p</i> < 0.001, odds ratio [OR] = 0.372 [0.247–0.559]) and CRP (<i>p</i> = 0.035, odds ratio = 0.956 [0.916–0.997]) predicted chemical pregnancy in univariate analysis, with NLR maintaining significance in multivariate analysis (<i>p</i> = 0.022, OR = 0.319 [0.120–0.848]). Lower NLR (<i>p</i> < 0.001, OR = 0.309 [0.198–0.482]) and PLR (<i>p</i> = 0.013, OR = 0.994 [0.990–0.999]) predicted clinical pregnancy, with NLR surviving multivariate analysis (<i>p</i> = 0.005, OR = 0.217 [0.075–0.626]). Lower NLR (<i>p</i> < 0.001, OR = 0.320 [0.198–0.516]) also predicted viable pregnancy, maintaining statistical significance in multivariate analysis (<i>p</i> = 0.002, OR = 0.177 [0.058–0.541]). Other studied inflammatory markers did not predict IVF outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>NLR emerged as a robust independent predictor of pregnancy attainment after IVF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756645","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}
Li Zhang, Lei Zhu, Pengfei Che, Xiaoyan Sun, Yupeng Guo, Mingjie Gao, Junjie Wang
Problem
Adenomyosis (AM) is associated with immune response and inflammation. However, the role of T cell subsets in AM development has not been thoroughly understood.
Method of Study
Patients with focal or diffuse AM were recruited. Serum cytokines were quantified by enzyme-linked immunosorbent assay (ELISA). Different T cell subsets in the blood and ectopic endometrium were determined by flow cytometry.
Results
Serum interleukin-6 (IL-6) and macrophage-colony-stimulating factor (GM-CSF) were increased in patients with focal or diffuse AM before focused ultrasound ablation surgery (FUAS), but not after FUAS. Compared with the healthy control, the frequencies of CD8+ interferon-gamma (IFN-γ)-expressing cytotoxic T lymphocytes (CTLs), interleukin-17A (IL-17A)-expressing Tc17 cells, CD4+ T helper 1 (Th1) cells, and GM-CSF-expressing T helper (ThGM) cells were up-regulated in the blood of patients with AM, especially those with diffuse AM. However, these changes were eradicated after FUAS. Meanwhile, the frequencies of these T cell subsets were positively correlated with the CA-125 level. Furthermore, these T cell subsets were also increased in ectopic endometrium.
Conclusions
Our study delineates for the first time the presence of CTLs, Tc17 cells, Th1, and ThGM cells in the blood and ectopic endometrium in AM. The results imply that T cell response might impact AM development.
问题：子宫腺肌症（AM）与免疫反应和炎症有关。然而，T细胞亚群在AM发病中的作用尚未得到彻底了解：研究方法：招募局灶性或弥漫性AM患者。研究方法：招募局灶性或弥漫性 AM 患者，用酶联免疫吸附试验（ELISA）定量检测血清细胞因子。通过流式细胞术测定血液和异位子宫内膜中不同的 T 细胞亚群：结果：聚焦超声消融术（FUAS）前，局灶性或弥漫性AM患者血清白细胞介素-6（IL-6）和巨噬细胞-集落刺激因子（GM-CSF）升高，而聚焦超声消融术后则没有升高。与健康对照组相比，AM 患者血液中表达细胞毒性 T 淋巴细胞（CTLs）的 CD8+ γ 干扰素（IFN-γ）、表达白细胞介素-17A（IL-17A）的 Tc17 细胞、CD4+ T 辅助细胞 1（Th1）和表达 GM-CSF 的 T 辅助细胞（ThGM）的频率上调，尤其是弥漫性 AM 患者。然而，这些变化在 FUAS 后被消除。同时，这些 T 细胞亚群的频率与 CA-125 水平呈正相关。此外，这些T细胞亚群在异位子宫内膜中也有所增加：我们的研究首次描述了 AM 患者血液和异位子宫内膜中 CTLs、Tc17 细胞、Th1 和 ThGM 细胞的存在。研究结果表明，T细胞反应可能会影响AM的发育。
{"title":"Cytotoxic T Lymphocytes, Tc17 Cells, Th1 Cells, and ThGM Cells are Increased in the Blood and Ectopic Endometrium of Patients With Adenomyosis","authors":"Li Zhang, Lei Zhu, Pengfei Che, Xiaoyan Sun, Yupeng Guo, Mingjie Gao, Junjie Wang","doi":"10.1111/aji.13901","DOIUrl":"10.1111/aji.13901","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Adenomyosis (AM) is associated with immune response and inflammation. However, the role of T cell subsets in AM development has not been thoroughly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Patients with focal or diffuse AM were recruited. Serum cytokines were quantified by enzyme-linked immunosorbent assay (ELISA). Different T cell subsets in the blood and ectopic endometrium were determined by flow cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Serum interleukin-6 (IL-6) and macrophage-colony-stimulating factor (GM-CSF) were increased in patients with focal or diffuse AM before focused ultrasound ablation surgery (FUAS), but not after FUAS. Compared with the healthy control, the frequencies of CD8<sup>+</sup> interferon-gamma (IFN-γ)-expressing cytotoxic T lymphocytes (CTLs), interleukin-17A (IL-17A)-expressing Tc17 cells, CD4<sup>+</sup> T helper 1 (Th1) cells, and GM-CSF-expressing T helper (ThGM) cells were up-regulated in the blood of patients with AM, especially those with diffuse AM. However, these changes were eradicated after FUAS. Meanwhile, the frequencies of these T cell subsets were positively correlated with the CA-125 level. Furthermore, these T cell subsets were also increased in ectopic endometrium.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study delineates for the first time the presence of CTLs, Tc17 cells, Th1, and ThGM cells in the blood and ectopic endometrium in AM. The results imply that T cell response might impact AM development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750922","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}
Lipopolysaccharide (LPS) from gram-negative bacteria has reportedly been associated with infectious diseases like metritis, which has a substantial adverse effect on animal reproductive performance and causes serious financial losses for the dairy sector. The current work aimed to establish the impact of LPS on in vitro oocyte maturation and subsequent in vitro developmental competence of oocytes, as well as to investigate the explanatory molecular mechanism underlying this effect.
Method of Study
Buffalo cumulus-oocyte complexes (COCs) were challenged with 0, 5, 10 and 20 µg/mL LPS during IVM followed by IVF and IVC. Cytoplasmic and nuclear maturation, cleavage and blastocyst rate, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP, ΔΨm) and transcript abundance of genes related to inflammation, antioxidation and apoptosis were evaluated.
Results
The maturation and subsequent embryonic development competency were found to be significantly (p ≤ 0.05) reduced with the addition of 10 and 20 µg/mL LPS to IVM media. ROS production accompanied by a decreased ΔΨm was recorded in LPS-treated oocytes in comparison to the control group (p ≤ 0.05). Our results were further supported by the transcriptional expression of proinflammatory (TLR4, CD14 and RPS27A) and apoptotic gene (Caspase 3) which were found to be significantly increased while antioxidant genes (SOD2 and GPX1) were decreased significantly in matured oocytes and blastocyst after LPS exposure.
Conclusions
The deleterious effects of LPS are mediated through ROS generation, which triggers inflammatory processes via the TLR4 pathway and impairs oocyte maturation and subsequent embryonic development.
{"title":"LPS-Induced Mitochondrial Dysfunction Reduces Oocyte Maturation and Developmental Competence of Buffalo Embryos via ROS Mediated TLR4 Signalling","authors":"Sujata Jinagal, Ravi Dutt, Maninder Sharma, Meeti Punetha, Sheetal Saini, Swati Thakur, Suman Chaudhary, Pradeep Kumar, Prem Singh Yadav, Tirth Kumar Datta, Dharmendra Kumar","doi":"10.1111/aji.13902","DOIUrl":"10.1111/aji.13902","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Lipopolysaccharide (LPS) from gram-negative bacteria has reportedly been associated with infectious diseases like metritis, which has a substantial adverse effect on animal reproductive performance and causes serious financial losses for the dairy sector. The current work aimed to establish the impact of LPS on in vitro oocyte maturation and subsequent in vitro developmental competence of oocytes, as well as to investigate the explanatory molecular mechanism underlying this effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Buffalo cumulus-oocyte complexes (COCs) were challenged with 0, 5, 10 and 20 µg/mL LPS during IVM followed by IVF and IVC. Cytoplasmic and nuclear maturation, cleavage and blastocyst rate, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP, ΔΨm) and transcript abundance of genes related to inflammation, antioxidation and apoptosis were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The maturation and subsequent embryonic development competency were found to be significantly (<i>p</i> ≤ 0.05) reduced with the addition of 10 and 20 µg/mL LPS to IVM media. ROS production accompanied by a decreased ΔΨm was recorded in LPS-treated oocytes in comparison to the control group (<i>p</i> ≤ 0.05). Our results were further supported by the transcriptional expression of proinflammatory (TLR4, CD14 and RPS27A) and apoptotic gene (Caspase 3) which were found to be significantly increased while antioxidant genes (SOD2 and GPX1) were decreased significantly in matured oocytes and blastocyst after LPS exposure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The deleterious effects of LPS are mediated through ROS generation, which triggers inflammatory processes via the TLR4 pathway and impairs oocyte maturation and subsequent embryonic development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750923","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}
To investigate the role of inflammatory markers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR), c-reactive protein (CRP) to albumin ratio (CAR), fibrinogen to albumin ratio (FAR), and fibrinogen to CRP ratio (FCR) in predicting the latency period (≤72 vs. >72 hours) before preterm birth.
Materials and Methods
In a retrospective study, we assessed 135 patients meeting the specified criteria with signs of preterm labor (<34 weeks). The patients were categorized into two groups: 71 patients giving birth within 72 h (latency ≤ 72 h) and 64 patients giving birth after 72 h (latency > 72 h). We examined the demographic and medical characteristics and perinatal outcomes of all participants. Categorical variables between groups were compared using the Chi-square test. The Student's t-test was utilized for normally distributed continuous variables, and the Mann–Whitney U test was applied for non-normally distributed data. Receiver operating characteristic (ROC) curve analysis was conducted to identify the optimal cut-off levels for inflammatory markers in predicting the latency period before birth.
Results
Among the parameters examined, significant differences were observed between the groups only in terms of CAR and FCR. While CAR showed a significantly higher value in the group with latency period ≤72 h (0.537 ± 1.239 vs. 0.247 ± 0.325, p = 0.022), FCR showed a significantly lower value in the group with latency period ≤72 h (63.58 (2.99–1165) vs. 88.93 (9.35–1165), p = 0.013). The identified cut-off value for CAR was 0.190, providing a sensitivity of 57.7% and a specificity of 56.3% (p = 0.022). The cut-off value for FCR was 71.67, with a sensitivity of 42.3% and a specificity of 42.2% (p = 0.013).
Conclusions
The CAR and the FCR, serving as predictive markers for preterm labor, may offer a simple, cost-effective, and easily accessible approach, particularly in resource-limited settings.
目的研究炎症指标（包括中性粒细胞与淋巴细胞比值（NLR）、血小板与淋巴细胞比值（PLR）、单核细胞与淋巴细胞比值（MLR）、c 反应蛋白（CRP）与白蛋白比值（CAR）、纤维蛋白原与白蛋白比值（FAR）、纤维蛋白原与 CRP 比值（FCR））在预测早产前潜伏期（≤72 小时与 >72 小时）中的作用：在一项回顾性研究中，我们对 135 名符合特定标准且有早产迹象（72 小时）的患者进行了评估。我们检查了所有参与者的人口统计学特征、医学特征和围产期结局。组间分类变量的比较采用卡方检验（Chi-square test）。对正态分布的连续变量采用学生 t 检验，对非正态分布的数据采用 Mann-Whitney U 检验。为了确定炎症标志物预测产前潜伏期的最佳临界值，进行了接收者操作特征曲线（ROC）分析：在检查的各项参数中，只有 CAR 和 FCR 在组间存在显著差异。潜伏期≤72小时组的CAR值明显更高（0.537 ± 1.239 vs. 0.247 ± 0.325，p = 0.022），而潜伏期≤72小时组的FCR值明显更低（63.58 (2.99-1165) vs. 88.93 (9.35-1165)，p = 0.013）。确定的 CAR 临界值为 0.190，灵敏度为 57.7%，特异度为 56.3%（p = 0.022）。FCR 的临界值为 71.67，灵敏度为 42.3%，特异度为 42.2%（p = 0.013）：作为早产的预测指标，CAR 和 FCR 可提供一种简单、经济、易行的方法，尤其是在资源有限的环境中。
{"title":"The Efficacy of C-Reactive Protein (CRP) to Albumin Ratio (CAR) and Fibrinogen to CRP Ratio (FCR) in Predicting the Latent Period of Preterm Labor","authors":"Zeynep Seyhanli, Burak Bayraktar, Betul Tokgoz Cakir, Mevlut Bucak, Gulsan Karabay, Gizem Aktemur, Ayse Yigit, Kadriye Yakut Yucel, Zehra Vural Yılmaz","doi":"10.1111/aji.13899","DOIUrl":"10.1111/aji.13899","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate the role of inflammatory markers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR), c-reactive protein (CRP) to albumin ratio (CAR), fibrinogen to albumin ratio (FAR), and fibrinogen to CRP ratio (FCR) in predicting the latency period (≤72 vs. >72 hours) before preterm birth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In a retrospective study, we assessed 135 patients meeting the specified criteria with signs of preterm labor (<34 weeks). The patients were categorized into two groups: 71 patients giving birth within 72 h (latency ≤ 72 h) and 64 patients giving birth after 72 h (latency > 72 h). We examined the demographic and medical characteristics and perinatal outcomes of all participants. Categorical variables between groups were compared using the Chi-square test. The Student's <i>t-</i>test was utilized for normally distributed continuous variables, and the Mann–Whitney <i>U</i> test was applied for non-normally distributed data. Receiver operating characteristic (ROC) curve analysis was conducted to identify the optimal cut-off levels for inflammatory markers in predicting the latency period before birth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the parameters examined, significant differences were observed between the groups only in terms of CAR and FCR. While CAR showed a significantly higher value in the group with latency period ≤72 h (0.537 ± 1.239 vs. 0.247 ± 0.325, <i>p</i> = 0.022), FCR showed a significantly lower value in the group with latency period ≤72 h (63.58 (2.99–1165) vs. 88.93 (9.35–1165), <i>p</i> = 0.013). The identified cut-off value for CAR was 0.190, providing a sensitivity of 57.7% and a specificity of 56.3% (<i>p</i> = 0.022). The cut-off value for FCR was 71.67, with a sensitivity of 42.3% and a specificity of 42.2% (<i>p</i> = 0.013).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The CAR and the FCR, serving as predictive markers for preterm labor, may offer a simple, cost-effective, and easily accessible approach, particularly in resource-limited settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750841","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}
The vaginal microbiome has a substantial role in the occurrence of preterm birth (PTB), which contributes substantially to neonatal mortality worldwide. However, current bioinformatics approaches mostly concentrate on the taxonomic classification and functional profiling of the microbiome, limiting their abilities to elucidate the complex factors that contribute to PTB.
Method of study
A total of 3757 vaginal microbiome 16S rRNA samples were obtained from five publicly available datasets. The samples were divided into two categories based on pregnancy outcome: preterm birth (PTB) (N = 966) and term birth (N = 2791). Additionally, the samples were further categorized based on the participants’ race and trimester. The 16S rRNA reads were subjected to taxonomic classification and functional profiling using the Parallel-META 3 software in Ubuntu environment. The obtained abundances were analyzed using an integrated systems biology and machine learning approach to determine the key microbes, pathways, and genes that contribute to PTB. The resulting features were further subjected to statistical analysis to identify the top nine features with the greatest effect sizes.
Results
We identified nine significant features, namely Shuttleworthia, Megasphaera, Sneathia, proximal tubule bicarbonate reclamation pathway, systemic lupus erythematosus pathway, transcription machinery pathway, lepA gene, pepX gene, and rpoD gene. Their abundance variations were observed through the trimesters.
Conclusions
Vaginal infections caused by Shuttleworthia, Megasphaera, and Sneathia and altered small metabolite biosynthesis pathways such as lipopolysaccharide folate and retinal may increase the susceptibility to PTB. The identified organisms, genes, pathways, and their networks may be specifically targeted for the treatment of bacterial infections that increase PTB risk.
{"title":"Biomarker Identification for Preterm Birth Susceptibility: Vaginal Microbiome Meta-Analysis Using Systems Biology and Machine Learning Approaches","authors":"Sudeepti Kulshrestha, Priyanka Narad, Brojen Singh, Somnath S. Pai, Pooja Vijayaraghavan, Ansh Tandon, Payal Gupta, Deepak Modi, Abhishek Sengupta","doi":"10.1111/aji.13905","DOIUrl":"10.1111/aji.13905","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>The vaginal microbiome has a substantial role in the occurrence of preterm birth (PTB), which contributes substantially to neonatal mortality worldwide. However, current bioinformatics approaches mostly concentrate on the taxonomic classification and functional profiling of the microbiome, limiting their abilities to elucidate the complex factors that contribute to PTB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of study</h3>\u0000 \u0000 <p>A total of 3757 vaginal microbiome 16S rRNA samples were obtained from five publicly available datasets. The samples were divided into two categories based on pregnancy outcome: preterm birth (PTB) (<i>N</i> = 966) and term birth (<i>N</i> = 2791). Additionally, the samples were further categorized based on the participants’ race and trimester. The 16S rRNA reads were subjected to taxonomic classification and functional profiling using the Parallel-META 3 software in Ubuntu environment. The obtained abundances were analyzed using an integrated systems biology and machine learning approach to determine the key microbes, pathways, and genes that contribute to PTB. The resulting features were further subjected to statistical analysis to identify the top nine features with the greatest effect sizes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified nine significant features, namely <i>Shuttleworthia</i>, <i>Megasphaera</i>, <i>Sneathia</i>, proximal tubule bicarbonate reclamation pathway, systemic lupus erythematosus pathway, transcription machinery pathway, <i>lepA</i> gene, <i>pepX</i> gene, and <i>rpoD</i> gene. Their abundance variations were observed through the trimesters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Vaginal infections caused by <i>Shuttleworthia</i>, <i>Megasphaera</i>, and <i>Sneathia</i> and altered small metabolite biosynthesis pathways such as lipopolysaccharide folate and retinal may increase the susceptibility to PTB. The identified organisms, genes, pathways, and their networks may be specifically targeted for the treatment of bacterial infections that increase PTB risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733333","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}
Xi Wang, Corbin A. Shields, Deanna Thompson, Jie McKay, Rachel Wilson, Marcus K. Robbins, Hannah Glenn, Molly Fontenot, Jan M. Williams, Denise C. Cornelius
Problem
Preeclampsia (PE) is a hypertensive pregnancy disorder that is a leading cause of maternal and fetal morbidity and mortality characterized by maternal vascular dysfunction, oxidative stress, chronic immune activation, and excessive inflammation. No cure exists beyond delivery of the fetal–placental unit and the mechanisms driving pathophysiology are not fully understood. However, aberrant immune responses have been extensively characterized in clinical studies and shown to mediate PE pathophysiology in animal studies. One pathway that may mediate aberrant immune responses in PE is deficiencies in the IL-33 signaling pathway. In this study, we aim to investigate the impact of IL-33 signaling inhibition on cNK, TH17, and TReg populations, vascular function, and maternal blood pressure during pregnancy.
Method of Study
In this study, IL-33 signaling was inhibited using two different methods: intraperitoneal administration of recombinant ST2 (which acts as a decoy receptor for IL-33) and administration of a specific IL-33 neutralizing antibody. Maternal blood pressure, uterine artery resistance index, renal and placental oxidative stress, cNK, TH17, and TReg populations, various cytokines, and pre-proendothelin-1 levels were measured.
Results
IL-33 signaling inhibition increased maternal blood pressure, uterine artery resistance, placental and renal oxidative stress. IL-33 signaling inhibition also increased placental cNK and TH17 and renal TH17 cells while decreasing placental TReg populations. IL-33 neutralization increased circulating cNK and TH17s and decreased circulating TRegs in addition to increasing pre-proendothelin-1 levels.
Conclusions
Data presented in this study demonstrate a role for IL-33 signaling in controlling vascular function and maternal blood pressure during pregnancy possibly by mediating innate and adaptive immune inflammatory responses, identifying the IL-33 signaling pathway as a potential therapeutic target for managing preeclampsia.
{"title":"IL-33 Signaling Inhibition Leads to a Preeclampsia-Like Phenotype in Pregnant Rats","authors":"Xi Wang, Corbin A. Shields, Deanna Thompson, Jie McKay, Rachel Wilson, Marcus K. Robbins, Hannah Glenn, Molly Fontenot, Jan M. Williams, Denise C. Cornelius","doi":"10.1111/aji.13895","DOIUrl":"10.1111/aji.13895","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Preeclampsia (PE) is a hypertensive pregnancy disorder that is a leading cause of maternal and fetal morbidity and mortality characterized by maternal vascular dysfunction, oxidative stress, chronic immune activation, and excessive inflammation. No cure exists beyond delivery of the fetal–placental unit and the mechanisms driving pathophysiology are not fully understood. However, aberrant immune responses have been extensively characterized in clinical studies and shown to mediate PE pathophysiology in animal studies. One pathway that may mediate aberrant immune responses in PE is deficiencies in the IL-33 signaling pathway. In this study, we aim to investigate the impact of IL-33 signaling inhibition on cNK, T<sub>H</sub>17, and T<sub>Reg</sub> populations, vascular function, and maternal blood pressure during pregnancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>In this study, IL-33 signaling was inhibited using two different methods: intraperitoneal administration of recombinant ST2 (which acts as a decoy receptor for IL-33) and administration of a specific IL-33 neutralizing antibody. Maternal blood pressure, uterine artery resistance index, renal and placental oxidative stress, cNK, T<sub>H</sub>17, and T<sub>Reg</sub> populations, various cytokines, and pre-proendothelin-1 levels were measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>IL-33 signaling inhibition increased maternal blood pressure, uterine artery resistance, placental and renal oxidative stress. IL-33 signaling inhibition also increased placental cNK and T<sub>H</sub>17 and renal T<sub>H</sub>17 cells while decreasing placental T<sub>Reg</sub> populations. IL-33 neutralization increased circulating cNK and T<sub>H</sub>17s and decreased circulating T<sub>Reg</sub>s in addition to increasing pre-proendothelin-1 levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Data presented in this study demonstrate a role for IL-33 signaling in controlling vascular function and maternal blood pressure during pregnancy possibly by mediating innate and adaptive immune inflammatory responses, identifying the IL-33 signaling pathway as a potential therapeutic target for managing preeclampsia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141598104","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}
Marwan Ma'ayeh, Jessica A. de Voest, Brenna L. Hughes, William A. Grobman, George R. Saade, Tracy A. Manuck, Monica Longo, Hyagriv N. Simhan, Dwight J. Rouse, Hector Mendez-Figueroa, Cynthia Gyamfi-Bannerman, Jennifer L. Bailit, Maged M. Costantine, Harish M. Sehdev, Alan T. N. Tita, Torri D. Metz, for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network
Background
Recent data in nonpregnant individuals suggest a protective effect of influenza vaccination against SARS-CoV-2 infection and its severity.
Objectives
Our primary objective was to evaluate whether influenza vaccination was associated with COVID-19 severity and pregnancy and neonatal outcomes among those infected with SARS-CoV-2. The secondary objective was to examine the association between influenza vaccination and SARS-CoV-2 infection.
Study Design
Secondary analysis of a multicenter retrospective cohort of pregnant people who tested positive for SARS-CoV-2 between March and August 2020, and a cohort of random deliveries during the same time period. The associations between 2019 influenza vaccination and the primary outcome of moderate-to-critical COVID-19 as well as maternal and perinatal outcomes were examined among all people who tested positive for SARS-CoV-2 between March and August 2020. The association between 2019 influenza vaccination and having a positive SARS-CoV-2 test was examined among a cohort of individuals who delivered on randomly selected dates between March and August 2020. Univariable and multivariable analyses were performed.
Results
Of 2325 people who tested positive for SARS-CoV-2, 1068 (45.9%) were vaccinated against influenza in 2019. Those who received the influenza vaccine were older, leaner, more likely to have private insurance, and identify as White or Hispanic. They were less likely to smoke tobacco and identify as Black. Overall, 419 (18.0%) had moderate, 193 (8.3%) severe, and 52 (2.2%) critical COVID-19. There was no association between influenza vaccination and moderate-to-critical COVID-19 (29.2% vs. 28.0%, adjusted OR 1.10, 95% CI 0.90–1.34) or adverse maternal and perinatal outcomes among those who tested positive. Of 8152 people who delivered in 2020, 4658 (57.1%) received the influenza vaccine. Prior vaccination was not associated with a difference in the odds of SARS-CoV-2 infection (3.8% vs. 4.2%, adjusted OR 0.94, 95% CI 0.74–1.19).
Conclusion
Prior influenza vaccination was not associated with decreased severity of COVID-19 or lower odds of SARS-CoV-2 infection in pregnancy.
{"title":"Association Between Influenza Vaccination and SARS-CoV-2 Infection","authors":"Marwan Ma'ayeh, Jessica A. de Voest, Brenna L. Hughes, William A. Grobman, George R. Saade, Tracy A. Manuck, Monica Longo, Hyagriv N. Simhan, Dwight J. Rouse, Hector Mendez-Figueroa, Cynthia Gyamfi-Bannerman, Jennifer L. Bailit, Maged M. Costantine, Harish M. Sehdev, Alan T. N. Tita, Torri D. Metz, for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network","doi":"10.1111/aji.13896","DOIUrl":"10.1111/aji.13896","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Recent data in nonpregnant individuals suggest a protective effect of influenza vaccination against SARS-CoV-2 infection and its severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Our primary objective was to evaluate whether influenza vaccination was associated with COVID-19 severity and pregnancy and neonatal outcomes among those infected with SARS-CoV-2. The secondary objective was to examine the association between influenza vaccination and SARS-CoV-2 infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Study Design</h3>\u0000 \u0000 <p>Secondary analysis of a multicenter retrospective cohort of pregnant people who tested positive for SARS-CoV-2 between March and August 2020, and a cohort of random deliveries during the same time period. The associations between 2019 influenza vaccination and the primary outcome of moderate-to-critical COVID-19 as well as maternal and perinatal outcomes were examined among all people who tested positive for SARS-CoV-2 between March and August 2020. The association between 2019 influenza vaccination and having a positive SARS-CoV-2 test was examined among a cohort of individuals who delivered on randomly selected dates between March and August 2020. Univariable and multivariable analyses were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 2325 people who tested positive for SARS-CoV-2, 1068 (45.9%) were vaccinated against influenza in 2019. Those who received the influenza vaccine were older, leaner, more likely to have private insurance, and identify as White or Hispanic. They were less likely to smoke tobacco and identify as Black. Overall, 419 (18.0%) had moderate, 193 (8.3%) severe, and 52 (2.2%) critical COVID-19. There was no association between influenza vaccination and moderate-to-critical COVID-19 (29.2% vs. 28.0%, adjusted OR 1.10, 95% CI 0.90–1.34) or adverse maternal and perinatal outcomes among those who tested positive. Of 8152 people who delivered in 2020, 4658 (57.1%) received the influenza vaccine. Prior vaccination was not associated with a difference in the odds of SARS-CoV-2 infection (3.8% vs. 4.2%, adjusted OR 0.94, 95% CI 0.74–1.19).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Prior influenza vaccination was not associated with decreased severity of COVID-19 or lower odds of SARS-CoV-2 infection in pregnancy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589378","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}
Chronic histiocytic intervillositis (CHI) is a rare inflammatory placental disease characterized by diffuse infiltration of monocytes into the intervillous space and is associated with adverse pregnancy outcomes. No treatment is currently validated and although in some small reports, steroids with hydroxychloroquine have been described. There are no data for other therapies in refractory cases.
Patients and Methods
We here report four cases of patients with a history of CHI treated with immunoglobulins during a subsequent pregnancy. The four patients with recurrent CHI had failed to previous immunomodulatory therapies with steroids and hydroxychloroquine. All patients had at least four pregnancy losses with histopathological confirmation of CHI for at least one pregnancy loss. The usual pregnancy-loss etiology screening and immunological screening were negative for all the patients.
Results
For three patients, intravenous immunoglobulins were initiated at the βHCG positivity at 1 g/kg every 15 days until delivery. In one case with combined therapy since the beginning of the pregnancy, intravenous immunoglobulins were introduced at 20 WG because of severe growth restriction. Two patients had live births at 36 WG and one patient at 39 WG. One patient, who presented early first-trimester hypertension and severe placental lesions, failed to intravenous immunoglobulins and had a pregnancy loss at 15 WG.
Conclusion
This is the first report demonstrating the potential benefit of intravenous immunoglobulins in recurrent chronic intervillositis. Larger studies are needed to confirm this potential benefit for patients presenting severe cases of recurrent CHI.
简介慢性组织细胞间质炎（CHI）是一种罕见的胎盘炎症性疾病，其特点是单核细胞弥漫性浸润到绒毛间隙，与不良妊娠结局有关。目前尚无有效的治疗方法，尽管在一些小的报告中，描述了使用羟氯喹的类固醇治疗。目前还没有针对难治性病例的其他疗法的数据：我们在此报告了四例曾有CHI病史的患者在随后的怀孕期间接受免疫球蛋白治疗的病例。这四例复发性CHI患者之前曾接受过类固醇和羟氯喹等免疫调节疗法，但均以失败告终。所有患者至少有四次妊娠失败，其中至少一次妊娠失败的组织病理学证实为CHI。所有患者的常规妊娠失败病因筛查和免疫学筛查结果均为阴性：3例患者在βHCG阳性时开始静脉注射免疫球蛋白，每15天1克/千克，直至分娩。一名患者从怀孕之初就开始接受联合治疗，由于生长发育严重受限，静脉注射免疫球蛋白的剂量为 20 WG。两名患者在 36 WG 和一名患者在 39 WG 时生下了活产婴儿。一名患者在妊娠初期出现高血压和严重的胎盘病变，静脉注射免疫球蛋白无效，在 15 WG 时妊娠失败：这是第一份证明静脉注射免疫球蛋白对复发性慢性间质性脉管炎有潜在益处的报告。需要进行更大规模的研究，以证实对复发性慢性间质性脊髓炎重症患者的潜在益处。
{"title":"Intravenous Immunoglobulins for Recurrent Chronic Histiocytic Intervillositis: A Series of Case Studies","authors":"Noémie Abisror, Meryam Cheloufi, Jonathan Cohen, Aurore Coulomb, Chloé McAvoy, Olivier Fain, Jean Luc Taupin, Vassilis Tsatsaris, Gilles Kayem, Arsène Mekinian","doi":"10.1111/aji.13898","DOIUrl":"10.1111/aji.13898","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Chronic histiocytic intervillositis (CHI) is a rare inflammatory placental disease characterized by diffuse infiltration of monocytes into the intervillous space and is associated with adverse pregnancy outcomes. No treatment is currently validated and although in some small reports, steroids with hydroxychloroquine have been described. There are no data for other therapies in refractory cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Methods</h3>\u0000 \u0000 <p>We here report four cases of patients with a history of CHI treated with immunoglobulins during a subsequent pregnancy. The four patients with recurrent CHI had failed to previous immunomodulatory therapies with steroids and hydroxychloroquine. All patients had at least four pregnancy losses with histopathological confirmation of CHI for at least one pregnancy loss. The usual pregnancy-loss etiology screening and immunological screening were negative for all the patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For three patients, intravenous immunoglobulins were initiated at the βHCG positivity at 1 g/kg every 15 days until delivery. In one case with combined therapy since the beginning of the pregnancy, intravenous immunoglobulins were introduced at 20 WG because of severe growth restriction. Two patients had live births at 36 WG and one patient at 39 WG. One patient, who presented early first-trimester hypertension and severe placental lesions, failed to intravenous immunoglobulins and had a pregnancy loss at 15 WG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This is the first report demonstrating the potential benefit of intravenous immunoglobulins in recurrent chronic intervillositis. Larger studies are needed to confirm this potential benefit for patients presenting severe cases of recurrent CHI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.13898","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554038","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}
Vulvovaginal candidiasis (VVC) is a common mucosal fungal infection, and Candida albicans is the main causative agent. The NLRP3 inflammasome plays an important role in VVC, but the underlying mechanism is unknown.
Method of Study
Vaginal epithelial cells were divided into three groups: control, C. albicans strain SC5314 (wild-type, WT), and WT+ Matt Cooper Compound 950 (MCC950, a specific NLRP3 inhibitor). After human vaginal epithelial cells were pretreated with 1 µmol/L MCC950 for 2 h, C. albicans (MOI = 1) was cocultured with the human vaginal epithelial cells for 12 h. The cell supernatants were collected, LDH was detected, and the IL-1β and IL-18 levels were determined by ELISA. The expression of the pyroptosis-related proteins NLRP3, Caspase-1 p20 and GSDMD was measured by Western blotting analysis. The protein expression of the pyroptosis-related N-terminus of GSDMD (GSDMD-N) was detected by immunofluorescence.
Results
In this study, we showed that the WT C. albicans strain induced pyroptosis in vaginal epithelial cells, as indicated by the LDH and proinflammatory cytokine levels and the upregulated levels of the pyroptosis-related proteins NLRP3, Caspase-1 p20, and GSDMD-N. MCC950 reversed the changes in the expression of these proteins and proinflammatory cytokines in vaginal epithelial cells.
Conclusion
C. albicans activated the NLRP3 inflammasome to induce vaginal epithelial cell pyroptosis. MCC950 inhibited the NLRP3 inflammasome, reduced vaginal epithelial cell pyroptosis, and decreased the release of inflammatory cytokines.
{"title":"Mechanism of Vaginal Epithelial Cell Pyroptosis Induced by the NLRP3 Inflammasome in Vulvovaginal Candidiasis","authors":"Yongmei Peng, Yanan Xu, Sainan Li, Mingkun Shao, Zijia Shen, Wenjin Qi","doi":"10.1111/aji.13893","DOIUrl":"10.1111/aji.13893","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Vulvovaginal candidiasis (VVC) is a common mucosal fungal infection, and <i>Candida albicans</i> is the main causative agent. The NLRP3 inflammasome plays an important role in VVC, but the underlying mechanism is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Vaginal epithelial cells were divided into three groups: control, <i>C. albicans</i> strain SC5314 (wild-type, WT), and WT+ Matt Cooper Compound 950 (MCC950, a specific NLRP3 inhibitor). After human vaginal epithelial cells were pretreated with 1 µmol/L MCC950 for 2 h, <i>C. albicans</i> (MOI = 1) was cocultured with the human vaginal epithelial cells for 12 h. The cell supernatants were collected, LDH was detected, and the IL-1β and IL-18 levels were determined by ELISA. The expression of the pyroptosis-related proteins NLRP3, Caspase-1 p20 and GSDMD was measured by Western blotting analysis. The protein expression of the pyroptosis-related N-terminus of GSDMD (GSDMD-N) was detected by immunofluorescence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this study, we showed that the WT <i>C. albicans</i> strain induced pyroptosis in vaginal epithelial cells, as indicated by the LDH and proinflammatory cytokine levels and the upregulated levels of the pyroptosis-related proteins NLRP3, Caspase-1 p20, and GSDMD-N. MCC950 reversed the changes in the expression of these proteins and proinflammatory cytokines in vaginal epithelial cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p><i>C. albicans</i> activated the NLRP3 inflammasome to induce vaginal epithelial cell pyroptosis. MCC950 inhibited the NLRP3 inflammasome, reduced vaginal epithelial cell pyroptosis, and decreased the release of inflammatory cytokines.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"92 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490592","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}
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