Murat Levent Dereli, Sadun Sucu, Ahmet Kurt, Enes Kumcu, Emre Mat, Ali Turhan Çağlar
Objectives
To investigate the association between inflammatory indices derived from complete blood count (CBC) and delivery within 1 week for threatened preterm labor (tPTL) in order to contribute to the management algorithm for women with tPTL.
Materials and Methods
We conducted a retrospective cohort study of women with a singleton pregnancy and tPTL admitted to a large tertiary referral hospital between October 1, 2022, and May 31, 2023. After exclusion, the study groups were formed with 42 women who gave birth within 1 week of admission (group 1) and 84 women who gave birth later than 1 week after admission (group 2). The comparison focused mainly on whether there was a difference between the two groups in the systemic immune inflammation index (SII), systemic inflammatory response index (SIRI), and pan-immune inflammation value (PIV), as well as other inflammatory indices.
Results
Monocyte count, monocyte-to-lymphocyte ratio (MLR), SIRI, and PIV were significantly higher in group 1 (p = 0.038, 0.019, 0.029, and 0.037, respectively) and receiver operating characteristics curve analysis for discriminatory power to predict PTB within 1 week revealed area under the curve values of 0.613, 0.628, 0.620, and 0.614, respectively. The overall predictive power showed no significant superiority between the individual parameters.
Conclusions
Our preliminary results showed an association between increased inflammatory indices and an increased risk of delivery within 1 week in women with tPTL. In particular, SIRI and PIV with cut-off values of >4.3 × 103/µL and >677 × 106/µL2 respectively may facilitate decision-making in the management algorithm for women with tPTL. Further randomized controlled trials with a larger cohort are needed to better define efficacy and limitations.
{"title":"The Role of Blood Count-Derived Inflammatory Indices in the Short-Term Prediction of Delivery in Women With Threatened Preterm Labor","authors":"Murat Levent Dereli, Sadun Sucu, Ahmet Kurt, Enes Kumcu, Emre Mat, Ali Turhan Çağlar","doi":"10.1111/aji.70126","DOIUrl":"https://doi.org/10.1111/aji.70126","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To investigate the association between inflammatory indices derived from complete blood count (CBC) and delivery within 1 week for threatened preterm labor (tPTL) in order to contribute to the management algorithm for women with tPTL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We conducted a retrospective cohort study of women with a singleton pregnancy and tPTL admitted to a large tertiary referral hospital between October 1, 2022, and May 31, 2023. After exclusion, the study groups were formed with 42 women who gave birth within 1 week of admission (group 1) and 84 women who gave birth later than 1 week after admission (group 2). The comparison focused mainly on whether there was a difference between the two groups in the systemic immune inflammation index (SII), systemic inflammatory response index (SIRI), and pan-immune inflammation value (PIV), as well as other inflammatory indices.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Monocyte count, monocyte-to-lymphocyte ratio (MLR), SIRI, and PIV were significantly higher in group 1 (<i>p</i> = 0.038, 0.019, 0.029, and 0.037, respectively) and receiver operating characteristics curve analysis for discriminatory power to predict PTB within 1 week revealed area under the curve values of 0.613, 0.628, 0.620, and 0.614, respectively. The overall predictive power showed no significant superiority between the individual parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our preliminary results showed an association between increased inflammatory indices and an increased risk of delivery within 1 week in women with tPTL. In particular, SIRI and PIV with cut-off values of >4.3 × 10<sup>3</sup>/µL and >677 × 10<sup>6</sup>/µL<sup>2</sup> respectively may facilitate decision-making in the management algorithm for women with tPTL. Further randomized controlled trials with a larger cohort are needed to better define efficacy and limitations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573293","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}
Recurrent pregnancy loss (RPL) significantly affects reproductive health in couples of childbearing age. Its pathogenesis is complex, with nearly 50% of cases remaining unexplained, and immune regulation plays a key role in its development. This review focuses on the relationship between human microbiota (gut, reproductive tract, and endometrial microbiota), immune regulation, and RPL, systematically summarizing related research progress. RPL patients exhibit characteristic changes in the gut, reproductive tract, and endometrial microbiota, such as reduced gut microbial diversity, decreased beneficial bacteria, increased harmful bacteria in the reproductive tract, and an imbalanced endometrial microbiota structure. Dysbiosis can lead to immune regulation abnormalities, increasing the risk of RPL by disrupting immune tolerance, triggering inflammatory responses, and interfering with metabolism. Although microbiota-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, show potential, they face challenges related to strain selection, donor screening, and unclear mechanisms. Current research also faces limitations in detection technology and sample size, and the understanding of the microbiota-immune-RPL relationship requires further deepening. Future studies should clarify causal relationships using advanced technologies, develop more effective detection and intervention methods, and create personalized treatment plans based on individual patient characteristics to improve clinical diagnosis and treatment of RPL and safeguard women's reproductive health.
{"title":"The Impact of Microbiota-Mediated Immune Regulation on Recurrent Pregnancy Loss and Intervention Strategies","authors":"Yao Yao, Yiqing Ye, Caihong Zheng","doi":"10.1111/aji.70121","DOIUrl":"https://doi.org/10.1111/aji.70121","url":null,"abstract":"<div>\u0000 \u0000 <p>Recurrent pregnancy loss (RPL) significantly affects reproductive health in couples of childbearing age. Its pathogenesis is complex, with nearly 50% of cases remaining unexplained, and immune regulation plays a key role in its development. This review focuses on the relationship between human microbiota (gut, reproductive tract, and endometrial microbiota), immune regulation, and RPL, systematically summarizing related research progress. RPL patients exhibit characteristic changes in the gut, reproductive tract, and endometrial microbiota, such as reduced gut microbial diversity, decreased beneficial bacteria, increased harmful bacteria in the reproductive tract, and an imbalanced endometrial microbiota structure. Dysbiosis can lead to immune regulation abnormalities, increasing the risk of RPL by disrupting immune tolerance, triggering inflammatory responses, and interfering with metabolism. Although microbiota-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, show potential, they face challenges related to strain selection, donor screening, and unclear mechanisms. Current research also faces limitations in detection technology and sample size, and the understanding of the microbiota-immune-RPL relationship requires further deepening. Future studies should clarify causal relationships using advanced technologies, develop more effective detection and intervention methods, and create personalized treatment plans based on individual patient characteristics to improve clinical diagnosis and treatment of RPL and safeguard women's reproductive health.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550854","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}
Some studies have demonstrated that high level of natural killer (NK) cells or NK cytotoxicity was associated with unexplained recurrent pregnancy loss (RPL) and can serve as predictive indicator for subsequent miscarriage in RPL patients. This suggests that reducing the level or activity of NK cells may represent a potential therapeutic strategy. However, there remains controversy regarding the efficacy of current immunotherapies employed in clinical practice for modulating the number and function of NK cells in RPL patients. Consequently, this study aimed to systematically review and assess the impact of various immunotherapies on NK cells in RPL patients, as well as the effectiveness of improving pregnancy outcomes in RPL patients with abnormal NK cells level/activity. This systematic review and meta-analysis was conducted following the PRISMA guidelines and recommendations of the Cochrane Collaboration. A comprehensive search was conducted on PubMed, Web of Science, EMBASE, and the Cochrane Library to identify relevant studies on immunotherapy in patients with RPL up to September 2023. Meta-analyses were used to assess the impact of immunotherapy on NK cells level and activity in RPL patients. Narrative synthesis was conducted to evaluate the effect of immunotherapies on pregnancy outcomes in RPL patients with abnormal NK cells level/activity. Risk-of-bias was assessed using ROBINS-I. A random-effects model or a fixed-effects model was selected according to the heterogeneity test, and standard mean differences (SMDs), risk ratio (RR) and 95% confidence interval (95% CI) were calculated. A total of 17 studies were included in this analysis. The meta-analysis revealed that in the general population of patients with RPL, intravenous immunoglobulin (IVIg) led to a reduction in peripheral natural killer (pNK) cells level (SMD: −0.85, 95% CI: −1.41 to −0.28), lymphocyte immunotherapy (LIT) decreased pNK cell activity, and intralipid reduced both pNK cells level (SMD: −0.32, 95% CI: −0.64 to −0.01) and activity (SMD: −0.74, 95% CI: −1.06 to −0.42). The narrative synthesis illustrated the regulatory impact of immunotherapy on diverse immune cells and cytokines in RPL patients. Furthermore, IVIg and intralipid therapy could potentially enhance live birth rates in RPL patients specifically characterized by elevated pNK cells level. For RPL patients with elevated uterine NK (uNK) levels, cyclosporin A may ameliorate pregnancy outcomes, while prednisolone does not appear to have the same effect. Nevertheless, these findings should be approached with caution given the current insufficiency of evidence. Limited evidence indicated that IVIg, LIT, and intralipid reduce pNK cells level/activity in RPL patients. RPL patients with elevated NK levels may be benefit from immunotherapy, but not all immunotherapies were effective. However, interpretation of these results with caution is strongly advised due to the limited number of high-
{"title":"The Effect of Immunotherapy on Natural Killer Cells Level/Activity in Recurrent Pregnancy Loss (RPL) Patients: A Systematic Review and Meta-Analysis","authors":"Huan Xiao, Feng Zhang, Yulian Wu, Ruochun Lian, Lianghui Diao, Tailang Yin, Chunyu Huang","doi":"10.1111/aji.70118","DOIUrl":"https://doi.org/10.1111/aji.70118","url":null,"abstract":"<div>\u0000 \u0000 <p>Some studies have demonstrated that high level of natural killer (NK) cells or NK cytotoxicity was associated with unexplained recurrent pregnancy loss (RPL) and can serve as predictive indicator for subsequent miscarriage in RPL patients. This suggests that reducing the level or activity of NK cells may represent a potential therapeutic strategy. However, there remains controversy regarding the efficacy of current immunotherapies employed in clinical practice for modulating the number and function of NK cells in RPL patients. Consequently, this study aimed to systematically review and assess the impact of various immunotherapies on NK cells in RPL patients, as well as the effectiveness of improving pregnancy outcomes in RPL patients with abnormal NK cells level/activity. This systematic review and meta-analysis was conducted following the PRISMA guidelines and recommendations of the Cochrane Collaboration. A comprehensive search was conducted on PubMed, Web of Science, EMBASE, and the Cochrane Library to identify relevant studies on immunotherapy in patients with RPL up to September 2023. Meta-analyses were used to assess the impact of immunotherapy on NK cells level and activity in RPL patients. Narrative synthesis was conducted to evaluate the effect of immunotherapies on pregnancy outcomes in RPL patients with abnormal NK cells level/activity. Risk-of-bias was assessed using ROBINS-I. A random-effects model or a fixed-effects model was selected according to the heterogeneity test, and standard mean differences (SMDs), risk ratio (RR) and 95% confidence interval (95% CI) were calculated. A total of 17 studies were included in this analysis. The meta-analysis revealed that in the general population of patients with RPL, intravenous immunoglobulin (IVIg) led to a reduction in peripheral natural killer (pNK) cells level (SMD: −0.85, 95% CI: −1.41 to −0.28), lymphocyte immunotherapy (LIT) decreased pNK cell activity, and intralipid reduced both pNK cells level (SMD: −0.32, 95% CI: −0.64 to −0.01) and activity (SMD: −0.74, 95% CI: −1.06 to −0.42). The narrative synthesis illustrated the regulatory impact of immunotherapy on diverse immune cells and cytokines in RPL patients. Furthermore, IVIg and intralipid therapy could potentially enhance live birth rates in RPL patients specifically characterized by elevated pNK cells level. For RPL patients with elevated uterine NK (uNK) levels, cyclosporin A may ameliorate pregnancy outcomes, while prednisolone does not appear to have the same effect. Nevertheless, these findings should be approached with caution given the current insufficiency of evidence. Limited evidence indicated that IVIg, LIT, and intralipid reduce pNK cells level/activity in RPL patients. RPL patients with elevated NK levels may be benefit from immunotherapy, but not all immunotherapies were effective. However, interpretation of these results with caution is strongly advised due to the limited number of high-","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524987","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}
Patients with diarrhea-predominant irritable bowel syndrome have an increased risk of recurrent miscarriage (RM). Loss of chromosomally normal post-implantation embryos is triggered by the proinflammatory cytokines interferon-γ and TNF-α from NK cells and macrophages. Mouse models of RM similar to human unexplained RM have implicated fecal LPS as an important abortifacient. However, subnormal expression of immunosuppressive CD200L at the feto-maternal interface has also been implicated in RM. Human stool contains desquamated epithelium expressing immunosuppressive CD200L and stromal CD56+ NK cells releasing proinflammatory CD200S+ granules. We asked if subnormal epithelial CD200L was associated with increased degranulation of stromal CD200+CD56+NK cells. Systemic effects would include an augmented proinflammatory milieu at the feto-maternal decidual interface.
Methods of Study
Quantitative analysis of biopsies of proximal and distal colon for immunostained for CD200L, CD200S, and CD56-positive cells. CD200 ELISA Assay of stool extracts was done.
Results
Epithelium and underlying stroma showed CD200L+ cells, CD200S+ cells, and CD56+ cells releasing CD200S-positive granules. As epithelial CD200L expression decreased, the proportion of the degranulating CD56+ cells significantly increased. Degranulation was significantly greater in irritable bowel syndrome, diarrhea predominant subtype (IBS-D) cases compared to controls. CD200L was detected in stool extracts.
Conclusions
Decreased epithelial CD200L increased both CD66+ CD200S+ stromal cells and their degranulation. This implies potential functional effects. Stool CD200 may reflect the level of CD200 at the feto-maternal decidual interface.
{"title":"Fecal CD200 as a Measure of Immunosuppressive CD200L and Proinflammatory CD200S at the Feto-Maternal Interface","authors":"David A. Clark, Paul Moayyedi","doi":"10.1111/aji.70120","DOIUrl":"https://doi.org/10.1111/aji.70120","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Patients with diarrhea-predominant irritable bowel syndrome have an increased risk of recurrent miscarriage (RM). Loss of chromosomally normal post-implantation embryos is triggered by the proinflammatory cytokines interferon-γ and TNF-α from NK cells and macrophages. Mouse models of RM similar to human unexplained RM have implicated fecal LPS as an important abortifacient. However, subnormal expression of immunosuppressive CD200L at the feto-maternal interface has also been implicated in RM. Human stool contains desquamated epithelium expressing immunosuppressive CD200L and stromal CD56<sup>+</sup> NK cells releasing proinflammatory CD200S<sup>+</sup> granules. We asked if subnormal epithelial CD200L was associated with increased degranulation of stromal CD200<sup>+</sup>CD56<sup>+</sup>NK cells. Systemic effects would include an augmented proinflammatory milieu at the feto-maternal decidual interface.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods of Study</h3>\u0000 \u0000 <p>Quantitative analysis of biopsies of proximal and distal colon for immunostained for CD200L, CD200S, and CD56-positive cells. CD200 ELISA Assay of stool extracts was done.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Epithelium and underlying stroma showed CD200L<sup>+</sup> cells, CD200S<sup>+</sup> cells, and CD56<sup>+</sup> cells releasing CD200S-positive granules. As epithelial CD200L expression decreased, the proportion of the degranulating CD56<sup>+</sup> cells significantly increased. Degranulation was significantly greater in irritable bowel syndrome, diarrhea predominant subtype (IBS-D) cases compared to controls. CD200L was detected in stool extracts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Decreased epithelial CD200L increased both CD66<sup>+</sup> CD200S<sup>+</sup> stromal cells and their degranulation. This implies potential functional effects. Stool CD200 may reflect the level of CD200 at the feto-maternal decidual interface.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492600","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}
{"title":"Comment on—Intravenous Immunoglobulin Use in Patients With Unexplained Recurrent Pregnancy Loss","authors":"Yasemin Akgul Balaban","doi":"10.1111/aji.70119","DOIUrl":"https://doi.org/10.1111/aji.70119","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482235","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}
Biao Zheng, Xuan Che, Zhuo Chen, Di Cheng, Congbing Huang, Zhaoming Zeng, Zhongcheng Mo
Problem
Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligoovulation or anovulation, and the morphology of polycystic ovaries. Polygonatum odoratum (Mill.) Druce (POD), a key component of the traditional Chinese herb Polygonatum odoratum, has uncertain effects on improving ovarian function and inflammation in patients with PCOS.
Method of Study
Network pharmacological analysis was conducted to explore the processes and signaling pathways of POD in the treatment of PCOS. Letrozole via gavage induced the PCOS model rats. Ovarian morphology and the ovarian body index were assessed, and the numbers of corpora lutea and cystic follicles were quantified after hematoxylin‒eosin staining. Testosterone and fasting blood glucose levels were measured, and glucose tolerance was evaluated. Additionally, IL-1β and TNF-αlevels in the ovaries were detected using immunohistochemistry and western blotting.
Results
Network pharmacology identified a total of 107 potential targets associated with POD and PCOS, suggested that POD could treat PCOS through mechanisms involving inflammation, the response to LPS, metabolic pathways. Experiments demonstrated that LPS reduced the number of corpora lutea and increased the number of cystic follicles while also impairing glucose regulation in PCOS rats. Moreover, LPS increased the expression levels of IL-1β and TNF-α. Treatment with POD mitigated these changes.
Conclusions
Our findings indicate that LPS exacerbates ovarian dysfunction and inflammation in PCOS rats, while POD effectively reverses these changes, suggesting a promising avenue for research into the therapeutic potential of traditional Chinese medicine in the treatment of PCOS.
{"title":"Polygonatum Odoratum (Mill.) Druce Alleviates Lipopolysaccharide-Induced Inflammation and Improves the Ovarian Function in Polycystic Ovary Syndrome Rats","authors":"Biao Zheng, Xuan Che, Zhuo Chen, Di Cheng, Congbing Huang, Zhaoming Zeng, Zhongcheng Mo","doi":"10.1111/aji.70116","DOIUrl":"https://doi.org/10.1111/aji.70116","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligoovulation or anovulation, and the morphology of polycystic ovaries. Polygonatum odoratum (Mill.) Druce (POD), a key component of the traditional Chinese herb Polygonatum odoratum, has uncertain effects on improving ovarian function and inflammation in patients with PCOS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Network pharmacological analysis was conducted to explore the processes and signaling pathways of POD in the treatment of PCOS. Letrozole via gavage induced the PCOS model rats. Ovarian morphology and the ovarian body index were assessed, and the numbers of corpora lutea and cystic follicles were quantified after hematoxylin‒eosin staining. Testosterone and fasting blood glucose levels were measured, and glucose tolerance was evaluated. Additionally, IL-1β and TNF-αlevels in the ovaries were detected using immunohistochemistry and western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Network pharmacology identified a total of 107 potential targets associated with POD and PCOS, suggested that POD could treat PCOS through mechanisms involving inflammation, the response to LPS, metabolic pathways. Experiments demonstrated that LPS reduced the number of corpora lutea and increased the number of cystic follicles while also impairing glucose regulation in PCOS rats. Moreover, LPS increased the expression levels of IL-1β and TNF-α. Treatment with POD mitigated these changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings indicate that LPS exacerbates ovarian dysfunction and inflammation in PCOS rats, while POD effectively reverses these changes, suggesting a promising avenue for research into the therapeutic potential of traditional Chinese medicine in the treatment of PCOS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367436","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}
Hee Young Cho, Kyo Hoon Park, Min Jung Lee, Bo Young Choi, Da Eun Jeong, Eun Mi Im
Problem
To determine whether altered cervicovaginal fluid (CVF) levels of acute-phase proteins (APPs) and resistin, alone or in combination with conventional clinical and blood-based markers, could predict microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI) and acute histologic chorioamnionitis (HCA) in women with preterm premature rupture of membranes (PPROM).
Methods of study
Women with singleton pregnancies with PPROM at 20 + 0–34 + 0 weeks (n = 82) were retrospectively evaluated. Amniotic fluid (AF) obtained via amniocentesis was cultured to diagnose MIAC, and interleukin-6 levels (≥ 2.6 ng/mL) were used to diagnose IAI. Haptoglobin, MBL, pentraxin-2, RBP4, serpin A1, and resistin levels in CVF samples, collected during amniocentesis, were determined by ELISA. Neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein levels were measured.
Results
The prevalence of MIAC and/or IAI and acute HCA was 53.6% (44/82) and 49.3% (38/77), respectively. Multivariate logistic regression analyses revealed that (i) elevated CVF haptoglobin (adjusted odds ratio [aOR], 5.857; 95% confidence interval [CI], 1.263–27.173), pentraxin-2 (aOR, 1.024; 95% CI, 1.005–1.043), and resistin (aOR, 1.009; 95% CI, 1.003–1.015) levels were independently associated with MIAC/IAI, and (ii) elevated CVF resistin levels (aOR, 1.009; 95% CI, 1.003–1.015) were independently associated with acute HCA after adjusting for baseline covariates. Using stepwise regression analysis, a noninvasive prediction model comprising CVF, resistin, and pentraxin-2 levels, NLR, and gestational age at sampling was developed, which provided a good prediction of MIAC/IAI (area under the curve [AUC], 0.87; 95% CI, 0.78–0.95), with greater predictive potential than any single covariate included in the model (resistin: AUC, 0.72; 95% CI, 0.60-0.83; pentraxin-2: AUC, 0.64; 95% CI, 0.52-0.76; NLR: AUC, 0.74; 95% CI, 0.62-0.85; gestational age: AUC, 0.71; 95% CI, 0.60–0.82) (p < 0.05 for each).
Conclusions
Haptoglobin, pentraxin-2, and resistin levels in the CVF may be valuable to evaluate the risk of MIAC, IAI, and acute HCA in women with PPROM. In particular, the combination of these acute-phase and inflammatory CVF biomarkers with conventional clinical and blood-based markers can significantly support MIAC/IAI diagnosis.
{"title":"Acute-Phase Proteins and Resistin in the Cervicovaginal Fluid of Women With Preterm Premature Rupture of Membranes","authors":"Hee Young Cho, Kyo Hoon Park, Min Jung Lee, Bo Young Choi, Da Eun Jeong, Eun Mi Im","doi":"10.1111/aji.70117","DOIUrl":"https://doi.org/10.1111/aji.70117","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>To determine whether altered cervicovaginal fluid (CVF) levels of acute-phase proteins (APPs) and resistin, alone or in combination with conventional clinical and blood-based markers, could predict microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI) and acute histologic chorioamnionitis (HCA) in women with preterm premature rupture of membranes (PPROM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods of study</h3>\u0000 \u0000 <p>Women with singleton pregnancies with PPROM at 20 + 0–34 + 0 weeks (<i>n</i> = 82) were retrospectively evaluated. Amniotic fluid (AF) obtained via amniocentesis was cultured to diagnose MIAC, and interleukin-6 levels (≥ 2.6 ng/mL) were used to diagnose IAI. Haptoglobin, MBL, pentraxin-2, RBP4, serpin A1, and resistin levels in CVF samples, collected during amniocentesis, were determined by ELISA. Neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein levels were measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The prevalence of MIAC and/or IAI and acute HCA was 53.6% (44/82) and 49.3% (38/77), respectively. Multivariate logistic regression analyses revealed that (i) elevated CVF haptoglobin (adjusted odds ratio [aOR], 5.857; 95% confidence interval [CI], 1.263–27.173), pentraxin-2 (aOR, 1.024; 95% CI, 1.005–1.043), and resistin (aOR, 1.009; 95% CI, 1.003–1.015) levels were independently associated with MIAC/IAI, and (ii) elevated CVF resistin levels (aOR, 1.009; 95% CI, 1.003–1.015) were independently associated with acute HCA after adjusting for baseline covariates. Using stepwise regression analysis, a noninvasive prediction model comprising CVF, resistin, and pentraxin-2 levels, NLR, and gestational age at sampling was developed, which provided a good prediction of MIAC/IAI (area under the curve [AUC], 0.87; 95% CI, 0.78–0.95), with greater predictive potential than any single covariate included in the model (resistin: AUC, 0.72; 95% CI, 0.60-0.83; pentraxin-2: AUC, 0.64; 95% CI, 0.52-0.76; NLR: AUC, 0.74; 95% CI, 0.62-0.85; gestational age: AUC, 0.71; 95% CI, 0.60–0.82) (<i>p</i> < 0.05 for each).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Haptoglobin, pentraxin-2, and resistin levels in the CVF may be valuable to evaluate the risk of MIAC, IAI, and acute HCA in women with PPROM. In particular, the combination of these acute-phase and inflammatory CVF biomarkers with conventional clinical and blood-based markers can significantly support MIAC/IAI diagnosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323670","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}
Recurrent spontaneous abortion (RSA) is defined as two or more consecutive spontaneous abortions in the first 24 weeks of pregnancy. However, the detailed molecular mechanisms behind RSA remain unclear.
Method of Study
We used bioinformatics and systems biology approaches to analyze the underlying molecular mechanisms to provide new insights into the biology of M1 macrophage exosome differentially expressed genes (DEGs) in RSA patients and to identify potential drugs to treat RSA. The trophoblast (HTR-8) was co-cultured with the M1 macrophage exosomes induced by THP-1, and the cell model was constructed for transcriptome sequencing analysis and data source construction. Functional enrichment and pathway analysis of DEGs among the three groups were performed. In addition, differential expression of key genes was verified by RT-qPCR.
Results
We obtained 172 DEGs from the sequencing data. Metabolic and immune-related pathways and functions are the main pathways of its enrichment. FOCX1, GATA2, YY1, TFAP2A, MEFF2A, and STAT3 are the major transcription factors (TFs) of M1 macrophage exosomes in RSA. Hsa-mir-106b-5p, hsa-mir-149-3p, and hsa-mir-520a-3p are associated with RSA. Finally, the DEGS-disease and DEGS-drug interaction networks are predicted. Gene Ontology (GO) and Kyoto Genome Encyclopedia (KEGG) enrichment analysis revealed clusters and targets associated with maternal and fetal interface immune tolerance in RSA M1 macrophage exosomes.
Conclusions
The candidate targets and drugs obtained from M1-type macrophage exosomes in this study may contribute to the effective treatment of RSA.
{"title":"Exploring Therapeutic Targets and Drugs for Recurrent Spontaneous Abortion by M1 Macrophage Exosome Sequencing Analysis: A Bioinformatic and Vitro Study","authors":"Cen Tang, Wanqin Hu, Yunhua Liu","doi":"10.1111/aji.70115","DOIUrl":"https://doi.org/10.1111/aji.70115","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Recurrent spontaneous abortion (RSA) is defined as two or more consecutive spontaneous abortions in the first 24 weeks of pregnancy. However, the detailed molecular mechanisms behind RSA remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>We used bioinformatics and systems biology approaches to analyze the underlying molecular mechanisms to provide new insights into the biology of M1 macrophage exosome differentially expressed genes (DEGs) in RSA patients and to identify potential drugs to treat RSA. The trophoblast (HTR-8) was co-cultured with the M1 macrophage exosomes induced by THP-1, and the cell model was constructed for transcriptome sequencing analysis and data source construction. Functional enrichment and pathway analysis of DEGs among the three groups were performed. In addition, differential expression of key genes was verified by RT-qPCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We obtained 172 DEGs from the sequencing data. Metabolic and immune-related pathways and functions are the main pathways of its enrichment. FOCX1, GATA2, YY1, TFAP2A, MEFF2A, and STAT3 are the major transcription factors (TFs) of M1 macrophage exosomes in RSA. Hsa-mir-106b-5p, hsa-mir-149-3p, and hsa-mir-520a-3p are associated with RSA. Finally, the DEGS-disease and DEGS-drug interaction networks are predicted. Gene Ontology (GO) and Kyoto Genome Encyclopedia (KEGG) enrichment analysis revealed clusters and targets associated with maternal and fetal interface immune tolerance in RSA M1 macrophage exosomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The candidate targets and drugs obtained from M1-type macrophage exosomes in this study may contribute to the effective treatment of RSA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323561","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}
Recurrent pregnancy loss (RPL) is a distressing complication with poorly understood causes. Increasing evidence suggests that epigenetic mechanisms, including those governing gestational age (GA), play a critical role in feto–maternal interactions and may contribute to pregnancy loss. Understanding these epigenetic alterations could provide new avenues for the prevention and management of RPL.
Method
We analyzed DNA methylation data from chorionic villi to evaluate epigenetic gestational age (EGA) in RPL cases. Using the Mayne clock, we compared EGA with clinical GA. Furthermore, weighted gene co-methylation network analysis (WGCNA) was applied to assess correlations between EGA and RPL and to identify gene modules linked to key biological pathways.
Results
RPL samples exhibited significantly higher EGA than their clinical GA, indicating accelerated placental aging. Control samples showed close alignment between EGA and clinical GA. WGCNA revealed a strong positive correlation between elevated EGA and RPL, and identified modules associated with critical pathways.
Conclusion
Our findings suggest that premature epigenetic aging of the placenta and disrupted networks regulating apoptosis, DNA repair, oxidative stress, and immune responses may underlie RPL. These insights highlight the importance of epigenetic regulation in pregnancy outcomes and warrant further investigation.
{"title":"Gestational Aging on Fast Forward: The Epigenetic Link to Recurrent Pregnancy Loss","authors":"Anam Farooqui, Susan Idicula-Thomas","doi":"10.1111/aji.70114","DOIUrl":"https://doi.org/10.1111/aji.70114","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Recurrent pregnancy loss (RPL) is a distressing complication with poorly understood causes. Increasing evidence suggests that epigenetic mechanisms, including those governing gestational age (GA), play a critical role in feto–maternal interactions and may contribute to pregnancy loss. Understanding these epigenetic alterations could provide new avenues for the prevention and management of RPL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We analyzed DNA methylation data from chorionic villi to evaluate epigenetic gestational age (EGA) in RPL cases. Using the Mayne clock, we compared EGA with clinical GA. Furthermore, weighted gene co-methylation network analysis (WGCNA) was applied to assess correlations between EGA and RPL and to identify gene modules linked to key biological pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>RPL samples exhibited significantly higher EGA than their clinical GA, indicating accelerated placental aging. Control samples showed close alignment between EGA and clinical GA. WGCNA revealed a strong positive correlation between elevated EGA and RPL, and identified modules associated with critical pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that premature epigenetic aging of the placenta and disrupted networks regulating apoptosis, DNA repair, oxidative stress, and immune responses may underlie RPL. These insights highlight the importance of epigenetic regulation in pregnancy outcomes and warrant further investigation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323560","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}
Endometritis is an inflammatory disorder often associated with microbial imbalance. Common treatments, such as antibiotics, may lead to drug resistance and do not ensure long-term microbial stability.
Method of Study
This mini review examines vaginal microbiota transplantation (VMT) as a novel approach to the management of endometritis. VMT involves the transfer of healthy microbiota from a donor to restore microbial balance in the recipient.
Results
VMT helps maintain vaginal acidity and inhibit pathogenic bacteria by restoring the dominant Lactobacillus spp. One of its key mechanisms is inhibiting the NF-κB signaling pathway, which leads to a decrease in inflammatory cytokines such as IL-6, IL-1β, and TNF-α. This reduces tissue inflammation and improves healing. VMT is also more biocompatible than antibiotics and can be more effective in combination with other treatments.
Conclusions
VMT is a promising noninvasive approach to the treatment of endometritis, with safety and microbial benefits. However, further studies and standardization of methods are needed to confirm its clinical utility.
{"title":"Potential of Vaginal Microbiota Transplantation (VMT) in Endometritis Management","authors":"Masoud Lahouty, Morteza Abdi, Manouchehr Fadaee, Javad Nezhadi","doi":"10.1111/aji.70104","DOIUrl":"https://doi.org/10.1111/aji.70104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Endometritis is an inflammatory disorder often associated with microbial imbalance. Common treatments, such as antibiotics, may lead to drug resistance and do not ensure long-term microbial stability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>This mini review examines vaginal microbiota transplantation (VMT) as a novel approach to the management of endometritis. VMT involves the transfer of healthy microbiota from a donor to restore microbial balance in the recipient.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>VMT helps maintain vaginal acidity and inhibit pathogenic bacteria by restoring the dominant Lactobacillus spp. One of its key mechanisms is inhibiting the NF-κB signaling pathway, which leads to a decrease in inflammatory cytokines such as IL-6, IL-1β, and TNF-α. This reduces tissue inflammation and improves healing. VMT is also more biocompatible than antibiotics and can be more effective in combination with other treatments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>VMT is a promising noninvasive approach to the treatment of endometritis, with safety and microbial benefits. However, further studies and standardization of methods are needed to confirm its clinical utility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273385","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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