American Journal of Reproductive Immunology最新文献

{"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}

{"title":"Fecal CD200 as a Measure of Immunosuppressive CD200L and Proinflammatory CD200S at the Feto-Maternal Interface","authors":"David A. Clark,&nbsp;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⁺ 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.</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⁺ 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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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.</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}

{"title":"Polygonatum Odoratum (Mill.) Druce Alleviates Lipopolysaccharide-Induced Inflammation and Improves the Ovarian Function in Polycystic Ovary Syndrome Rats","authors":"Biao Zheng,&nbsp;Xuan Che,&nbsp;Zhuo Chen,&nbsp;Di Cheng,&nbsp;Congbing Huang,&nbsp;Zhaoming Zeng,&nbsp;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}

{"title":"Acute-Phase Proteins and Resistin in the Cervicovaginal Fluid of Women With Preterm Premature Rupture of Membranes","authors":"Hee Young Cho,&nbsp;Kyo Hoon Park,&nbsp;Min Jung Lee,&nbsp;Bo Young Choi,&nbsp;Da Eun Jeong,&nbsp;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> &lt; 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}

{"title":"Exploring Therapeutic Targets and Drugs for Recurrent Spontaneous Abortion by M1 Macrophage Exosome Sequencing Analysis: A Bioinformatic and Vitro Study","authors":"Cen Tang,&nbsp;Wanqin Hu,&nbsp;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}

{"title":"Gestational Aging on Fast Forward: The Epigenetic Link to Recurrent Pregnancy Loss","authors":"Anam Farooqui,&nbsp;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}

{"title":"Potential of Vaginal Microbiota Transplantation (VMT) in Endometritis Management","authors":"Masoud Lahouty,&nbsp;Morteza Abdi,&nbsp;Manouchehr Fadaee,&nbsp;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}

{"title":"Evaluating the Diagnostic Potential of Caveolin-1 in Fetal Growth Restriction: A Prospective Case–Control Study","authors":"Ruken Dayanan,&nbsp;Cemal Reşat Atalay","doi":"10.1111/aji.70111","DOIUrl":"https://doi.org/10.1111/aji.70111","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Fetal growth restriction (FGR) is a significant pregnancy complication associated with impaired placental angiogenesis and endothelial dysfunction, leading to adverse perinatal outcomes. Caveolin-1, a structural protein involved in vascular signaling, plays a critical role in regulating angiogenic factors such as VEGF, b-FGF, and eNOS. This study aimed to evaluate the diagnostic potential of serum caveolin-1 levels in FGR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>This prospective case–control study included 37 pregnant women diagnosed with FGR and 33 healthy controls matched for gestational age. Maternal serum caveolin-1 levels were measured using ELISA, and their association with clinical parameters, Doppler indices, and neonatal outcomes was analyzed. ROC analysis was performed to assess the diagnostic accuracy of caveolin-1 levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Maternal serum caveolin-1 levels were significantly reduced in the FGR group compared to controls (<i>p</i> = 0.011). Lower caveolin-1 levels in FGR were associated with higher Doppler indices (S/D, PI, RI) and adverse neonatal outcomes, including lower birth weights and Apgar scores. The ROC analysis demonstrated an AuROC of 0.677 with a cutoff value of &lt;222.37 pg/mL achieving a sensitivity of 60.6% and a specificity of 59.5%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Reduced serum caveolin-1 levels may be associated with impaired placental angiogenesis and adverse perinatal outcomes in FGR; however, further studies are needed to establish a definitive link. Caveolin-1 shows potential as a non-invasive biomarker for early detection and management of FGR. Further research is warranted to validate these findings and explore therapeutic implications.</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":"144273386","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}

{"title":"Prognostic Impact of Pregnancy-Associated Plasma Protein-A (PAPP-A) for Gestational Diabetes Mellitus (GDM): An Updated Systematic Review and Meta-Analysis of More Than 90 000 Pregnancies","authors":"Ing-Luen Shyu,&nbsp;Yung-Chieh Tsai,&nbsp;Tian-Ni Kuo,&nbsp;Yow-Ling Shiue","doi":"10.1111/aji.70087","DOIUrl":"https://doi.org/10.1111/aji.70087","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Gestational diabetes mellitus (GDM) constitutes a significant health concern during pregnancy, warranting a thorough investigation into potential prognostic markers. Pregnancy-associated plasma protein-A (PAPP-A), which is present at high levels during pregnancy, exhibits altered concentrations even before the clinical diagnosis of GDM, highlighting its potential as an early biomarker for this condition. This systematic review and meta-analysis aimed to review and synthesize the latest evidence comprehensively to explore the correlation between maternal PAPP-A levels and the development of GDM, drawing from the most recent publications available.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PubMed, EMBASE, and Cochrane CENTRAL were searched systematically up to June 2, 2024. Cohort and case-control studies reporting PAPP-A levels in GDM and non-GDM women with singleton pregnancy were eligible for inclusion. The quality of studies was measured using the Newcastle-Ottawa scale (NOS). Standardized mean differences (SMDs) of PAPP-A levels between GDM and non-GDM, and odds ratios (ORs) of the association between PAPP-A and GDM were pooled, with heterogeneity assessed using the Cochran Q test and <i>I</i>² statistic. Sensitivity analysis was employed (PROSPERO ID: CRD42024580169).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nineteen studies involving 92 200 pregnant women were included in the systematic review and meta-analysis. The gestational age at sampling varied from 10 to 14 weeks. Meta-analysis revealed a significantly lower PAPP-A level among women with GDM compared with those without (pooled SMD = −0.31, 95% CI: −0.56 to −0.06). Furthermore, meta-analysis revealed that women with a low PAPP-A level had a significantly higher risk of developing GDM (pooled OR = 1.75, 95% CI: 1.45–2.11). Despite observed publication bias, sensitivity analysis affirmed the robustness of the results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This updated systematic review and meta-analysis underscored the prognostic significance of maternal PAPP-A levels with respect to the development of GDM. Low PAPP-A level is associated with an increased risk of GDM. These findings advocate for the inclusion of PAPP-A assessment in the clinical evaluation of GDM risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220078","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}