American Journal of Reproductive Immunology最新文献

{"title":"SMURF2 Inhibits Autophagy and Growth in Ovarian Cancer by Regulating the RACK1/AKT/mTOR Pathway","authors":"Lei Wu,&nbsp;Ziyi Xiao,&nbsp;Siyue Zhang,&nbsp;Li Guo,&nbsp;Xiaojian Liu,&nbsp;Lihua Zhang,&nbsp;Jingjing Xu,&nbsp;Mengmeng Lv,&nbsp;Jinhua Wang","doi":"10.1111/aji.70140","DOIUrl":"https://doi.org/10.1111/aji.70140","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ovarian cancer (OC) is a common malignancy characterized by disseminated peritoneal metastases. Smad ubiquitin regulatory factor 2 (SMURF2) is involved in OC progression by stabilizing receptor for activated C kinase 1 (RACK1). However, the functions and mechanisms of action of SMURF2 in OC remain unclear. This biological function of SMURF2 in OC and its potential mechanisms of action were investigated in this study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The expression of SMURF2 in ovarian tumor tissues, patient serum, and OC cell lines was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and/or western blotting. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays, flow cytometry, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) were used for detecting cell proliferation and apoptosis. Autophagosomes in SKOV3 cells were observed using transmission electron microscopy. Immunohistochemistry and RT-qPCR were performed to evaluate SMURF2 expression. The levels of proteins related to autophagy and RACK1 were measured using western blotting and RT-qPCR, respectively. Western blotting was performed to assess the expression of AKT/mTOR pathway-related proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SMURF2 was underexpressed in OC tissues and cell lines compared with that in adjacent normal tissues or normal ovarian epithelial cells. RT-qPCR results suggested that SMURF2 was downregulated in the serum of patients with OC. SMURF2 overexpression inhibited SKOV3 cell growth and autophagy, and induced apoptosis both in vitro and in vivo. Moreover, SMURF2 overexpression suppressed RACK1 expression in SKOV3 cells. The AKT/mTOR pathway was activated by SMURF2 overexpression in SKOV3, and OC cells and tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SMURF2 plays a key role in OC by inhibiting cell autophagy and growth via activation of the RACK1/AKT/mTOR pathway, which might potentially be a new biomarker for OC diagnosis and therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861710","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":"ATP/P2X4 Regulates Inflammation and Oxidative Stress in Endometriosis Through NLRP3 Inflammasome–Dependent Mechanisms","authors":"Tingting Wu,&nbsp;Yan Guo","doi":"10.1111/aji.70132","DOIUrl":"https://doi.org/10.1111/aji.70132","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Endometriosis (EMS) is a chronic inflammatory disorder with ectopic endometrial tissues arising in extrauterine areas. We investigated the mechanism of adenosine triphosphate (ATP)/P2X4 regulating inflammation and oxidative stress in EMS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Normal endometrial tissues and ectopic endometrial tissues were collected, and determined for P2X4 expression by immunohistochemical staining. Normal (nESCs) and ectopic endometrial stromal cells (eESCs) were isolated and manipulated with Apyrase (a soluble ATP-diphosphohydrolase), 5-BDBD (a P2X4 receptor antagonist), or Nigericin (a NOD-like receptor 3 [NLRP3] inflammasome activator). The ATP concentration in endometrial tissues and cells were assessed through the ATP colorimetric/fluorescence assay, and cellular P2X4 expression was determined by RT-qPCR. Fluo 3-AM calcium ion fluorescence probe was utilized for detecting calcium ion concentration. Levels of inflammation-associated proteins (interleukin [IL]-1β, tumor necrosis factor-alpha [TNF-α], IL-6, IL-18), oxidative stress indicators (malondialdehyde [MDA], superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GSH-Px]), reactive oxygen species (ROS), and the NLRP3 inflammasome pathway-related proteins were determined by ELISA, DCFH-DA fluorescent probe, and Western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ATP and P2X4 were upregulated in EMS. Apyrase or 5-BDBD treatment or P2X4 knockdown reduced the concentration of Ca²⁺ and levels of IL-1β, TNF-α, IL-6, MDA, and ROS, but increased the activities of SOD, GSH-Px, and CAT in eESCs. Besides, 5-BDBD treatment decreased the expression levels of the NLRP3 inflammasome pathway-related proteins in eESCs and suppressed the secretion of IL-1β and IL-18. Nigericin could reverse the inhibitory impact of 5-BDBD on NLRP3 inflammasome activation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Altogether, ATP/P2X4 aggravates inflammation and oxidative stress in EMS by activating NLRP3.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843448","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":"Down-Regulation of Klotho/FGF23 by Low-Expressed VEGFR2 Inhibits the GH/IGF-1/PI3K/AKT Signaling Pathway Inducing Intrauterine Growth Restriction in Rats","authors":"Li Zhang,&nbsp;Linlu Zheng,&nbsp;Yaying Cheng","doi":"10.1111/aji.70110","DOIUrl":"https://doi.org/10.1111/aji.70110","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Intrauterine growth restriction (IUGR) is a pregnancy complication characterized by failure of the fetus to reach its genetic growth potential. We established the association <i>Klotho</i>, <i>fibroblast growth factor 23</i> (<i>FGF23</i>), and <i>vascular endothelial growth factor receptor 2</i> (<i>VEGFR2</i>) with IUGR for the first time, hoping to provide new insights for its diagnosis and treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>Sixteen pregnant rats were randomly divided into a low-protein diet group (IUGR group) and a control group. Placental tissues were sampled to detect <i>Klotho</i>, <i>FGF23</i>, <i>VEGFR2</i> mRNA, and protein expression in placental tissues of pregnant rats using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Bioinformatics methods were also used to predict the signaling pathways involved in <i>Klotho</i>, <i>FGF23</i>, and <i>VEGFR2</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The weight and crown-rump length of fetal rats in the IUGR group were significantly lower than those in the control group (<i>p </i>&lt; 0.05). The expression levels of <i>Klotho</i>, <i>FGF23</i>, and <i>VEGFR2</i> in IUGR group placental tissues were significantly lower than those in the control group (<i>p </i>&lt; 0.05). Meanwhile, based on bioinformatics, it was predicted that <i>VEGFR2</i> might affect the activation of the PI3K/AKT signaling pathway by growth hormone (GH)/insulin-like growth factor-1(IGF-1) through <i>Klotho</i>/<i>FGF23</i> axis inhibition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>IUGR caused by a low protein diet reduced birth weight and crown-rump length and low expression of <i>Klotho</i>, <i>FGF23</i>, and <i>VEGFR2</i> in placental tissues, which may inhibit fetal growth through the <i>VEGFR2-Klotho-FGF23-</i>GH-IGF-1-PI3K-AKT signaling axis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832540","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":"Identification of Immunophenotypes as a Mediator of Gut Microbiota-Driven Female Anovulation-Induced Infertility: A Mediation Mendelian Randomization Study","authors":"Xiyin Wang,&nbsp;Jing Zhang,&nbsp;Xianyuan Yi,&nbsp;Duozhen Chen","doi":"10.1111/aji.70135","DOIUrl":"https://doi.org/10.1111/aji.70135","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The mediatory roles of immune cells in the gut microbiota and anovulation-induced infertility remain unclear. This study aimed to investigate the correlations among gut microbiota, immunophenotypes, and anovulation-induced female infertility using a mediation Mendelian randomization (MR) study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An MR design investigates the causal links among gut microbiota (<i>n</i> = 14 306, 195 bacterial taxa), 731 immunophenotypes, and anovulation-induced female infertility (5667 anovulation-induced infertile women and 117 098 controls). The causal effects were evaluated by MR Egger, weighted median, inverse variance weighted (IVW), simple mode method, and weighted mode.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two phylum members (Cyanobacteria and Bacteroidetes), an order member (Burkholderiales), a family member (Defluviitaleaceae), and seven genus members were causally correlated with the anovulation-induced infertility. Among the seven genera, <i>Subdoligranulum</i>, <i>Clostridium innocuum</i> group, and <i>Escherichia.Shigella</i> were the risk factors, and <i>Prevotella9</i>, <i>Ruminococcus torques</i> group, <i>Eubacterium ventriosum</i> group, and <i>Eubacterium fissicatena</i> group were the protective factors in anovulation-induced infertility. Next, 35 immunophenotypes were identified to be also causally correlated with the anovulation-induced infertility. Among them, 15 immunophenotypes were significantly driven by the seven-microbiota genus and might be the internal mediating mechanism of the influence of gut microbiota on anovulation-induced female infertility. In the mediated MR analysis, four (<i>Clostridium innocuum</i> group, <i>Eubacterium fissicatena</i> group, <i>Eubacterium ventriosum</i> group, and <i>Prevotella9</i>) of the microbiota were directly influenced by six immunophenotypes (T cell, B cell, and dendritic cell panels) and then affected the anovulation-induced infertility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The mediation MR study provides evidence supporting immunophenotypes as mediators of gut microbiota-influenced female infertility, especially anovulation-induced infertility.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144809191","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":"Revisiting the Link Between Factor XII and Recurrent Pregnancy Loss: A Scoping Review","authors":"Emma Bundgaard,&nbsp;Malene Kræpping Pedersen,&nbsp;Pinar Bor,&nbsp;Mustafa Vakur Bor","doi":"10.1111/aji.70127","DOIUrl":"https://doi.org/10.1111/aji.70127","url":null,"abstract":"<p>Pregnancy loss affects approximately 23% of women, with 1%–3% experiencing recurrent pregnancy loss (RPL), defined as two or more consecutive miscarriages. Despite extensive research, up to 50% of RPL cases remain unexplained, making it a complex issue in reproductive medicine. Coagulation Factor XII (FXII) a key component of the contact activation pathway, has been suggested to play a role in RPL. Low FXII levels may lead to placental dysfunction and hypercoagulability, increasing the risk of adverse pregnancy outcomes, including RPL. This scoping review aimed to evaluate the association between FXII levels and RPL. Literature was retrieved from the PubMed database and EMBASE by a systematic search. A total of 218 studies were identified, of which 12 met the inclusion criteria published between 1992 and 2015, encompassing a total of 2362 RPL patients. They investigated FXII activity (<i>n</i> = 7), the C46T polymorphism (<i>n</i> = 3), or autoantibodies to FXII (<i>n</i> = 2) association to RPL. Available evidence suggests a potential association between low FXII levels, FXII antibodies, and RPL, probably via a prothrombotic mechanism as indicated by studies conducted 10–30 years ago. This highlights the need for further and more recent research to better elucidate the role of FXII in reproductive health and pregnancy outcomes.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767355","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":"Emerging Mechanisms of NK Cell Dysfunction in Endometriosis: The Role of Autophagy, Metabolism, Cytokines, Exosomes, and Trogocytosis","authors":"Mohammad Abbaszadeh,&nbsp;Mojdeh Soltani,&nbsp;Sara Falahi,&nbsp;Nafiseh Esmaeil","doi":"10.1111/aji.70138","DOIUrl":"https://doi.org/10.1111/aji.70138","url":null,"abstract":"<div>\u0000 \u0000 <p>Endometriosis (EMS) is a persistent, inflammatory condition that relies on estrogen and is distinguished by the proliferation of endometrial tissue outside the confines of the uterus. The impact on the well-being of individuals affected can be significant, as it is linked to pelvic pain and reduced fertility in women of reproductive age. Over 30 years have passed since initially discovering a malfunction in the activity of natural killer (NK) cells in individuals with EMS. Several aspects that contribute to NK cell dysfunction have been explored by researchers over the years, such as the upregulation of inhibitory receptors, downregulation of activating receptors, and the exhaustion process. Nonetheless, there are still many aspects that have yet to be identified. The objective of this review is to explore whether there is a connection between mechanisms that have not yet been explored and the malfunctioning of EMS-derived NK cells. Autophagy, metabolism, trogocytosis, tunneling nanotubes (TNT), and exosomes are among the factors that play a role in these processes. The primary objective of this publication is to provide valuable insights for future research on NK cells, with the aim of enhancing our understanding of the disease's causes and identifying more effective targets for immunotherapy.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773593","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":"Cognitive Dysfunction in Systemic Lupus Erythematosus During Pregnancy.","authors":"Philippe Leff, Daniela Chinchilla-Ochoa, Efraín Olivas-Peña, Martha Lucía Granados-Cepeda, Karla Cristina Trejo-Sánchez, Blanca Eugenia Farfán-Labonne","doi":"10.1111/aji.70134","DOIUrl":"https://doi.org/10.1111/aji.70134","url":null,"abstract":"<p><strong>Problem: </strong>Systemic lupus erythematosus (SLE) is characterized by an abnormal immune response, leading to elevated levels of autoantibodies that may distress the hepatic, renal, and central nervous systems. Cognitive dysfunction (CD) is the second most common neuropsychiatric symptom reported in SLE patients, after headache. CD has been linked to increased liver serum markers and kidney dysfunction in SLE patients. However, CD has not been previously described in pregnant women with SLE, although it can significantly impact decision-making and quality of life during pregnancy. Our primary goal was to assess the prevalence of CD in pregnant women with quiescent SLE (QSLE). Additionally, we aimed to describe the correlation between CD and serum levels of autoantibodies, complement system components, and hepatic and renal serology.</p><p><strong>Method of study: </strong>We conducted a cross-section study involving QSLE pregnant women (n = 63) and healthy pregnant controls (n = 52) in their third trimester. CD was assessed using the MoCA test. Biochemical determinations were performed by ELISA, and clinical data for creatinine and urea were also analyzed.</p><p><strong>Results: </strong>Higher CD rates were observed in QSLE pregnant women (30.16 %, QSLE CD(+)) compared to the healthy group (5.7%, CTR CD(+)). Serum levels of liver (ALT: QSLE CD(+) 65.9 ± 26.5 vs. QSLE CD(-) 39.9 ± 14.6, p = 0.00) and renal markers (urea: QSLE CD(+) 6.27 ± 2.1 vs. QSLE CD(-) 3.3 ± 1.1, p = 0.00) were significantly elevated in QSLE CD(+) pregnant women. AST and ALT showed a significant correlation with the MoCA score for QSLE CD(+) patients.</p><p><strong>Conclusions: </strong>MoCA total score, as well as attention, visuospatial/executive, and abstraction domains were found to be impaired in QSLE CD(+) pregnant patients. Subclinical liver and kidney dysfunction were associated with cognitive impairment in QSLE pregnant women.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 2","pages":"e70134"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803205","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":"Mendelian Randomization Study of Sex Hormone Binding Globulin and Its Influence on Adverse Pregnancy Outcomes.","authors":"Han Wu, Yiying Jin, Qiuhui Pan, Feng Cheng, Chaoyan Yue","doi":"10.1111/aji.70139","DOIUrl":"https://doi.org/10.1111/aji.70139","url":null,"abstract":"<p><strong>Background: </strong>The relationship between sex hormone-binding globulin (SHBG) levels and the risk of adverse pregnancy outcomes (APOs) remains controversial. A two-sample Mendelian randomization (MR) study was performed to clarify the causality of SHBG on the risk of APO.</p><p><strong>Methods: </strong>Significant single-nucleotide polymorphisms (SNPs) associated with SHBG levels were obtained from the genome-wide association study (GWAS) in the European population. Summary statistics of the number of spontaneous miscarriages, preeclampsia, gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP), and female infertility were utilized as the outcome. The causality was examined primarily by inverse-variance weighted (IVW), along with MR-Egger regression, weighted median estimator, and weighted mode method.</p><p><strong>Results: </strong>Based on the IVW model, every genetically predicted standard deviation (SD) increase in SHBG levels was causally associated with 0.023 SDs decrease of the number of spontaneous miscarriages (Beta ± SE: -0.023 ± 0.010, p = 0.018), 11.3% decrease of the risk of preeclampsia (OR = 0.887, 95% CI: 0.806-0.977, p = 0.015), 17% decrease of the risk of GDM (OR = 0.830, 95% CI: 0.753-0.914, p = 0.000), 23.6% decrease of the risk of ICP (OR = 0.764, 95% CI: 0.584-0.999, p = 0.049), and 14% decrease of the risk of infertility (OR = 0.860, 95% CI: 0.777-0.951, p = 0.003).</p><p><strong>Conclusion: </strong>Our study indicated that the increased levels of SHBG could significantly reduce the risk of APO. SHBG may be helpful as the indicator for preconception risk assessment and pregnancy risk monitoring. These findings are limited to European and require further validation in diverse populations.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 2","pages":"e70139"},"PeriodicalIF":2.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803206","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":"Outcomes of Ultimpro Testing Implementation for Patients With Unexplained Recurrent Implantation Failure: A Single-Center Retrospective Cohort Study","authors":"Genevieve Genest,&nbsp;Alyssa Hochberg,&nbsp;Martine Boivin,&nbsp;Alexie Ferreira,&nbsp;Zhiyang Liu,&nbsp;Coralie Beauchamp,&nbsp;Marc Beltempo,&nbsp;Michael H. Dahan,&nbsp;Elias M. Dahdouh,&nbsp;Ezgi Demirtas,&nbsp;Robert Hemmings,&nbsp;Wael Jamal,&nbsp;Isaac-Jacques Kadoch,&nbsp;Louise Lapensée,&nbsp;Neal Mahutte,&nbsp;Simon Phillips,&nbsp;Shauna Reinblatt,&nbsp;Camille Sylvestre,&nbsp;William Buckett,&nbsp;Bruce D. Mazer,&nbsp;Ciriaco A. Piccirillo","doi":"10.1111/aji.70131","DOIUrl":"https://doi.org/10.1111/aji.70131","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>A proportion of patients with unexplained recurrent implantation failure (uRIF) may have endometrial immune dysregulation amenable to treatment. Ultimpro (Matrice lab Innove, Paris, France) is an endometrial immunophenotype test which identifies the absence or presence and type of immune dysregulation, proposing personalized protocol adjustments for a future embryo transfer (ET).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>2.5-year single-center retrospective cohort analysis of 121 patients who underwent Ultimpro testing as a pilot study (January 2021—May 2023). Group 1 included 93 patients with uRIF, and Group 2 included 28 patients without RIF. Outcomes from Group 1 were compared to Group 3, a control cohort of 94 uRIF patients, outcomes for Group 2 were compared to Canadian average ongoing pregnancy rates (OPR) per ET. Primary outcome was pregnancy &gt;32 weeks or live birth. Statistical analyses included the Student <i>t</i>-test or Mann–Whitney <i>U</i> test for continuous variables and the Fisher exact test for categorical data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In Group 1, 46/93 (49.5%) patients had a successful pregnancy compared to control (31/94 [33%], <i>p</i> = 0.026); when stratifying for RIF severity, patients with ≥ 5 failed blastocyst transfers benefitted most from Ultimpro (21/38 [55.3%] vs. control 5/25 (20.0%), <i>p</i> = 0.0084). In Group 2, rates of OPR per ET with Ultimpro recommendations did not differ from outcomes for non-RIF patients (9/28 [32.1%]; 95% CI: 0.15–0.52 vs. 46.2%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with uRIF, our preliminary findings suggest that application of Ultimpro recommendations was associated with a higher rate of successful outcomes; this was not the case for patients without RIF. These findings provide the rationale for an independent randomized controlled trial evaluating the large-scale use of Ultimpro in patients with uRIF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740477","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":"Elevated Neutrophil, Lymphocyte, and Platelet Counts as Early Biomarkers of Preeclampsia Risk: A Retrospective Cohort Study","authors":"Ying-Ling Yao,&nbsp;Zhou Xu,&nbsp;Rui Xiao,&nbsp;Er-Han Li,&nbsp;Yong-Jia Zhang,&nbsp;Li-Yang Zhou,&nbsp;Zhao-Hui Zhong,&nbsp;Li-Juan Fu,&nbsp;Hong-Bo Qi,&nbsp;Xiao-Bin Wu,&nbsp;Yu-Bin Ding","doi":"10.1111/aji.70137","DOIUrl":"https://doi.org/10.1111/aji.70137","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to evaluate the association between peripheral immune markers during gestational weeks 11–28 and the risk of preeclampsia (PE), and to explore potential causal relationships using Mendelian randomization (MR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective cohort study involving 19, 028 singleton pregnancies between January 2020 and December 2023. Peripheral immune markers, including neutrophils, lymphocytes, monocytes, and platelets, and derived indices, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII), were analyzed in relation to PE incidence. Subgroup and interaction analyses were further stratified by maternal age, prepregnancy BMI, gestational age at blood test, and gestational diabetes mellitus (GDM). Causality was assessed using MR with the inverse-variance weighted multiplicative random effects (IVW MRE) method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Elevated neutrophil (RR per SD = 1.20; 95% CI: 1.09–1.33; <i>P</i> &lt; 0.001), lymphocyte (RR per SD = 1.16; 95% CI: 1.06–1.27; <i>P</i> = 0.002), and platelet (RR per SD = 1.19; 95% CI: 1.07–1.31; <i>P</i> = 0.001) counts were significantly associated with increased PE risk. Associations were stronger in women aged ≥35 years, with a significant interaction for platelet count (<i>P</i> = 0.004). MR analysis revealed no causal link between genetically predicted immune cell counts and PE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Higher peripheral neutrophil, lymphocyte, and platelet levels are associated with increased PE risk, particularly among older pregnant women. While MR analysis did not support a causal effect, these immune markers may serve as accessible early indicators and offer insight into PE pathogenesis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"94 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725387","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}