Journal of Reproductive Immunology最新文献

{"title":"Assessing the impact and risk of immunomodulatory compounds on pregnancy","authors":"Joanne Kwak-Kim ,&nbsp;Curtis C. Maier ,&nbsp;Caren M. Villano ,&nbsp;Christopher J. Bowman ,&nbsp;Frank R. Brennan ,&nbsp;Dinesh Stanislaus ,&nbsp;Aimee Hillegas ,&nbsp;John Krayer ,&nbsp;Rodney A. Prell ,&nbsp;Tracey L. Papenfuss ,&nbsp;Annick Cauvin ,&nbsp;Joshua Gamse ,&nbsp;Anna Dahlman ,&nbsp;Brian Enright ,&nbsp;Lawrence Leshin ,&nbsp;Gautham K. Rao ,&nbsp;Whitney Helms ,&nbsp;Claudette L. Fuller ,&nbsp;Xiuhua Yang ,&nbsp;Connie Chen ,&nbsp;Shermaine Mitchell-Ryan","doi":"10.1016/j.jri.2025.104453","DOIUrl":"10.1016/j.jri.2025.104453","url":null,"abstract":"<div><div>There have been remarkable advancements in understanding the complex and dynamic immune biological processes engaged during all stages of pregnancy. Exquisite control of immune processes is critical to successful outcome in all stages of pregnancy from ovulation to birth. There are many immunomodulatory therapeutics that may offer beneficial treatment options for a variety of diseases (e.g., inflammation/autoimmunity, cancer) to patients that are or desire to become pregnant. It is important to understand the potential for these immunomodulatory therapeutics to alter the critical immune processes in pregnancy to inform clinical risk relative to successful pregnancy. The Health and Environmental Sciences Institute-Developmental and Reproductive Toxicology/Immuno-safety Technical Committee (HESI DART/ITC) conducted a survey on approaches to assess adverse pregnancy outcomes with immunomodulators. HESI DART/ITC also organized a workshop for an extended discussion on immune mechanisms during pregnancy, the adequacy of current tools/methodologies to identify concerns for potential pregnancy hazards from immunomodulatory therapies, ways to identify and address scientific gaps, and global regulatory considerations across various immunomodulatory modalities and indications. In this manuscript we summarize learnings from these efforts to characterize risk within this patient population, promote more informed treatment decisions, and enable safer pharmacological interventions during pregnancy.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104453"},"PeriodicalIF":2.9,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479519","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":"Placental volume as a potential early marker for metabolic pertubations during pregnancy","authors":"Ann-Christin Tallarek ,&nbsp;Angelo Sirico ,&nbsp;Janina Goletzke ,&nbsp;Mirja Pagenkemper ,&nbsp;Evelyn Huhn ,&nbsp;Gudula Hansen ,&nbsp;Felix Stahl ,&nbsp;Petra Clara Arck ,&nbsp;Anke Diemert","doi":"10.1016/j.jri.2025.104456","DOIUrl":"10.1016/j.jri.2025.104456","url":null,"abstract":"<div><div>The placenta has a central function in fetal glucose supply and placental volume has received rising awareness as a potential predicting factor for adverse pregnancy outcomes. We aimed to examine whether placental volume is a prognostic marker for metabolic perturbations affecting both mother and child. Data from 100 women participating in a longitudinal cohort study of healthy pregnant women were obtained. Placental volume was assessed via transabdominal ultrasound at gestational weeks 12–14. Additional ultrasound measurements were conducted at gestational weeks 23–25, 28–30, and 34–36 to assess fetal anthropometry. HbA1c was measured in first trimester blood samples. Both cross-sectional and prospective associations between first trimester placental volume and selected fetal and maternal parameters were examined using multivariable linear regression models. Interactions by gender were observed for associations with HbA1c, anterior abdominal wall thickness (AAWT), gestational weight gain and estimated fetal weight. A higher first trimester placental volume was related to higher HbA1c levels in the first trimester, higher AAWT measures in the third trimester, and greater gestational weight gain in women carrying a male fetus only (all p = 0.02). In women carrying a female fetus, a positive association was observed between placental volume and estimated fetal weight at gestational week 34–36 (p = 0.045). None of the other maternal or fetal parameters were related to placental volume (p ≥ 0.1). Our results indicate first trimester placental volume to be a potential prognostic factor for maternal glucose metabolism and both fetal and maternal anthropometric perturbations particularly for those mothers carrying a male fetus.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104456"},"PeriodicalIF":2.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429876","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":"Immunoglobulin therapy for infertility and the role of immune cells in pregnancy success: An extensive investigation and update","authors":"Lida Aslanian-kalkhoran ,&nbsp;Narjes Nouri ,&nbsp;Mohammad Sadegh Soltani-Zangbar ,&nbsp;Amirhossein Mardi ,&nbsp;leili Aghebati-Maleki","doi":"10.1016/j.jri.2025.104458","DOIUrl":"10.1016/j.jri.2025.104458","url":null,"abstract":"<div><div>In the United States, roughly one out of every eight couples, or 7.5 million women, experience challenges related to conceiving or maintaining a pregnancy. The body's immune response is vital during pregnancy. T cells, natural killer (NK) cells, B cells, and macrophages (MQ) are immune cells in the female reproductive tract. They are in charge of maintaining tissue homeostasis and regulating the immune system's response to invasive pathogens. Failure to regulate these immune cells might result in inflammation, which reduces fertility. The immune system modulation of pregnancy loss has been studied with intralipid, intravenous immunoglobulin (IVIG), and paternal leukocyte vaccination. A concentrated antibody called intravenous immunoglobulin (IVIG) is utilized as a biological agent to treat autoimmune, viral, and inflammatory diseases and some immunodeficiencies. The main objective of this treatment is to restore a damaged immune system. IgGs, through binding to specific antigens, promote the innate immunity's cellular and humoral immune response by activating complements and binding to Fc receptors of several immune cells. Contrariwise, IVIG regulates pathogenic autoimmunity in animal models, including skin-blister diseases, nephrotoxic nephritis, and K/BxN arthritis. IVIG has, therefore, been of great interest as an immune modulator in several immune disorders. This review aims to investigate the immunological reasons of reproductive failure, focusing on the immunomodulatory effects of IVIG in its treatment.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104458"},"PeriodicalIF":2.9,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509670","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":"Sexual and reproductive health in overweight and obesity: Aims and visions for integrated research approaches","authors":"Marie Albrecht ,&nbsp;Nina Reitis ,&nbsp;Mirja Pagenkemper ,&nbsp;Ann-Christin Tallarek ,&nbsp;Laura Pietras ,&nbsp;Thula Koops ,&nbsp;Dimitra E. Zazara ,&nbsp;Anastasios D. Giannou ,&nbsp;Mariana G. Garcia","doi":"10.1016/j.jri.2025.104454","DOIUrl":"10.1016/j.jri.2025.104454","url":null,"abstract":"<div><div>Overweight and obesity increasingly affect women in their reproductive phase, during family planning, pregnancy, breastfeeding and the postpartum period. Overweight and obesity are associated with impaired sexual and reproductive health, including increased rates of infertility, pregnancy complications, and reduced breastfeeding rates. Furthermore, maternal overweight and obesity are associated with long-term negative health consequences for the child, such as an increased risk for respiratory and metabolic disease. With the Junior Research Center for Reproduction: Sexual and Reproductive Health in Overweight and Obesity (SRHOO Center), we aim to address the effects of overweight and obesity on sexual and reproductive health in an interdisciplinary approach, combining the areas of obstetrics and midwifery, sexual health research, basic research in feto-maternal medicine and glycoimmunology, pediatrics, as well as endocrinology, metabolism and bariatric surgery. Combining these areas of expertise, we seek (1) to understand the effects of overweight and obesity on sexual and reproductive health in different patient groups, focusing on their specific needs in order to provide appropriate counselling and access to healthcare; (2) to improve reproductive health in different groups of overweight and obese patients; and (3) to create interdisciplinary, comprehensive scientific and clinical training regarding sexual and reproductive health in overweight and obese patients. In this short introduction to the SRHOO Center, we provide information on its structure, aims and individual projects as well as its presumed long-term implications for clinical care and public health.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104454"},"PeriodicalIF":2.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454683","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":"Future perspectives of fertility protection","authors":"Karin Bundschu ,&nbsp;Silviya Aleksandrova-Yankulovska ,&nbsp;Christian Denzer ,&nbsp;Tana Dornbrach ,&nbsp;Sabine Eberhart ,&nbsp;Lazar Glisic ,&nbsp;Ana Gomes Barata ,&nbsp;Harald Gündel ,&nbsp;Klaus Hönig ,&nbsp;Wolfgang Janni ,&nbsp;Karamdeep Khinda ,&nbsp;Laura Rafensteiner ,&nbsp;Reiner Siebert ,&nbsp;Florian Steger ,&nbsp;Stephan Stilgenbauer ,&nbsp;Martin Wabitsch ,&nbsp;Lisa Wiesmüller ,&nbsp;Miriam Wilhelm ,&nbsp;Birgit Wojak ,&nbsp;Katharina Hancke","doi":"10.1016/j.jri.2025.104455","DOIUrl":"10.1016/j.jri.2025.104455","url":null,"abstract":"<div><div>Reproductive health is of major importance for individuals, for the society and for the health of future generations. This includes physical and medical dimensions as well as psychosocial and ethical ones. Whenever the possibility of starting a family is compromised, either due to an oncological cytotoxic treatment or due to transgender hormone medication with the aim to align their secondary sexual characteristics or other medical or social conditions, one key aspect of reproductive health is fertility protection. However, as a very young field in medicine, there are still many research questions that need to be clarified to provide the best possible treatment for affected people. These include the optimization and safety of cryopreservation processes of germ cells in women, men, transgender people, adolescents and children. Another focus is on psychological care as well as ethical, economic and legal issues. The establishment and development of the center for fertility protection Ulm (<strong>FePro-Ulm</strong>) will focus on a detailed molecular biological and (epi)genetic understanding of the underlying processes in ovarian tissue, oocytes and sperm to improve and develop new diagnostic and therapeutic approaches. The individual needs of affected people, their partners and families will be evaluated by an interdisciplinary approach. The collaborations within FePro-Ulm will develop preventative and helpful interventions for affected people. In addition, a better awareness of this important topic of reproductive health and fertility protection will be addressed by including participation representatives and strengthen public relation works.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104455"},"PeriodicalIF":2.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429957","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":"T lymphocytes in human milk: Their role in immune system maturation through maternal microchimerism","authors":"Ayamita Paul,&nbsp;Tram Bui,&nbsp;Mariana Muelbert ,&nbsp;Gergely Toldi","doi":"10.1016/j.jri.2025.104451","DOIUrl":"10.1016/j.jri.2025.104451","url":null,"abstract":"<div><div>Breastfeeding promotes the trafficking of immune cells and soluble factors from the mother to the neonate during lactation, resulting in maternal microchimerism. Human milk is abundant in T lymphocytes, but little is known about their priming and actions in neonatal mucosal tissues and their role in conferring immune tolerance in early life. This review summarises recent findings on the characteristics of human milk T cells compared to their counterparts in maternal and neonatal blood. We discuss how bioactive components of human milk, such as cytokines, hormones, and miRNA, may modulate the immune suppressive function of this cell subset. We shed light on the presence and possible functions of regulatory T cells (Tregs) in the breastfeeding triad of mother, human milk, and neonate, and how this subset of T lymphocytes may contribute to the prevention of immune pathologies, such as allergies and autoimmune diseases, later in life through human milk-induced maternal microchimerism in the newborn.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104451"},"PeriodicalIF":2.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402551","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":"Characteristics of maternal-placental vascular malperfusion and its correlation with neonatal adverse outcomes","authors":"Huabo Jiang ,&nbsp;Dayuan Shi ,&nbsp;Luyao Cai ,&nbsp;Yao Zhang ,&nbsp;Qianqian Sun ,&nbsp;Hongyan Jiang ,&nbsp;Xinyao Zhou ,&nbsp;Xing Wei ,&nbsp;Qizhi He ,&nbsp;Luming Sun","doi":"10.1016/j.jri.2025.104452","DOIUrl":"10.1016/j.jri.2025.104452","url":null,"abstract":"<div><h3>Introduction</h3><div>Fetal growth restriction (FGR) is the failure of fetal growth to attain inherent genetic potential owing to a diverse array of factors. Limited studies have investigated the correlation between varying levels of maternal-placental vascular malperfusion (MVM)-type FGR and adverse neonatal outcomes. Thus, we sought to explore the maternal-fetal characteristics of different degrees of MVM-type FGR and their correlation with adverse neonatal outcomes.</div></div><div><h3>Methods</h3><div>We collected all cases of FGR from 2018 to 2023 and observed the pregnancy, delivery, and newborn characteristics of FGR cases managed by a fetal medical center. General information, clinical examinations, and neonatal outcomes were recorded. Placental lesions were sampled and classified according to the 2016 Amsterdam standard, then divided into two groups based on MVM level: low-grade and high-grade.</div></div><div><h3>Results</h3><div>The high-grade MVM-type FGR group (30/94) had a higher prevalence of pregnant mothers with diabetes mellitus (P＝0.022) and hypertension (P＝0.013), higher incidence of abnormal umbilical artery pulsatility index (UA-PI) (P＝0.022) and uterine artery pulsatility index (UtA-PI) (P &lt; 0.001), higher incidence of incomplete distal villus development (P＝0.027) and placental vascular disease (P＝0.008), higher incidence of cerebral hemorrhage (P＝0.006) and poor outcomes (P＝0.04), lower fetal weight (P＝0.026), and longer hospital stays for newborns (P＝0.018). Logistic regression analysis showed that body mass index (P＝0.04), diabetes (P＝0.033), assisted reproduction (P＝0.048), pathological placental villus overmaturity (P＝0.033) High-grade MVM (P＝0.014) were independent risk factors for adverse neonatal outcomes, fetal birth weight (P＝0.004) is an independent protective factor.</div></div><div><h3>Discussion</h3><div>High-grade MVM FGR is associated with the incidence rate of adverse neonatal outcomes, with a series of differences in the pre-pregnancy state, clinical auxiliary examination, and pathological characteristics compared with low grade MVM. Simultaneously, we found five independent risk factors and one protective factor that led to adverse neonatal outcomes in MVM group.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104452"},"PeriodicalIF":2.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402550","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":"Targeting the lncRNA GAS5/TLR4/NLRP3 signaling cascade inhibits endometrial stromal cell pyroptosis and prevents the progression of intrauterine adhesions","authors":"Yifeng Zhang ,&nbsp;Dongjie Wang ,&nbsp;Xiaomei Wu ,&nbsp;Ting Zhao ,&nbsp;Ming He ,&nbsp;Yunyu He ,&nbsp;Chunmei Meng","doi":"10.1016/j.jri.2025.104450","DOIUrl":"10.1016/j.jri.2025.104450","url":null,"abstract":"<div><div>Intrauterine adhesion (IUA) poses a serious threat to women's health, and its specific pathogenesis has not yet been elucidated. Our study found through high-throughput sequencing that differentially expressed genes of the endometrial tissues from healthy individuals or IUA patients were enriched in the toll-like receptor (TLR), nuclear factor-kappa B (NF-kB), and nucleotide-binding oligomerization domain-like receptor (NLR) signaling pathways. Meanwhile, we observed that compared to the controls, long non-coding RNA (lncRNA) growth arrest-specific transcripts 5 (GAS5) was significantly upregulated in the endometrial tissue of IUA patients and scratching/lipopolysaccharide (LPS)-induced IUA model mice. Subsequently, results from the functional verification assay, including hematoxylin-eosin staining, enzyme-linked immunosorbent assay, and western blot, showed that knockdown of GAS5 improved endometrial injury and uterine adhesions, decreased the levels of TIMP1, α-SMA, Vimentin, and COL1A1, but elevated MMP9 level to reduce excessive accumulation of extracellular matrix (ECM), and inhibited the expression of NLRP3, cleaved caspase-1, GSDMD, and nuclear p65 to ameliorate pyroptosis in IUA model mice. As confirmed by bioinformatics analysis and dual luciferase reporter gene system, GAS5 sponged microRNA (miR)-205–5p to upregulate TLR4, further activating the NF-kB and NLRP3 signaling in endometrial stromal cells (ESCs). The <em>in vitro</em> functional recovery experiments suggested that GAS5 knockdown alleviated LPS-induced activation of the NF-kB and NLRP3 signaling, pyroptotic cell death, and ECM deposition in ESCs, which was counteracted by overexpressing TLR4 and NLRP3. In a word, our study proved that targeting the GAS5/TLR4/NLRP3 signaling cascade inhibits ESCs pyroptosis and prevents the progression of IUA, providing promising therapeutic strategies for IUA disease.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104450"},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395717","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":"The impact of MTHFR and VDR polymorphisms on endometriosis susceptibility: Insights from a systematic review and meta-analysis","authors":"Ruting Zhang ,&nbsp;Hanxin Lv ,&nbsp;Jinghua Liu ,&nbsp;Jiashan Yin ,&nbsp;Shuang Wu ,&nbsp;Yuyang Xie ,&nbsp;Huihui Xing ,&nbsp;Rui Wang ,&nbsp;Zefan Zhao ,&nbsp;Bimin Shi ,&nbsp;Xiaoqin Yang ,&nbsp;Shangshang Gao","doi":"10.1016/j.jri.2025.104449","DOIUrl":"10.1016/j.jri.2025.104449","url":null,"abstract":"<div><div>The <em>VDR</em> and <em>MTHFR</em> polymorphisms have been linked to many gynecological and obstetrical diseases. However, there is still a pressing need for a systematic review and meta-analysis to synthesize the current evidence on the association between these variants and endometriosis risk. English and Chinese literature databases were systematically retrieved to find relevant research published up to August 1, 2024. The meta-analytic calculations were implemented in the R language 4.4.1 environment. The odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were estimated to assess the magnitude of the effect. In total, 26 datasets comprising 9300 subjects were included. The pooled estimate demonstrated a significant association between the <em>MTHFR</em> C677T polymorphism and endometriosis susceptibility in the allele model (OR: 1.41, 95 % CI: 1.07–1.86, <em>P</em> = 0.01), homozygote model (OR: 2.09, 95 % CI: 1.56–2.79, <em>P</em> &lt; 0.01), dominant model (OR: 1.48, 95 % CI: 1.06–2.07, <em>P</em> = 0.02), and recessive model (OR: 1.81, 95 % CI: 1.38–2.37, <em>P</em> &lt; 0.01). However, the meta-analysis for the <em>MTHFR</em> A1298C polymorphism and the <em>VDR Fok</em>I, <em>Taq</em>I, <em>Apa</em>I, and <em>Bsm</em>I polymorphic variants did not find statistical significance. In conclusion, this meta-analysis suggests that the <em>MTHFR</em> C677T polymorphism might play a role in developing endometriosis disease. Meanwhile, further large-scale validations that consider multiple factors are warranted to confirm this finding.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104449"},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388170","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":"Endoplasmic reticulum stress and unfolded protein response play roles in recurrent pregnancy loss: A bioinformatics study","authors":"Yi Jiang ,&nbsp;Qingxia You ,&nbsp;Fangxiang Mu ,&nbsp;Shiqing Xiang ,&nbsp;Nian Zhang","doi":"10.1016/j.jri.2025.104446","DOIUrl":"10.1016/j.jri.2025.104446","url":null,"abstract":"<div><div>This study aims to explore whether endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) processes could be potential targets for preventive, diagnostic, and therapeutic for recurrent pregnancy loss (RPL). RPL datasets GSE165004 and GSE26787 were sourced from the GEO database, and ERS- and UPR-related gene sets were obtained from the MsigDB database. After differentially expressed genes (DEGs) identification, key genes were screened from intersecting DEGs in RPL-ERS and RPL-UPR datasets. The z-score algorithm was conducted to obtain phenotype scores. Functional enrichment and machine learning analyses were performed to assess gene function and diagnostic value evaluation. Interaction networks were conducted to investigate upstream regulated relationships of the key genes. Immune infiltration and single-cell RNA sequencing (scRNA-seq) were assessed to explore ERS and UPR functions at the cellular level. Totally 25 key genes RPL-ERS DEGs and 16 key genes RPL-UPR DEGs were identified. Among them, six key genes (NFYB, EXOSC2, UBQLN2, RNF139, DERL1, and FBXO27) were validated to show consistent expression trends in both RPL datasets. Functional enrichment highlighted their involvement in the immunity of RPL. Machine learning indicated the significant diagnostic value of these validated genes for RPL, with an accuracy rate of &gt; 80 %. scRNA-seq analysis revealed elevated ERS and UPR expressions in monocytes/macrophages in RPL samples. In conclusion, ERS and UPR processes are associated with RPL occurrences, and were mainly upregulated in monocytes/macrophages within RPL samples. ERS and UPR processes may serve as potential targets for the prevention, diagnosis, and treatment of RPL.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"168 ","pages":"Article 104446"},"PeriodicalIF":2.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350165","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}