Journal of Reproductive Immunology最新文献

{"title":"PD-L1 gene variants as predictors of recurrent pregnancy loss: A case-control study among Kazakh women in Central and West Kazakhstan","authors":"Wassim Y. Almawi ,&nbsp;Gulzhanat Aimagambetova ,&nbsp;Abay Tursunov ,&nbsp;Akbayan Turesheva ,&nbsp;Aizada Marat ,&nbsp;Aktoty Ilmaliyeva ,&nbsp;Kuralay Atageldiyeva","doi":"10.1016/j.jri.2025.104524","DOIUrl":"10.1016/j.jri.2025.104524","url":null,"abstract":"<div><div>Emerging evidence implicates immune dysfunction in maintaining maternal-fetal tolerance, particularly the programmed death-ligand 1 (PD-L1) pathway. The association between <em>PD-L1</em> gene variants and recurrent pregnancy loss (RPL) in women from Central and West Kazakhstan was investigated, and correlations between PD-L1 genotypes and demographic or clinical features were explored. This case-control study included 197 women with RPL and 198 controls of ethnically Kazakh women. Genotyping of rs2297136, rs2297137, rs4143815, rs822336, and rs822337 <em>PD-L1</em> variants was performed by real-time PCR. Demographic and clinical characteristics did not differ significantly between RPL cases and controls from Central and West Kazakhstan. Significant associations were found in the West Kazakhstan cohort for rs822336 (p = 0.02) and rs822337 (p = 0.004). The G/C genotype of rs822336 (OR = 2.33, 95 % CI = 1.04–5.26) and rs822337 (OR = 308, 95 % CI = 1.34–7.04) was associated with an increased risk of RPL in West Kazakhstan cohort. Haplotype analysis revealed a significant association of the GTGAG haplotype with RPL in West Kazakhstan (p = 0.018) but not in Central Kazakhstan subjects. Correlation analysis showed that rs822336 was positively correlated with age and BMI (p &lt; 0.05) in Central Kazakhstan, while rs822337 was negatively correlated with live births in West Kazakhstan (p &lt; 0.05). The findings underscore population-specific genetic influences on RPL risk, with notable significant associations between RPL and <em>PD-L1</em> SNPs and GTGAG haplotype in the West Kazakhstan cohort but not in the Central Kazakhstan cohort. This highlights the contribution of genetic factors to RPL pathogenesis in different populations.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104524"},"PeriodicalIF":2.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705957","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":"Mechanism of FBXW7 mRNA degradation mediated by circSMAD2 through METTL3-METTL14 m6A axis affects proliferation and invasion of endometrial stromal cells","authors":"Yuan Peng,&nbsp;Ping Wang,&nbsp;Yanqin Lou,&nbsp;Donghua Wang","doi":"10.1016/j.jri.2025.104523","DOIUrl":"10.1016/j.jri.2025.104523","url":null,"abstract":"<div><div>This study investigates the role of circSMAD2 in ectopic endometrium of endometriosis (EMS) patients, focusing on its upregulation of FBXW7 m6A level by mediating the formation of the METTL3/METTL14 complex. Ectopic endometria from EMS patients and healthy individuals were compared for the expression levels of FBXW7 and YTHDF2, as well as total m6A levels. Results showed elevated FBXW7 and reduced YTHDF2 expressions in EMS ectopic endometria, along with decreased m6A levels. YTHDF2 was found to bind to FBXW7 mRNA, leading to its degradation and suppression of FBXW7 expression. CircSMAD2 interacted with METTL3/METTL14 complex in human endometrial stromal cells, increasing FBXW7 m6A level without affecting complex expression levels. Overexpression of YTHDF2 or circSMAD2 inhibited cell proliferation, migration, and invasion, effects partly reversed by FBXW7 overexpression. Reduced circSMAD2 expression in EMS resulted in decreased METTL3/METTL14 complex formation and FBXW7 m6A levels, while decreased YTHDF2 expression in EMS led to higher FBXW7 expression, promoting cell proliferation and invasion. This study sheds light on the regulatory mechanism of circSMAD2 in EMS pathogenesis.</div></div><div><h3>Data Availability</h3><div>The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104523"},"PeriodicalIF":2.9,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759502","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":"Evaluation of peripheral NK tests offered to women with recurrent pregnancy loss and a search for novel candidate biomarkers","authors":"Danai Bagkou Dimakou ,&nbsp;Jennifer Tamblyn ,&nbsp;David Lissauer ,&nbsp;Alex Richter","doi":"10.1016/j.jri.2025.104522","DOIUrl":"10.1016/j.jri.2025.104522","url":null,"abstract":"<div><div>Recurrent pregnancy loss (RPL) is a common condition of largely undetermined pathogenesis. There is prior evidence of association with immune dysregulation linked to elevated NK cell levels and cytotoxicity. However, experimental findings remain contentious, hindering clinical adoption of immunological testing. Given their importance in healthy pregnancy, this study set out to determine the clinical utility of NK cell assays in 100 non-pregnant women with RPL and 80 healthy control women and establish an exploratory mass cytometry panel for in-depth NK phenotyping. As previously described, peripheral NK cell elevation was observed with RPL. The augmented NK cell cytotoxicity, often referenced, was undetectable, although enhanced degranulation was observed. Reduced cytolytic molecule secretion by PBMCs was seen in RPL, possibly counterbalancing the increased NK cell degranulation. Mass cytometry was employed for the detailed investigation of NK cell phenotype, focused on inhibitory and activating receptor expression. Augmented prevalence of CD57⁺ mature cytotoxic NK cells was present in the RPL cohort. This was accompanied by elevated prevalence of subsets lacking inhibitory receptor expression, indicating enhanced NK cell responsiveness to activating signalling. Additionally, CXCR3/CXCR4⁺ subset reduction, suggested potential uterine migration defects. This extensive analysis of peripheral NK cells in RPL has revealed significant dysregulation affecting both total number and potential activity. The extent to which this dysregulation is reflected <em>in utero</em> requires further examination. Current findings will be used to guide subsequent investigations on paired peripheral and endometrial samples as well as biomarker discovery to improve our capacity to estimate risk of a following loss.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104522"},"PeriodicalIF":2.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670238","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":"Non-invasive blood tests for earlier diagnosis and treatment of endometriosis","authors":"Behnaz Sadeghzadeh Oskouei ,&nbsp;Zoleikha Asadi ,&nbsp;Rana Jahanban Esfahlan","doi":"10.1016/j.jri.2025.104521","DOIUrl":"10.1016/j.jri.2025.104521","url":null,"abstract":"<div><div>Endometriosis is a chronic condition characterized by the presence of endometrial-like tissue outside the uterus, leading to symptoms such as dysmenorrhea and chronic pain. It affects approximately 2–10 % of women of reproductive age and up to 50 % of those experiencing infertility, significantly impacting the healthcare system. Despite its prevalence, endometriosis presents in a variety of forms and phenotypes, partly due to the absence of a non-invasive biomarker for diagnosis. Early detection of endometriosis is crucial for effective management; however, the most dependable diagnostic method currently available is laparoscopy. Many women are reluctant to undergo this surgical procedure, resulting in a substantial number remaining unaware of their condition. This review aims to explore the potential of non-invasive blood tests in developing reliable biomarkers or a combination of biomarkers for the early detection and diagnosis of endometriosis. Innovative therapies such as immunomodulation, stem cell therapy, biosensors, and nanotheranostics present promising avenues for personalized diagnosis and treatment, focusing on genetic, epigenetic, and immunological aspects. The review emphasizes the importance of various biomarkers and the necessity for further research to enhance diagnosis and improve the quality of life for women affected by endometriosis.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104521"},"PeriodicalIF":2.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684753","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":"Inhibition of interleukin-1 signaling protects against Group B streptococcus-induced preterm birth and fetal loss in mice","authors":"Peck Y. Chin ,&nbsp;Lachlan M. Moldenhauer ,&nbsp;William D. Lubell ,&nbsp;David M. Olson ,&nbsp;Sylvain Chemtob ,&nbsp;Jeffrey A. Keelan ,&nbsp;Sarah A. Robertson","doi":"10.1016/j.jri.2025.104520","DOIUrl":"10.1016/j.jri.2025.104520","url":null,"abstract":"<div><div>Group B streptococcus is a common microbial agent associated with spontaneous preterm birth and fetal inflammatory response syndrome. In this study, we evaluated the utility of rytvela, a novel peptide antagonist of the interleukin-1 receptor, to suppress inflammatory activation, prolong gestation and improve neonatal outcomes induced in mice by Group B streptococcus. Pregnant mice were administered rytvela or PBS on gestation day 16.5, immediately prior and following surgical administration of heat-killed Group B streptococcus (hkGBS) or PBS into the uterine cavity. Treatment with rytvela prevented preterm delivery and alleviated fetal demise <em>in utero</em> and in the perinatal phase elicited by hkGBS. Compared to pups exposed to hkGBS alone, pups of dams co-administered rytvela exhibited substantially improved survival and growth through to weaning. Analysis by qPCR showed expression of inflammatory cytokine genes <em>Il1b</em>, <em>Il6, Tnf,</em> and <em>Ifng</em> in uterine tissues, and <em>Il1b</em>, <em>Il6,</em> and <em>Tnf</em> in fetal membranes, were stimulated by hkGBS and this increase was suppressed by co-administration of rytvela. Premature induction of uterine activation gene <em>Ptgs2</em> in the myometrium was also attenuated by rytvela treatment. These data show that activation of IL1-mediated signaling in response to Group B streptococcus triggers an inflammatory cascade that causes preterm parturition and fetal inflammatory injury, and that rytvela can suppress inflammatory mediators to substantially improve pregnancy and fetal outcomes. Our findings add to accumulating evidence supporting clinical investigation of rytvela for fetal protection and delaying preterm birth.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104520"},"PeriodicalIF":2.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143696084","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":"Melatonin alleviates endometrial fibrosis in bovine endometritis by regulating TGF-β/Smad and MAPK signaling pathways via MT2","authors":"Yi Zhou ,&nbsp;Xingyi Chen ,&nbsp;Zihao Fang ,&nbsp;Limin Qiao ,&nbsp;Yue Jiang ,&nbsp;Liangli Song ,&nbsp;Xianghong Du ,&nbsp;Hua Yao ,&nbsp;Longfei Xiao","doi":"10.1016/j.jri.2025.104519","DOIUrl":"10.1016/j.jri.2025.104519","url":null,"abstract":"<div><div>Bovine endometritis can lead to abnormal endometrial function and fibrosis, resulting in difficulties in successful embryo implantation and intrauterine adhesions. Melatonin is well known for its profitable effects against inflammation and pathological fibrosis in discrepant organs. Considering the potential therapeutic benefits of melatonin, this study aimed to investigate its effects on endometrial fibrosis in cows with endometritis. Firstly, we evaluated the expression patterns of various factors associated with fibrosis, such as transforming growth factor-β1 (TGF-β1), extracellular matrix (ECM)-related markers (<em>COL1A1</em> and <em>COL3A1</em>), epithelial-mesenchymal transformation (EMT)-related proteins (α-SMA and Vimentin) in healthy and endometritis-affected bovine uterine tissues. The results showed that diseased tissues presented significantly higher TGF-β1 expression, ECM production, and EMT progression versus normal tissues. Moreover, we established an LPS-induced fibrosis model in endometrial stromal cells (ESCs), and found that melatonin inhibited the fibrosis process of ESCs in a dose-dependent manner. The MT2 inhibitor 4P-PDOT blocked the antifibrotic effects of melatonin and inhibited the phosphorylation of Smad2/3, ERK1/2, and JNK1/2 in LPS-induced fibrosis of ESCs, but not P38 MAPK. These data implied that melatonin supplementation attenuated LPS-induced fibrosis in ESCs by modulating the inhibition of TGF-β/Smad, ERK, and JNK signaling pathways via MT2.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104519"},"PeriodicalIF":2.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628467","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":"Multidisciplinary assessment of the impact of assisted reproductive techniques on pregnancy and long-term outcomes of mother and child: Foundation of the LE-REP (Leipzig Reproductive Health) Center","authors":"Marie Luise Münch ,&nbsp;Massimiliano Lia ,&nbsp;Benjamin Wolf ,&nbsp;Moritz Köhler ,&nbsp;Ronny Baber ,&nbsp;Kunal Singh ,&nbsp;Anne Schumacher ,&nbsp;Tobias Kretschmer ,&nbsp;Rita Grabowska ,&nbsp;Katja Linde ,&nbsp;Viktoria Schmidt ,&nbsp;Martin Kramuschke ,&nbsp;Julia Bartley ,&nbsp;Noura Kabbani ,&nbsp;Mandy Vogel ,&nbsp;Yujia Guo ,&nbsp;Shrey Kohli","doi":"10.1016/j.jri.2025.104457","DOIUrl":"10.1016/j.jri.2025.104457","url":null,"abstract":"<div><div>About 8–10 % of all people of reproductive age are unable to conceive children. In recent years, an increased number of consultations for fertility treatments has been observed with a continuing positive trend. It is known that infertility itself and assisted reproductive technologies (ARTs) are frequently associated with recurrent miscarriages, pregnancy complications or psychosocial problems. In parallel, metabolic and vascular diseases and obesity are becoming a growing issue, even among the younger population, and are affecting fertility and pregnancy outcomes of mother and child. Possible interactions between these conditions and the underlying mechanisms are not well understood hitherto. Furthermore, reproductive outcomes are increasingly challenged by the potential effects of environmental pollution on key reproductive processes, including oocyte maturation and atresia, sperm quality, implantation as well as their role in recurrent miscarriages. The Leipzig reproductive health (LE-REP) project is aimed at investigating the interplay between ARTs and the aforementioned reproductive challenges, including different aspects of fertility problems, early and late pregnancy as well as long-term effects on mothers and their children born via fertility treatment. This multidisciplinary initiative is expected to provide a deep understanding of underlying mechanisms, providing a framework for future preventive strategies improving reproductive health. Finally, LE-REP aims to establish a high-level university fertility center of excellence, combining advanced clinical care, cutting-edge research and education to train future reproductive medicine specialists.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104457"},"PeriodicalIF":2.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628466","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":"Mendelian randomization reveals causal relationships between cytokines and male reproductive diseases","authors":"Jie Ding","doi":"10.1016/j.jri.2025.104465","DOIUrl":"10.1016/j.jri.2025.104465","url":null,"abstract":"<div><div>This study aims to explore the causal links between cytokines and four male reproductive disorders, namely abnormal spermatozoa (AS), male infertility, erectile dysfunction (ED), and hyperplasia of prostate (HP), employing a two-sample Mendelian randomization (MR) approach. Genetic associations with male reproductive diseases were derived from the IEU OpenGWAS project, with cytokine data from two GWASs focused on the human proteome and cytokines. Estimations were derived using inverse variance weighting, MR-Egger regression, weighted median, weighted model, and simple mode. Furthermore, the robustness of the findings was evaluated through Cochran’s Q-test, MR-Egger regression, and leave-one-out sensitivity analysis. Fifteen unique cytokines were identified as having causal relationships with the risk of four male reproductive disorders. Specifically, for AS, interleukin-22 (IL-22), IL-12, and macrophage migration inhibitory factor were negatively correlated with AS, while tumor necrosis factor β levels were positively correlated with AS. In the context of male infertility, IL-2 receptor antagonist levels, IL-34, and granulocyte-colony stimulating factor levels were positively linked to male infertility, whereas IL-21 showed a negative relationship. Regarding ED, IL-19, IL-1β, and eotaxin levels were negatively associated with ED risk, while macrophage inflammatory protein 1β (MIP-1β) levels and interferon gamma-induced protein 10 levels were positively associated. As for HP, stromal-cell-derived factor 1α levels and MIP-1α levels revealed negative associations with HP. In conclusion, this MR analysis revealed that several cytokines were causally associated with male reproductive diseases and could be valuable in offering new insights for further mechanistic and clinical investigations of cytokines-associated male reproductive diseases.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104465"},"PeriodicalIF":2.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512287","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 role of necroptosis in pathological pregnancies: Mechanisms and therapeutic opportunities","authors":"Lidan He ,&nbsp;Shan Zheng ,&nbsp;Feng Zhan ,&nbsp;Na Lin","doi":"10.1016/j.jri.2025.104460","DOIUrl":"10.1016/j.jri.2025.104460","url":null,"abstract":"<div><div>Necroptosis, a distinctive form of programmed cell death differs mechanistically from apoptosis pyroptosis, and autophagy, is characterized by the activation of receptor-interacting protein kinases (RIPK1/RIPK3) and their downstream effector, mixed lineage kinase domain-like protein (MLKL). This programmed cell death pathway serves as a crucial mediator of inflammatory responses and has been implicated in the pathogenesis of diverse pathological conditions. Recent evidence has implicated dysregulated necroptosis in the pathogenesis of severe pregnancy complications, including preeclampsia (PE), fetal growth restriction (FGR), recurrent spontaneous abortion (RSA), and gestational diabetes mellitus (GDM). In these disorders, necroptosis promotes placental dysfunction through multiple interconnected mechanisms: amplification of pro-inflammatory cytokine cascades, aberrant immune activation, disruption of plasma membrane integrity, and subsequent tissue injury.These pregnancy-related pathologies consistently demonstrate elevated necroptotic signatures, correlating with adverse maternal-fetal outcomes. This comprehensive review synthesizes current understanding of the molecular mechanisms underlying necroptosis, with particular emphasis on its pivotal role in the etiopathogenesis of pregnancy-related disorders. Furthermore, we critically evaluate the therapeutic potential of targeting the necroptotic signaling axis, providing novel perspectives for developing targeted interventions to improve clinical outcomes in complicated pregnancies.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104460"},"PeriodicalIF":2.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512288","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":"Endometriosis: A new perspective on epigenetics and oxidative stress","authors":"Yu Guan ,&nbsp;Yawen Chen ,&nbsp;Rong Lin ,&nbsp;Tinghui Mo ,&nbsp;Shiyu Li ,&nbsp;Ying Cao ,&nbsp;Tailang Yin ,&nbsp;Lianghui Diao ,&nbsp;Yuye Li","doi":"10.1016/j.jri.2025.104462","DOIUrl":"10.1016/j.jri.2025.104462","url":null,"abstract":"<div><div>As a complex chronic gynecological disorder characterized by multifaceted etiology involving genetics, environment, immunity and inflammation, endometriosis (EM) has long been a significant concern for women of reproductive age worldwide. This review aimed to comprehensively examine the interplay between epigenetics and oxidative stress (OS) in the pathogenesis of EM. Through the integration of cutting-edge research, the response of OS signals to epigenetic modifications was explored. The microbiome exerts an influence on this causal regulatory relationship, and these mechanisms collectively contribute to the pathophysiology of EM. Specifically, this article highlighted the roles of epigenetics and OS in EM and underscored the importance of the microbiome as a regulatory link. A discussion was also held on the future directions of biomarkers and precision medicine, including the application prospects of epigenetic and OS markers in the diagnosis and treatment decision-making of EM, and innovations in therapeutic strategies like targeting epigenetic modifications and antioxidant therapies. Moreover, this review emphasized the potential of multi-omics integrated analysis to deepen the understanding of the disease, guide future therapeutic strategies and promote personalized medicine.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104462"},"PeriodicalIF":2.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487601","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}