Journal of Reproductive Immunology最新文献

{"title":"Corrigendum to \"The role of reproductive tract microbiota in gynecological health and diseases\" [J. Reprod. Immunol. 167 (2025) 104418].","authors":"Nanzhu Wang, Liyu Zhang, Xin Liu, Lan Xu","doi":"10.1016/j.jri.2026.104899","DOIUrl":"https://doi.org/10.1016/j.jri.2026.104899","url":null,"abstract":"","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":" ","pages":"104899"},"PeriodicalIF":2.9,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774818","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 metabolism of arachidonic acid and diseases during pregnancy.","authors":"Mengjiao Kuang, Fei Fu, Menghua Kuang, Xiaoyu Yu","doi":"10.1016/j.jri.2026.104889","DOIUrl":"https://doi.org/10.1016/j.jri.2026.104889","url":null,"abstract":"<p><p>Arachidonic acid (AA) is an essential polyunsaturated fatty acid in humans and a key component of the phospholipid bilayer in cell membranes. Under various stimuli, AA is released from phospholipids; however, elevated levels of AA can act as inflammatory mediators, triggering inflammatory responses. During pregnancy, the placenta synthesizes large amounts of AA to play a critical role in fetal development, preparation for childbirth, and maternal-fetal adaptation. Here, we systematically review the biological mechanisms of AA during pregnancy and its potential involvement in related disorders. We aim to comprehensively elucidate the correlation between AA levels and both physiological and pathological changes during pregnancy. Our findings provide novel theoretical insights and potential therapeutic targets for the prevention and treatment of pregnancy-related complications. These research advances contribute to a deeper understanding of the pathogenesis of pregnancy-associated diseases and offer important scientific support for ensuring maternal and fetal health and safety.</p>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":" ","pages":"104889"},"PeriodicalIF":2.9,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633727","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":"Gut microbiota and pattern recognition receptors in polycystic ovary syndrome.","authors":"Jintao Yuan, Shiqiong Sun, Essam H Ibrahim, Muhammad Azhar Ud Din, Fei Mao, Suping Du","doi":"10.1016/j.jri.2026.104882","DOIUrl":"https://doi.org/10.1016/j.jri.2026.104882","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is increasingly recognized as a disorder of impaired immune-endocrine homeostasis. Emerging evidence indicates that intestinal dysbiosis and microbial metabolite imbalance can activate pattern recognition receptors (PRRs), forming a PRR microbiota reproductive axis that contributes to PCOS pathophysiology. This review synthesizes current insights into how gut-derived signals, including LPS, peptidoglycans, SCFAs, bile acids, and tryptophan metabolites, modulate TLR-, NLR-, and RLR-mediated pathways to disrupt ovarian, endometrial, and systemic immune regulation. We further propose a unifying framework, the Reproductive Immune Tolerance Disruption Theory, which posits that chronic PRR activation shifts reproductive tract immunity from a tolerogenic to a low-grade inflammatory state, thereby promoting hyperandrogenism, anovulation, insulin resistance, and metabolic dysfunction. We also summarize recent multi-omics and immunometabolic studies that clarify the crosstalk between gut microbial signatures and innate immune signaling. Finally, we highlight precision strategies, including PRR-selective immunomodulation, microbiota-based therapies, and epigenetic metabolic interventions that hold translational potential for redefining PCOS management. Understanding PRR-driven microbial immunomodulation provides a mechanistic framework for reconciling endocrine, metabolic, and reproductive abnormalities in PCOS, guiding the development of targeted therapeutic approaches.</p>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":" ","pages":"104882"},"PeriodicalIF":2.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147619036","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":"Corrigendum to \"Increasing expression of STING by ERα antagonizes LCN2 downregulation during chronic endometritis\" [J. Reprod. Immunol. 160 (2023) 104167].","authors":"Min Chu, Shunzhi He, Huishan Zhao, Shuyuan Yin, Zhenteng Liu, Wei Zhang, Xuemei Liu, Hongchu Bao","doi":"10.1016/j.jri.2026.104881","DOIUrl":"https://doi.org/10.1016/j.jri.2026.104881","url":null,"abstract":"","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":" ","pages":"104881"},"PeriodicalIF":2.9,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574634","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":"Immunomodulation of peripheral blood NK cells by sialic acid expressed on syncytialized BeWo cells","authors":"Juan C. Quintana-Castillo ,&nbsp;Vásquez-Escobar Paola ,&nbsp;Buitrago-Orozco Lizeth ,&nbsp;Escobar-Paredes Axel ,&nbsp;Daniela Villota-Luna ,&nbsp;Julio Bueno-Sánchez","doi":"10.1016/j.jri.2026.104848","DOIUrl":"10.1016/j.jri.2026.104848","url":null,"abstract":"<div><div>Preeclampsia (PE) is characterized by placental dysfunction and a systemic inflammatory state. This study investigated how hypoxia-inducible factor (HIF)-driven changes in sialic acid expression on syncytialized BeWo cells. Then we study the sialic acid modulation of peripheral natural killer (pNK) cell activity. Using a syncytialized BeWo cell model, chemical hypoxia was induced with DMOG to stabilize HIF-1α/HIF-2α. This HIF activation significantly reduced the expression of terminal mannose, α-2,3- and α-2,6-linked sialic acid. In a Co-culture syncytialized BeWo cells suppressed IFN-ɣ production in pNK cells, an effect most pronounced in the immunoregulatory CD56bright subset. Furthermore, this suppression was reversed by enzymatic removal of sialic acid (sialidase treatment), confirming its direct inhibitory role. Paradoxically, proinflammatory cytokines such as TNF-α or serum from PE patients significantly increased sialic acid expression on syncytialized BeWo cells. In parallel, soluble sialic acid directly stimulated IFN-ɣ production in pNK cells. Our in vitro findings lead us to propose a model in which HIF-driven sialic acid loss on the syncytiotrophoblast may represent a novel mechanism contributing to maternal immune activation in preeclampsia. This hypothesized pathway could potentially link placental isquemia/reperfusion to NK cell activation and systemic inflammation.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"174 ","pages":"Article 104848"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202019","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":"Placental ferroptosis in preeclampsia: An integrative and comprehensive review","authors":"Tamir Edri,&nbsp;Sapir Lianski,&nbsp;Sarah M. Cohen,&nbsp;Ofer Beharier","doi":"10.1016/j.jri.2026.104863","DOIUrl":"10.1016/j.jri.2026.104863","url":null,"abstract":"<div><div>Ferroptosis, a regulated form of iron-dependent cell death driven by lipid peroxidation, has recently gained attention as a potential contributor to the pathophysiology of preeclampsia, a major cause of maternal and perinatal morbidity and mortality. This review synthesizes current evidence linking ferroptosis to placental dysfunction and explores its relevance to the pathogenesis of preeclampsia. We examine how disrupted iron metabolism, oxidative stress, and impaired antioxidant defenses create a permissive environment for ferroptotic damage in the syncytiotrophoblast. Key biochemical pathways, including redox phospholipid metabolism, glutathione-GPX4 activity, and mitochondrial function, are reviewed in detail. We also discuss emerging data connecting placental ferroptosis to systemic maternal manifestations via sFlt-1 release and extracellular vesicle-mediated endothelial injury. Finally, we highlight therapeutic implications, including pharmacological inhibition of ferroptosis and drug repurposing strategies. By integrating diverse mechanistic insights, ferroptosis emerges as a unifying paradigm that may reshape our understanding and treatment of preeclampsia.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"174 ","pages":"Article 104863"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776179","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":"Vδ2 T-cell cytotoxic polarity shift is associated with vascular dysfunction in unexplained recurrent miscarriage: A preliminary study","authors":"Xiao-xia He ,&nbsp;Hong-xing Li ,&nbsp;Yi Jin ,&nbsp;Xi Xi ,&nbsp;Xiao-ling Ma ,&nbsp;Ya-ming Xi","doi":"10.1016/j.jri.2026.104861","DOIUrl":"10.1016/j.jri.2026.104861","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the link between the cytotoxic profiles of peripheral blood Vδ2 γδT cells and vascular injury in unexplained recurrent miscarriage (URM)</div></div><div><h3>Methods</h3><div>A total of 30 URM patients and 30 matched healthy controls were enrolled. Using flow cytometry, we analyzed γδT and Vδ2 subsets, and their expression of perforin and granzyme B. Serum levels of vascular injury markers (sFlt-1, sEng, vWF, LDH, VCAM-1) were measured by ELISA.</div></div><div><h3>Results</h3><div>While no significant differences were observed in the total proportion of γδT cells or in IL-22 expression, URM patients exhibited a marked cytotoxic polarization within the Vδ2 subset: the frequency of Granzyme B⁺Perforin⁺ (GB⁺PF⁺) Vδ2 cells was significantly elevated, whereas GB⁺PF⁻ cells among total γδT and Vδ2 populations were significantly decreased. Concordantly, serum levels of sFlt-1 and vWF were significantly elevated in the URM group, with a trend toward lower sEng. LDH and VCAM-1 did not differ between groups. Importantly, correlation analysis revealed distinct immune–vascular association patterns: sFlt-1 levels were positively correlated with the proportions of GB⁺PF⁻ CD3⁺ and GB⁺PF⁻ γδT cells, whereas vWF levels showed a negative correlation with GB⁺PF⁻ γδT cells but a positive correlation with GB⁺PF⁺ Vδ2 cells.</div></div><div><h3>Conclusion</h3><div>This study provides preliminary evidence for a cytotoxic polarization of Vδ2 cells in URM, which appears to be associated with markers of vascular injury. These findings identify a potential association between perforin-expressing Vδ2 cells and URM pathogenesis, highlight a novel putative immuno-vascular interaction, and offer hypothesis-generating insights for future investigative and therapeutic strategies.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"174 ","pages":"Article 104861"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306871","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":"Trends and frontiers of tumor necrosis factor in research in endometriosis: A comprehensive bibliometric analysis","authors":"Qunhuan Huang,&nbsp;Jing Chen,&nbsp;Hong Yang,&nbsp;Yiting Wan,&nbsp;Xiaoling Ma,&nbsp;Yanhua Song","doi":"10.1016/j.jri.2026.104859","DOIUrl":"10.1016/j.jri.2026.104859","url":null,"abstract":"<div><h3>Background</h3><div>Tumor necrosis factor (TNF) plays a prominent role in endometriosis research, but the evolution and current status of this field have not been systematically mapped.</div></div><div><h3>Methods</h3><div>This bibliometric study systematically analyzed publications on TNF and endometriosis indexed in the Web of Science Core Collection from 1988 to 2024. Bibliometric visualization and analysis were conducted using VOSviewer, CiteSpace, and the R package “bibliometrix.”</div></div><div><h3>Results</h3><div>A total of 645 publications were identified. China was the most prolific country (138 publications), followed by the USA (105) and Japan (78). Leading institutions included Harvard University and Fudan University. Major journals such as <em>Fertility and Sterility</em> and <em>Human Reproduction</em> served as primary publication venues. Notable authors included Yutaka Osuga, Akoum A, and Miyuki Harada. Analysis revealed six main research clusters: \"Disease Mechanisms,\" \"Cellular Pathways,\" \"Immune Response,\" \"Genetic and Molecular Factors,\" \"Experimental Models and Biomarkers,\" and \"Reproductive Outcomes.\" Keyword burst analysis indicated evolving research priorities, with recent focus on inflammation, oxidative stress, and pathogenesis.</div></div><div><h3>Conclusions</h3><div>This bibliometric analysis maps the intellectual structure and thematic evolution of TNF-related endometriosis research, highlighting major contributors, influential journals, and emerging hotspots. The findings provide a reference framework to inform future research directions and support the identification of trends and gaps within this evolving field.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"174 ","pages":"Article 104859"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202057","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":"Pathologic abnormalities of deep placentation in the great obstetrical syndromes: Implications for understanding the pathophysiology, risk assessment in early pregnancy, and personalized prevention","authors":"Gergő Leipold ,&nbsp;Roberto Romero ,&nbsp;Pierre-Yves Robillard ,&nbsp;Petra Merkely ,&nbsp;Máté Posta ,&nbsp;Gábor Szalai ,&nbsp;Zsófia Benkő ,&nbsp;Tamás Marton ,&nbsp;Sándor Valent ,&nbsp;Adi L. Tarca ,&nbsp;Beáta Hargitai ,&nbsp;Sándor Nagy ,&nbsp;Zoltán Papp ,&nbsp;Offer Erez ,&nbsp;Nándor Ács ,&nbsp;Nándor Gábor Than","doi":"10.1016/j.jri.2026.104846","DOIUrl":"10.1016/j.jri.2026.104846","url":null,"abstract":"<div><div>The concept of the <em>Great Obstetrical Syndromes</em> was introduced to explain the unique nature of obstetrical disease, which differs fundamentally from disorders in other areas of medicine. These syndromes, including preeclampsia, fetal growth restriction, fetal death, and spontaneous preterm birth, represent clinical endpoints rather than single diseases and share defining characteristics: they arise from multiple etiologies, have a prolonged subclinical phase, involve the fetus as an active participant, are adaptive in nature, and result from complex genetic and environmental interactions between the mother and fetus. Among the diverse mechanisms leading to these syndromes, abnormalities of the maternal supply line to the placenta constitute one major etiology and are often caused by vascular disorders affecting the maternal cardiovascular system and uterine spiral arteries, resulting in placental lesions of maternal vascular malperfusion. The most severe spiral artery lesion is atherosis, which closely resembles atherosclerosis and links obstetrical syndromes to maternal vascular disease. Disorders of deep placentation associated with maternal vascular malperfusion are accompanied by characteristic alterations in angiogenic balance, and the ratio of placental growth factor to soluble fms-like tyrosine kinase-1 in the maternal circulation serves as a biomarker of this pathophysiologic process. Importantly, each obstetrical syndrome is associated with a stereotypic temporal pattern of angiogenic imbalance that reflects differences in disease burden, timing, and clinical expression. While substantial progress has been made in the prediction and prevention of preeclampsia, these concepts extend to other obstetrical syndromes, including fetal growth restriction, fetal death, and spontaneous preterm labor, supporting a unified biologic framework for early risk assessment and personalized prevention.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"174 ","pages":"Article 104846"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306090","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":"Interleukin-33 at the maternal-fetal interface: From immune tolerance to obstetric syndromes","authors":"Tao Liu ,&nbsp;Haiqing Huang ,&nbsp;Hui Yin","doi":"10.1016/j.jri.2026.104855","DOIUrl":"10.1016/j.jri.2026.104855","url":null,"abstract":"<div><div>Successful viviparous reproduction depends on a finely tuned state of maternal–fetal immune tolerance. Among the mediators that shape this balance, the alarmin cytokine interleukin-33 (IL-33) has drawn growing attention as a key regulatory checkpoint. Here, we bring together recent findings to interpret IL-33 function through a “Two-Wave” framework that helps reconcile its seemingly opposing roles in pregnancy. In early gestation, a controlled, spatially confined release of IL-33 appears essential for processes such as decidualization, spiral artery remodeling, and the establishment of a Type 2–biased immune environment. These effects are largely mediated through group 2 innate lymphoid cells, regulatory T cells, and M2 macrophages, which collectively sustain a tolerogenic interface. Later in pregnancy, however, an abrupt or excessive surge of IL-33—often in response to infection or tissue injury—can provoke intense inflammation. Such is now recognized as a shared pathological feature in major obstetric syndromes. In preeclampsia, excess sST2 neutralizes IL-33 activity, creating a state of functional deficiency, whereas in preterm birth, IL-33 released from fetal membranes may act as a trigger for premature labor. Given its pivotal position at the intersection of immune tolerance and inflammation, the IL-33/ST2 pathway offers both mechanistic insight and promising opportunities for biomarker development and targeted immunotherapy in complicated pregnancies.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"174 ","pages":"Article 104855"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157545","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}