Journal of Reproductive Immunology最新文献

{"title":"Comparative analysis of oral, placental, and gut microbiota characteristics, functional features and microbial networks in healthy pregnant women","authors":"Guangyu Ma ,&nbsp;Ping Yang ,&nbsp;Tong Lu ,&nbsp;Xinyi Deng ,&nbsp;Lulu Meng ,&nbsp;Haishan Xie ,&nbsp;Juan Zhou ,&nbsp;Xiaomin Xiao ,&nbsp;Xiaomei Tang","doi":"10.1016/j.jri.2025.104535","DOIUrl":"10.1016/j.jri.2025.104535","url":null,"abstract":"<div><h3>Aim</h3><div>Most studies on pregnant women focus on analyzing individual microbial species at specific body sites. This study aims to explore the characteristics, functions, and microbial networks of the oral, placental, and gut microbiota in healthy pregnant women.</div></div><div><h3>Methods</h3><div>A total of 23 healthy pregnant women were enrolled in this study. We analyzed the microbial composition, functional profiles, and microbial networks of the oral, placental, and gut microbiota using 16S rRNA gene sequencing.</div></div><div><h3>Results</h3><div>Our findings revealed significant differences in microbial composition across these three sites. The placental microbiota contained a relatively high proportion of low-abundance microorganisms, which were more diverse and evenly distributed compared to the gut and oral microbiota. The microbial composition at each site displayed distinct characteristics, likely influenced by environmental, physiological, and biological factors. The placental microbiota exhibited a complex network of tightly interconnected genera, whereas the gut microbiota showed sparser connections, with fewer closely related genera compared to the placental and oral microbiota. Functional differences were also observed among the three microbiota, with each playing a unique role in maintaining host health and metabolic balance. While the oral and gut microbiota shared functional similarities, the placental microbiota exhibited distinct functional characteristics.</div></div><div><h3>Conclusions</h3><div>This study provides valuable insights into the microbial communities of healthy pregnant women, offering important data for microbiological research during pregnancy and laying the foundation for future investigations into the roles of these microbial communities in maternal health.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104535"},"PeriodicalIF":2.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891976","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":"An overview of the role of steroid hormones in various parasitic infections","authors":"Aftab Shaukat ,&nbsp;Muhammad Tahir Aleem ,&nbsp;Furqan Munir ,&nbsp;Fenfei Gao ,&nbsp;Ren-Wei Su","doi":"10.1016/j.jri.2025.104533","DOIUrl":"10.1016/j.jri.2025.104533","url":null,"abstract":"<div><div>There is a close relationship among hormones, neuropeptides, neurotransmitters, and cytokines that modify the host immune response through various effector mechanisms, including both humoral and cellular immunity. Interruption of this communication balance leads to infection or greater vulnerability to disease. The relationship between host and parasite is complex, and there is significant communication, interaction, and biochemical co-evolution. In parasitic infection, the role of various hormones has been proven and there are also reports on parasites the direct effect of hormones. Numerous parasites produce the secretion of molecules that affect the immunological and physiological responses in the host, including intermediaries and vectors. In contrast, the parasite secretes various factors that change the hormone host levels. In a few cases, the parasite's status hormones have negative and positive influences. On the other hand, the influences are indirectly intermediated through the host’s immune system. In vertebrates, the occurrence of parasites also has a main effect on the host endocrine status and a normal suite of processes ruled through hormones. This procedure comprises host growth, establishment, transformation, and reproduction. Therefore, considering the mechanism involved in immuno-endocrine variation and its influences on parasites is critical for emerging new drugs, vaccine target finding, and inventing new therapies for numerous infections. Males are usually more vulnerable to parasitic diseases as compared to females. These sex differentiation can reflect the suppressive properties of testosterone and the excessive effects of estradiol on immune function. For defining the T-cell-driven immunity <em>T. spiralis</em> infection is a perfect model and also provides the crucial visions that can affect potential helminths therapies currently in development. Conflicting host variables regulate the efficiency of such treatment and have recognized the host-derived sex steroid hormones as the main factor in the growth of immunity. This study categorized the role of circulating steroid hormones as an immune regulator in various parasitic diseases.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104533"},"PeriodicalIF":2.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860211","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 influence and association of blood on transfer catheter and vaginal microbiota on pregnancy outcomes in frozen-embryo transfer cycles","authors":"Li Fu ,&nbsp;Yingshun Zhou ,&nbsp;Ling Xu ,&nbsp;Yue O.O. Hu ,&nbsp;Shaowei Chen ,&nbsp;Mingyong Wang ,&nbsp;Xia Jiang ,&nbsp;Meiling Zheng ,&nbsp;Qiang Wu ,&nbsp;Junjiang Fu","doi":"10.1016/j.jri.2025.104530","DOIUrl":"10.1016/j.jri.2025.104530","url":null,"abstract":"<div><div>The effect of blood and mucus on the catheter on pregnancy outcomes in frozen-embryo transfer (FET) cycles remains relatively under-investigated. To evaluate the influence of the presence of blood and mucus on the transfer catheter, along with the characteristics of vaginal microbiota on pregnancy outcomes in FET cycles, we comprehensively analyzed the clinical data of 816 patients. We meticulously recorded the potential traces of blood and mucus on the catheter following embryo transfer (ET). We examined three key outcome parameters including implantation rate (IR), clinical pregnancy rate (CPR), and biochemical pregnancy rate (BPR). Our results demonstrated that the presence of blood on the catheter was associated with a marked decrease in BPR and CPR, whereas the presence of mucus had no significant impact on BPR, CPR, and IR. To further elucidate whether the influence of blood on the catheter on pregnancy outcomes was mediated by vaginal microbiota imbalance, we examined the vaginal microbiota using 16S rRNA gene sequencing and conducted in-depth statistical analyses and correlation studies. Interestingly, the alpha and beta diversity of the vaginal microbiota between the blood group and non-blood group differed significantly. Importantly, the abundance of <em>Lactobacillus</em> was markedly decreased in the blood group. Our results indicate that the negative effect of the blood on the catheter on pregnancy may be attributed to the imbalance of vaginal microbiota. These results provide new insights into the potential mechanisms underlying the association between vaginal microbiota and blood on the catheter and their impact on pregnancy outcomes in FET cycles.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104530"},"PeriodicalIF":2.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860210","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":"Rubia cordifolia Linn.: Isolation, Molecular Docking and BRAC1/PKD1 Gene Targeting for Polycystic Ovary Syndrome in Rats","authors":"Deepika Bhatia ,&nbsp;Diksha Sharma ,&nbsp;Kamal Shah ,&nbsp;Perwez Alam ,&nbsp;Hitesh Kumar Dewangan","doi":"10.1016/j.jri.2025.104532","DOIUrl":"10.1016/j.jri.2025.104532","url":null,"abstract":"<div><div>Polycystic Ovarian Syndrome (PCOS) is a disorder of endocrine system characterized by irregular menstrual cycles, high androgen levels, and polycystic ovaries. The aim of this study is to evaluate pharmacological activity of <em>Rubia cordifolia</em> (RC) in treating letrozole-induced PCOS in rats that exhibit metabolic and endocrinal criteria of PCOS patients. The plant RC was collected, characterized and prepared an extract, to obtained the phenolic and flavonoid content, which was confirmed by GC-MS. Obtained and confirmed content are proceeded for molecular docking and <em>in-vivo</em> study. The results of molecular docking found the favourable receptor<img>ligand interactions. and exhibited strong binding affinities (below -5 kcal/mol), The top-priority target genes were found to BRAC1, and PKD1. Further, <em>in-vivo</em> study was performed in female Wistar rats and PCOS was induced by oral administration of letrozole (1<!--> <!-->mg/kg, per orally, <em>p.o.</em>, 21-days). Due to PCOS significantly increases body-weight, ovarian weight/size, and cysts, while reduction in FSH level and fluctuation in glucose and LH levels. Then, rats were treated with different dose of RC extract (100/200/400<!--> <!-->mg/kg/day, <em>p.o.</em>), and metformin take as standard (20<!--> <!-->mg/kg/day, <em>p.o.</em>). Resulted in a significantly decrease body-weight, ovarian weight/size, maintain glucose and hormones level. Additionally, histological analysis of rat ovaries revealed a fewer cyst in treated group compared to the untreated group. All of these effects were significantly reduced by RC administration. Our results proved that RC ameliorates letrozole-induced PCOS.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104532"},"PeriodicalIF":2.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816768","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":"Comprehensive analysis of alterations in spermatogenic stages after immunization with lactate dehydrogenase-C in male albino rats","authors":"Harpreet Kaur,&nbsp;Nisha Vashishat","doi":"10.1016/j.jri.2025.104531","DOIUrl":"10.1016/j.jri.2025.104531","url":null,"abstract":"<div><div>The ever-rising global population emphasizes on requirement for the development of new contraceptive techniques that fits the needs and preferences of people during their reproductive phases of life. Immunocontraception is the process of inducing a humoral immune response by using a reproductive protein that renders a sperm infertile for a predetermined amount of time. One of the reproductive proteins found on the sperm membrane that is known to have immunogenic qualities is lactate dehydrogenase-C (LDH-C). The present study was planned to assess the effect of LDH-C as an immunocontraceptive agent in male albino rats. Sperm membrane extract (SME) was prepared using deoxycholate detergent. Proteins from the SME were separated on reducing SDS-PAGE, further fractioned by gel filtration chromatography on sephadex G-25 to isolate LDH-C proteins. Rats were immunized with purified LDH-C for a period of 28 days at weekly intervals. ELISA confirmed the presence of antibodies as a high antibody titre of 6400 was observed on 35 DPI that remained consistent till 77 DPI, and then declined afterwards. Fertility rate decreased by 85.70 % in immunized male rats. It can be concluded from the study that LDH-C antigens are capable of eliciting reversible immune response, significantly affecting the sperm motility amongst various sperm parameters and histological results have revealed that the effect of immunization was at testicular level as the total number of spermatogenic cells decreased in immunized rats making it a potential candidate for immunocontraceptive vaccines.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104531"},"PeriodicalIF":2.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808122","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":"Association between the dietary index for gut microbiota and female infertility: The mediation effects of lymphocyte count and red blood cell folate","authors":"Qingwen He ,&nbsp;Yangkun Feng ,&nbsp;Yun Zhang ,&nbsp;Mengyuan Lin","doi":"10.1016/j.jri.2025.104528","DOIUrl":"10.1016/j.jri.2025.104528","url":null,"abstract":"<div><div>Previous studies have revealed a the relationship between changes in the gut microbiota composition and female infertility. While the association between the dietary index for gut microbiota (DI-GM) and female infertility remains unstudied. The correlation was investigated with NHANES data from 2013 to 2018, with dietary recall data being used to calculate the DI-GM. Mediation analysis was performed to explore the role of lymphocyte count (LC) and red blood cell (RBC) folate in the DI-GM-induced risk of female infertility risk. Among the 1555 individuals included in our study, 311 were diagnosed with female infertility. According to the weighted binary logistic regression analyses, when all the covariates were adjusted, a negative association was observed between the DI-GM score and the risk of female infertility (OR: 0.80, 95 %CI: 0.74–0.88). After grouping participants by DI-GM score, compared with scores in the lowest quartile (Q1), the scores in Q3 and Q4 of DI-GM score were negatively associated with female infertility in crude and adjusted models, with ORs (95 %CI; P for trend) of 0.44 (0.27–0.70; &lt;0.001); 0.43 (0.28–0.64; &lt;0.001) and 0.43(0.26–0.71; &lt;0.001); 0.41(0.27–0.60; &lt;0.001). Additionally, restricted cubic splines logistic analysis uncovered a nonlinear association between the DI-GM score and the prevalence of female infertility. Mediation analysis indicated that LC and RBC folate mediated 4.64 % and 7.08 %, respectively of the association of the DI-GM scores with risk of female infertility. The nomogram exhibited good performance in this study (AUC 0.70, 95 % CI = 0.67–0.73). Our research revealed that the DI-GM score was negatively related to risk of female infertility. Mediation analyses demonstrated that LC and RBC folate levels significantly mediate the association between the DI-GM and the prevalence of female infertility.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104528"},"PeriodicalIF":2.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799150","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 reveals causal associations between plasma metabolites, immune cell phenotypes, and ovarian hyperstimulation syndrome","authors":"Shanshan Chen ,&nbsp;Bo Yao ,&nbsp;Yanting Wang ,&nbsp;Jing Wang ,&nbsp;Ying Gu ,&nbsp;Xuanyi Chen","doi":"10.1016/j.jri.2025.104529","DOIUrl":"10.1016/j.jri.2025.104529","url":null,"abstract":"<div><div>In this study, we employed Mendelian randomization (MR) analysis to explore the causal relationships between immune cell phenotypes, plasma metabolites, and ovarian hyperstimulation syndrome (OHSS). Through the analysis of 731 immune cell phenotypes and 1400 plasma metabolites, we identified 32 immune cell phenotypes that are causally related to OHSS, with 18 phenotypes identified as protective and 14 as risk factors. Notably, the TCRgd AC phenotype was the most significant risk factor associated with OHSS. Our findings also revealed that among the 10 plasma metabolites causally linked to OHSS, three acted as protective factors, while seven were identified as risk factors. The Alpha-ketoglutarate to alanine ratio stood out as the most significant protective metabolite. Further investigation established a causal link between the EM DN (CD4-CD8-) AC immune cell phenotype and the Alpha-ketoglutarate to alanine ratio. Reverse MR analysis indicated that OHSS influences the expression of HLA-DR on myeloid OC cells. Mediation analysis suggested a non-significant mediation effect of the Alpha-ketoglutarate to alanine ratio in the pathway from immune cells to OHSS, accounting for −8.68 % of the total effect. Collectively, our results underscore the role of specific immune cell phenotypes and plasma metabolites in the pathogenesis of OHSS, revealing potential targets for developing interventions aimed at reducing the risk of OHSS.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104529"},"PeriodicalIF":2.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816769","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":"Mitochondrial genetic landscape and its correlation with immune cell infiltration in preeclampsia: Insights from bioinformatics","authors":"Xunjia Ye ,&nbsp;Jieying Yu ,&nbsp;Youyuan Zhuo ,&nbsp;Anlu Yong ,&nbsp;Jiachun Wei ,&nbsp;Ruiman Li ,&nbsp;Shuo Wan ,&nbsp;Guang Wang ,&nbsp;Xuesong Yang","doi":"10.1016/j.jri.2025.104527","DOIUrl":"10.1016/j.jri.2025.104527","url":null,"abstract":"<div><h3>Background</h3><div>Preeclampsia (PE), a hypertensive pregnancy disorder, remains a leading cause of maternal and perinatal morbidity and mortality. Mitochondria-related placental metabolic dysfunction is implicated in PE, but its mechanistic role is unclear. This study aimed to identify mitochondria-related genes (MRGs) and their possible regulatory mechanisms in PE.</div></div><div><h3>Methods</h3><div>Differentially expressed mitochondria-related genes (MRGs) of PE were identified from Gene Expression Omnibus (GEO) dataset GSE114691 and GSE190971. LASSO regression analysis was used to screen key MRGs. Datasets GSE75010 and GSE25906 were used to validate the efficiency of the MRGs predictive model via receiver operating characteristic (ROC) curve analysis. Gene set enrichment analysis (GSEA) was conducted to verify underlying biological pathways in PE. Furthermore, we investigated the correlation analysis of MRGs and immune cell infiltration, as well as the association between the MRGs and clinical features. Single-cell sequencing analysis and immunofluorescence staining were used to verify the expression of critical gene in the placenta.</div></div><div><h3>Results</h3><div>Five hub MRGs (<em>MOCS1</em>, <em>CYP11A1</em>, <em>GATM</em>, <em>SFXN3</em>, and <em>BCL2L11</em>) showed high diagnostic accuracy for PE and correlated with immune cell infiltration. <em>CYP11A1</em> was further associated with Hemolysis, Elevated Liver enzymes, Low platelets (HELLP) syndrome and predominantly expressed in extravillous trophoblasts, with upregulated expression in PE placenta.</div></div><div><h3>Conclusion</h3><div>The interaction between MRGs with the immune microenvironment might be vital in the development of PE. Among 5 hub MRGs, CYP11A1 might be a potential biomarker of HELLP syndrome. These findings provide novel insights into the underlying pathophysiology of PE and the discovery of new therapeutic targets.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104527"},"PeriodicalIF":2.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792516","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":"PPAR-gamma agonist pioglitazone improves endometrial receptivity, reverses endometrial barrier disruption and promotes ovarian function in thin endometrium rats via modulation PPAR-γ/Wnt5/β-catenin pathway","authors":"Heqiao Li ,&nbsp;Yu Guan ,&nbsp;Xinru Chen ,&nbsp;Wenfan Tian ,&nbsp;Jinghong Xie ,&nbsp;Bin Yang","doi":"10.1016/j.jri.2025.104526","DOIUrl":"10.1016/j.jri.2025.104526","url":null,"abstract":"<div><div>Thin endometrium (TE) is a common reproductive endocrine disorder, PPAR-γ has been reported to regulate cell proliferation and crosstalk with the Wnt5/β-catenin pathway. However, whether PPAR-γ promotes endometrial epithelial cell proliferation and acts through the Wnt5/β-catenin pathway has not been explored. A rat model of endometrial thinning was established and administered for 15 days, and the morphology of the uterus and ovaries was observed by HE staining. Serum sex hormone levels were measured by enzyme-linked immunosorbent assay (ELISA). The morphology of endometrial surface was observed by electron microscopy. Immunohistochemistry was used to detect the expression of endometrial receptivity, endometrial barrier and ovarian function proteins. Activation of PPAR-γ/Wnt5/β-catenin pathway was analyzed by molecular docking and Western blotting. The results showed that PIO improved endometrial morphology, endometrial thickness, gland number and expression of endometrial tolerance-related proteins, and promoted the repair of endometrial barrier in TE rats. Serum hormone levels, mature follicle and corpus luteum numbers were increased, indicating improved ovarian function. PIO downregulated the Wnt5/β-catenin signaling pathway and increased the expression of ovarian endocrine-related proteins, as shown by western blot analysis. Our findings revealed that thr PPAR-γ agonist pioglitazone inhibited the Wnt5/β-catenin pathway by up-regulating the expression of PPAR-γ and promoted the proliferation of epithelial cells and the repair of the endometrial barrier, which played a role in protecting ovarian function while treating TE.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104526"},"PeriodicalIF":2.9,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768408","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":"Measurement of four novel endometrial NK cell subsets by multiplex staining in women with reproductive failure: A comparison with fertile controls","authors":"Lu Chen ,&nbsp;Wen-Jui Yang ,&nbsp;Xiaoyan Chen ,&nbsp;Joshua Jing Xi Li ,&nbsp;Qianhan Xu ,&nbsp;Jun Chen ,&nbsp;Chi Chiu Wang ,&nbsp;Jacqueline Pui Wah Chung ,&nbsp;Mingqing Li ,&nbsp;Tin Chiu Li ,&nbsp;Tao Zhang","doi":"10.1016/j.jri.2025.104525","DOIUrl":"10.1016/j.jri.2025.104525","url":null,"abstract":"<div><div>Accumulating evidence indicates a significant increase in CD56 + endometrial NK cells in women with reproductive failure. However, CD56 alone inadequately captures the phenotypic and functional heterogeneity of these cells. This study aims to compare the density of various endometrial NK subsets between women with reproductive failure and healthy controls, as well as evaluate their diagnostic performance. This study included three groups: recurrent miscarriage (RM), repeated implantation failure (RIF), and controls, with 56 women in each group. Endometrial biopsy was performed precisely 7 days after LH surge or five days after the initiation of progesterone. Multiplex immunohistochemistry staining was employed to identify total CD56 +NK cells, classical NK subsets (CD56 +CD16 + and CD56 +CD16-), and four novel NK subsets: NK1-NK4. Using classical markers of NK cells, the density of CD56 +NK cells, as well as CD56 +CD16 + and CD56 +CD16- NK subsets, was significantly higher in women with RM or RIF compared to controls. When NK cells were further categorized into 4 subsets, only the immune-active NK2 and cytotoxic NK4 subsets showed a significant increase in women with RM or RIF groups. No significant differences were observed in the densities of NK1 and NK3. CD56 +CD16 + NK cells, NK2 and NK4 subsets demonstrated higher diagnostic accuracy over total CD56 + NK cells, as indicated by ROC analysis. In summary, this study reveals the specific differences in endometrial NK cell subsets in women with reproductive failure, suggesting that the elevated density of certain NK subsets in the endometrium is associated with an inflammatory microenvironment in women with reproductive failure.</div></div>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"169 ","pages":"Article 104525"},"PeriodicalIF":2.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777642","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}