Journal of Reproductive Immunology最新文献

{"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":"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}

{"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}