Journal of Reproductive Immunology最新文献

{"title":"Peri-implantation treatment with TNF-α inhibitor for endometriosis and/or adenomyosis women undergoing frozen-thawed embryo transfer: A retrospective cohort study.","authors":"Mengqi Liu, Yan Li, Yuan Yuan, Min Jiang, Ping Yin, Dongzi Yang","doi":"10.1016/j.jri.2024.104415","DOIUrl":"10.1016/j.jri.2024.104415","url":null,"abstract":"<p><strong>Problem: </strong>Endometriosis and adenomyosis have common pathogenesis and close relationship, with multi-factors involved in related infertility and IVF failure. They lead to anatomical changes, ovarian reserve reduction, endocrine abnormalities, altered endometrial receptivity and immunological dysfunction. Collective evidence indicate that abnormal function of immune cells and secretion of cytokines are closely related to reproductive outcomes among the women. Some studies showed that increased secretion of tumor necrosis factor alpha (TNF-α) led a key role in pro-inflammatory response in women with endometriosis/adenomyosis.TNF-a is embrryotoxic and receptivity impairing. Therefore, immunotherapy is a targeted therapeutic strategy apart from routine treatment. TNF-α inhibitors such as etanercept and adalimumab were shown to reduce the embryotoxic and anti-inflammatory effects to increase IVF pregnancy rates in recurrent implantation failure or endometrioma patient. However, there's no evidence about the use of adalimumab for patients with endometriosis and/or adenomyosis undergoing Frozen embryo transfer(FET).</p><p><strong>Method of study: </strong>A retrospective analysis of 141 women with endometriosis and/or adenomyosis undergoing FET from January 2021 to Jun 2023 was conducted.They were 20-42 years old, with or without previous implantation failure. Endometriosis was diagnosed by laparoscopy during their infertility workup and adenomyosis was confirmed by vaginal ultrasound screening. GnRH agonist and hormone replacement treatment (HRT) or HRT were taken for endometrium preparation according to doctor's evaluation and preference. Before and after embryo transfer, 84 women were treated with Adalimumab and 57 patients were untreated. Implantation rate, clinical pregnancy rate, ongoing pregnancy rate and live birth rate were compared between the two groups.</p><p><strong>Results: </strong>The demographics and baseline characteristics between the two groups were comparable. Stage of embryo transferred and number of embryo transferred were comparable between the two groups (p = 0.227 and p = 0.204 separately). The regimen of endometrium preparation was similar too(p = 0.907). The implantation rate was significantly improved in study group (28.09 % vs 49.18 %, X<sup>2</sup>=9.515, P = 0.002). The clinical pregnancy rate was much lower in control group comparing with TNF-α inhibitor treatment group (42.11 % vs 60.71 %, X<sup>2</sup>=4.723, P = 0.029). There was no significant difference between the two groups as for ongoing pregnancy rate (38.60 % vs 52.38 %, X<sup>2</sup>=2.591, P = 0.107)and live birth rate (36.84 % vs 47.62 %, X<sup>2</sup>=1.606, P = 0.205). Following adjustment for age, BMI, number of prior failed transfer, stage of embryo transferred in a multiple logistic analysis, patients treated without TNF-α inhibitor had a significant lower CPR (ORadj 0.45, 95 %CI 0.22-0.92, p = 0.029) and a similar probability for OPR ","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"104415"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864634","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":"Active immunization against gonadotropin-releasing hormone enhances the generation of B cells but does not affect their colonization in peripheral immune organs in male rats.","authors":"Dong Li, Huan Yao, Xiaohan Cao, Xingfa Han, Tianzeng Song, Xianyin Zeng","doi":"10.1016/j.jri.2024.104402","DOIUrl":"10.1016/j.jri.2024.104402","url":null,"abstract":"<p><p>Active immunization against gonadotropin-releasing hormone (GnRH) affects the immune system by inhibiting testosterone production. Our previous study investigated the effects of GnRH immunization on thymic T-cell generation, migration, and colonization in peripheral immune organs. However, the mechanisms by which GnRH immunization influences B cell generation and the characteristics of B cell colonization in peripheral immune organs remain unclear. Herein, GnRH immunization enhanced B cell generation by reducing apoptosis. GnRH immunization did not markedly affect the cell cycle of bone marrow cells, B cell development-related signaling molecules, or the percentage of B cells in the blood, spleen, or inguinal lymph nodes. After testosterone supplementation in GnRH-immunocastrated rats, the generation of B cells in the bone marrow was significantly reduced, and the apoptosis of B cells was remarkably increased. Testosterone did not significantly affect the cell cycle of bone marrow cells or the proportion of B cells in the blood, spleen, or inguinal lymph nodes of the GnRH-immunocastrated rats. Overall, these results clarify the mechanisms related to B cell expansion in the bone marrow and the settlement characteristics of B cells in peripheral immune organs after GnRH immunization.</p>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"104402"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786001","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":"Efferocytosis and infertility: Implications for diagnosis and therapy.","authors":"Sareh Bakhshandeh Bavarsad, Soroosh Shahryarhesami, Noorodin Karami, Nasim Naseri, Amir Tajbakhsh, Seyed Mohammad Gheibihayat","doi":"10.1016/j.jri.2024.104413","DOIUrl":"10.1016/j.jri.2024.104413","url":null,"abstract":"<p><p>Recent research has shed light on the intricate connection between efferocytosis and infertility, revealing its dysregulation as a contributing factor in various reproductive diseases. Despite the multifaceted nature of infertility etiology, the impact of insufficient clearance of apoptotic cells on fertility has emerged as a focal point. Notably, the removal of apoptotic cells through phagocytosis in the female reproductive system has been a subject of extensive investigation in the field of infertility. Additionally, special functions performed by immune system cell types, such as macrophages and Sertoli cells, in the male reproductive system underscore their significance in spermatogenesis and the efferocytosis of apoptotic germ cells. Dysregulation of efferocytosis emerges as a critical factor contributing to reproductive challenges, such as low pregnancy rates, miscarriages, and implantation failures. Moreover, defective efferocytosis can lead to compromised implantation, recurrent miscarriages, and unsuccessful assisted reproductive procedures. This review article aims to provide a comprehensive overview of efferocytosis in the context of infertility. Molecular mechanisms underlying efferocytosis, its relevance in both female and male infertility, and its implications in various reproductive diseases are elucidated. The elucidation of the intricate relationship between efferocytosis and infertility not only facilitates diagnosis but also paves the way for targeted therapeutic interventions.</p>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"104413"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779982","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 reproductive tract microbiota in gynecological health and diseases.","authors":"Zhunan Wang, Liyu Zhang, Xin Liu, Lan Xu","doi":"10.1016/j.jri.2024.104418","DOIUrl":"10.1016/j.jri.2024.104418","url":null,"abstract":"<p><p>The reproductive tract, as a lumen connected to the outside world, its microbial community is influenced by various factors. The changes in its microbiome are closely related to women's health. The destruction of the micro ecological environment will lead to various infections, such as Bacterial vaginosis, sexually transmitted infections, adverse pregnancy outcomes, infertility and tumors. In recent years, with the continuous development and progress of molecular biology, research on reproductive tract microbiota has become a clinical hotspot. The reproductive tract microbiota is closely related to the occurrence and development of female reproductive tract diseases such as vaginitis, pelvic inflammation, PCOS, cervical lesions, and malignant tumors. This article reviews the research on the relationship between vaginal microbiota and female reproductive tract diseases, in order to provide theoretical basis for the prevention and treatment of female reproductive tract diseases.</p>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"104418"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864637","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":"Enhanced capture of preeclampsia-derived extracellular vesicles from maternal plasma by monocytes and T lymphocytes.","authors":"Hephzibah E Winter, José M Murrieta-Coxca, Daniel Álvarez, Julián Henao-Restrepo, Paulina Fuentes-Zacarías, Sebastian Arcila-Barrera, Frank Steiniger, Tanja Groten, Udo R Markert, Diana M Morales-Prieto","doi":"10.1016/j.jri.2024.104417","DOIUrl":"10.1016/j.jri.2024.104417","url":null,"abstract":"<p><p>Released from trophoblast and other fetal cells, placental extracellular vesicles (EVs) reach the maternal peripheral blood and modulate immune responses. Increased EVs in plasma of preeclampsia (PE) patients indicate their involvement in the etiology of this condition. This study addresses the uptake of plasma EVs by peripheral blood mononuclear cells (PBMCs) and explores the underlying internalization mechanisms. Plasma EVs were isolated from women with normotensive pregnancy (EV_NP) and those with PE (EV_PE), and characterized by cryo-transmission electron microscopy, nanoparticle tracking analysis, Western blotting, flow cytometry, and micro bicinchoninic acid assay (micro-BCA). To investigate whether the origin of PBMCs affects uptake, samples from males, pregnant women, and non-pregnant women were included. Primary PBMCs and macrophages derived from the human leukemia monocytic cell line THP-1 were incubated with PKH-stained EVs, and uptake was assessed by flow cytometry and confocal microscopy. Key molecules involved in monocyte differentiation and macrophage function were evaluated in EV-treated cells using LEGENDplex™ assay and real-time polymerase chain reaction (RT-PCR). Independent of the PBMC source, EVs were mostly captured by monocytes and in a lower proportion by T lymphocytes. Capture of EV_PE was higher than of EV_NP in primary T lymphocytes, monocytes, and THP-1-derived macrophages. After inhibition by Wortmannin and Cytochalasin D, EV internalization by THP-1-derived macrophages was significantly inhibited but not completely abolished. No defined polarization profile of treated THP-1-derived macrophages could be identified. These findings provide evidence of EV modifications in PE, which enhance their uptake by monocytes and other immune cells, mainly through phagocytosis and endocytosis.</p>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"104417"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877067","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":"Exosome's role in ovarian disease pathogenesis and therapy; Focus on ovarian cancer and failure.","authors":"Hashem O Alsaab, Bandar Almutairy, Ali Othman Almobarki, Miad A Abu Mughaedh, Mohammad S Alzahrani","doi":"10.1016/j.jri.2024.104403","DOIUrl":"10.1016/j.jri.2024.104403","url":null,"abstract":"<p><p>In the eukaryotic system, exosomes are categorized as unique extracellular vesicles with dimensions ranging from 30 to 150 nm. These vesicles contain a variety of endogenous molecules, such as proteins, DNA, mRNA, microRNA, and circular RNA. They are essential for a wide range of metabolic events and have the potential to be used as therapeutic or diagnostic targets for a number of diseases, including ovarian diseases. By inducing changes in the surrounding environment, the donor exosomes transfer their contents to the receiving cells, so demonstrating the biological implications of major interactions between cells. Mesenchymal stem cells (MSCs) have produced exosomes have shown promise as a treatment for premature organ failure (POF or POI). Furthermore, exosomal transport has many complexities, and contributes to the pathophysiology of ovarian cancer by affecting cell growth, migration, metastastsis and etc. Owing to these facts, in this paper, we present the progress developed in the understanding of exosomes as a viable therapeutic avenue and indisputable prognostic targets in ovarian disorders.</p>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"104403"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813557","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":"Cross-reactivity of antigenic binding sites of antiphosphatidylserine/prothrombin antibodies in patients with pregnancy loss and epidermal growth factor.","authors":"Aiko Aoki, Toshitaka Sugi, Kei Kawana, Toshihiro Sugi, Rie Sakai","doi":"10.1016/j.jri.2024.104399","DOIUrl":"10.1016/j.jri.2024.104399","url":null,"abstract":"<p><strong>Background: </strong>Epidermal growth factor (EGF) protein family is essential for implantation and maintenance of normal pregnancy. Results of our previous study on the high incidence of autoantibodies to EGF in patients with pregnancy loss indicated a strong association between EGF autoantibodies and antiphosphatidylserine/prothrombin antibodies (aPS/PT), which are observed in the plasma of patients with thrombosis and adverse pregnancy outcomes.</p><p><strong>Objectives: </strong>To investigate the association between EGF autoantibodies and aPS/PT in patients with pregnancy loss.</p><p><strong>Patients and methods: </strong>Plasma specimens were analyzed from patients who experienced pregnancy loss. Direct binding studies using recombinant proteins of the fragments were conducted to determine the antigenic binding sites of aPS/PT, before examining the cross-reactivity of EGF and aPS/PT binding sites.</p><p><strong>Results: </strong>Of the 219 patients with pregnancy loss, 26 (11.9 %) were positive for aPS/PT. Moreover, incidence of antihuman EGF autoantibodies (anti-hEGF) was significantly higher in aPS/PT-positive patients than in aPS/PT-negative patients (18/26, 69.2 % and 58/193, 30.1 %, respectively; p = 0.0003). Of the aPS/PT-positive patients, 42.3 % recognized fragment 1 + 2 (F1 + 2), and 61.5 % recognized α-thrombin. Presence of anti-hEGF was correlated with recognition of α-thrombin but not of F1 + 2. Moreover, polyclonal antibodies against EGF recognized α-thrombin, and those against α- thrombin recognized hEGF.</p><p><strong>Conclusions: </strong>In patients with pregnancy loss, aPS/PT recognize F1 + 2 and α-thrombin. Furthermore, α-thrombin and hEGF are immunologically cross-reactive. Therefore, autoantibody-associated disruption of the EGF system may be a cause of pregnancy loss.</p>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"104399"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779976","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":"LncRNA-THBS4 affects granulosa cell proliferation and apoptosis in diminished ovarian reserve by regulating PI3K/AKT/mTOR signaling pathway.","authors":"Yiyue Fan, Dongmei Tian, Zili Lv, Shiyang Peng, Shaomi Zhu","doi":"10.1016/j.jri.2024.104419","DOIUrl":"10.1016/j.jri.2024.104419","url":null,"abstract":"<p><strong>Backgrounds: </strong>Recent studies have found Several lncRNAs were proved differential expression in diminished ovarian reserve (DOR) patients, however, the mechanism of DOR caused by lncRNAs is still largely unclear.</p><p><strong>Methods: </strong>High throughput sequencing was performed in ovarian GCs extracted from women with normal ovarian function and women with DOR. Bioinformation analysis was used to analyze the sequencing data and identify the differential expression of lncRNAs. Quantitative RT-PCR (qRT-PCR) was used to verify the sequencing results. Situ fluorescence hybridization (FISH) followed by confocal microscopy and qRT-PCR were used to explore the location and expression of LncRNA-THBS4 in GCs. The significantly enriched signaling pathways of LncRNA-THBS4 were identified by KEGG. The study used RNA interference technology to decipher LncRNA-THBS4 function by silencing LncRNA-THBS4 in GCs. Western blot and qRT-PCR were used to explore the mRNA and protein expressions of key factors of PI3Ks pathway. The pro-apoptotic protein and anti-apoptotic protein were detected by western blot. The proliferation and apoptosis of GCs were detected by MTT assay and Flow cytometry.</p><p><strong>Results: </strong>197 lncRNAs with significant differences in expression levels were detected between control and DOR group by high throughput sequencing. The study found the expression of LncRNA-THBS4 in GCs was positively correlated with Anti-Mullerian hormone (AMH) (p = 0.0020, r = 0.4742)、antral follicle count (AFC) (p = 0.0007, r = 0.5130)、good embryo rate (p = 0.0006, r = 0.5210), negatively correlated with basal FSH level (p = 0.0007, r = －0.5152). LncRNA-THBS4 was mainly localized in the cytoplasm of GCs. LncRNA-THBS4 silencing could inhibit the PI3Ks pathway; decrease the levels of anti-apoptotic protein, inhibit the proliferation of GCs; increase the levels of apoptosis protein, enhance the apoptosis of GCs.</p><p><strong>Conclusions: </strong>The expression level of lncRNA-THBS4 is correlated with ovarian function indicators and pregnancy outcomes in women. LncRNA-THBS4 may participate in the pathogenesis of DOR by affecting the proliferation and apoptosis of GCs via regulating PI3K/AKT/mTOR signaling pathway.</p>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"104419"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894913","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":"A high concentration of neutrophil extracellular traps is observed in humans and mice suffering from endometriosis.","authors":"Yuting Sun, Junhong Cai, Yanan Zhang, Shan Bao","doi":"10.1016/j.jri.2024.104414","DOIUrl":"10.1016/j.jri.2024.104414","url":null,"abstract":"<p><p>We wished to ascertain if there is an association between neutrophil extracellular traps and endometriosis (EMS). We collected the lesional tissues and normal endometrium of 30 patients suffering from endometriosis. Samples were also taken from healthy controls. Blood from the peripheral circulation was collected to isolate serum and neutrophils. A mouse model of endometriosis was also created. Expression of citrullinated histone and the myeloperoxidase level in tissue were measured by immunofluorescence staining and western blotting. The myeloperoxidase level in peripheral blood serum was measured by enzyme-linked immunosorbent assay. Staining (Trypan Blue) and flow cytometry were used to measure the apoptosis of neutrophils in peripheral blood. BALB/C mice were modeled by allotransplantation, and the experimental parameters noted above quantified. The myeloperoxidase content in the peripheral blood of patients with endometriosis was increased compared with that in healthy controls. Flow cytometry showed that the percent apoptosis of neutrophils in patients with endometriosis was lower than that in healthy controls. Expression of citrullinated histone was higher in the endometriosis group in humans and mice compared with respective controls according to immunofluorescence staining and western blotting. Our data suggest that a high concentration of neutrophil extracellular traps was observed in humans and mice suffering from endometriosis.</p>","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"104414"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807443","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":"Immunohistochemical examination of PNAd, α4β1 integrin and MUC-2 expressions in the secretary phase endometrium of women diagnosed with recurrent implantation failure.","authors":"Tiinçe Aksak, Ali Askin, Sait Polat, İbrahim Ferhat Ürünsak, Özdem Karaoğlan","doi":"10.1016/j.jri.2024.104420","DOIUrl":"10.1016/j.jri.2024.104420","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Successful embryo implantation is contingent upon the intricate interaction between the endometrium and the blastocyst. Recurrent implantation failure (RIF) signifies the clinical challenge of failing pregnancy post-transfer of high-quality embryos, fresh or frozen, in at least three in vitro fertilization (IVF) cycles, often in women under 40 years. Recent studies identify impaired blastocyst maternal tissue communication among recurrent implantation failure causes. Despite successful embryo transfer in vitro fertilization cycles, endometrial factors persist in women with recurrent implantation failure history, underscoring implantation's complexity. The implantation window, during which the endometrium becomes receptive to the blastocyst, involves the expression of key molecules that facilitate the implantation process. When the literature was examined, it was observed that comparative immunohistochemical studies on key molecules such as α4β1 integrin, MUC-2 and PNAd, which are thought to play a critical role in the endometrium before and during implantation, were limited. In this study, we aimed to investigate, through immunohistochemical and histological analyses, the roles of adhesion molecules in the secretory phase endometrium of patients diagnosed with RIF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Twenty-one patients diagnosed with recurrent implantation failure and 21 patients with a history of previous pregnancy at the Gynecology and Obstetrics Clinic of Balcalı Hospital, Faculty of Medicine, Çukurova University were clinically evaluated between days 19-21 of the menstrual cycle and included in the study. Endometrial biopsies, prepared for light and electron microscopy, received Hematoxylin and Eosin staining and anti-α4β1 integrin, anti-MUC-2, and anti-PNAd antibodies for immunohistochemistry. Blood samples were collected on the 2nd and 3rd days of the menstrual cycle to assess serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and thyroid-stimulating hormone (TSH).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;While FSH, LH, and E2 levels showed no significant difference, TSH was elevated in the recurrent implantation failure group. Structural differences in the endometrium included increased microvilli cells and reduced pinopod counts in infertile women compared to controls. In women with recurrent implantation failure MUC-2 expression were found to be elevated in the endometrial surface epithelium, while PNAd expression was reduced compared to the control group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;These findings suggest structural and molecular disparities during the endometrial receptivity window in recurrent implantation failure women may underlie infertility by hindering blastocyst adherence. Molecular studies are needed to elucidate the pathophysiology of the biomarkers whose presence in the endometrium we examined immunohistochemically and to discover new molecules.&lt;/p&gt;&lt;p&gt;&lt;strong","PeriodicalId":16963,"journal":{"name":"Journal of Reproductive Immunology","volume":"167 ","pages":"104420"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927277","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}