American Journal of Reproductive Immunology最新文献

{"title":"Body Fat Distribution and Glucose Homeostasis Is Affected by Perinatal Exposure to High Dietary Advanced Glycation End Products (AGEs) in Male Offspring","authors":"Zaher Merhi,&nbsp;Xiu Quan Du,&nbsp;Maureen J. Charron","doi":"10.1111/aji.70073","DOIUrl":"https://doi.org/10.1111/aji.70073","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>Exposures during the perinatal period, a phase of rapid development and growth, may have a profound and sustained effect on metabolic disturbances later in life. The pro-inflammatory advanced glycation end products (AGEs) are widely consumed in the Western diet. The purpose of this study was to determine whether perinatal exposure to these dietary AGEs alters metabolic parameters, in particular adiposity and glucose hemostasis, in male mice offspring.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Seven-week-old female CD1 mice were placed before mating and then throughout pregnancy and lactation on either a low AGE (L-AGE; <i>n</i> = 13) or high AGE (H-AGE; <i>n</i> = 13) diet. All offspring in both groups were weaned postnatal day 21 onto normal diet and studied through to 21 weeks of age. The offspring were counted and weighed weekly, starting at birth until 21 weeks of age, to assess the growth curve. At the time of sacrifice, Echo MRI was performed to measure adiposity and to record liver, white epididymal adipose tissue (WAT), and inguinal fat weights. Serum levels of leptin as well as insulin and glucose tolerance tests (ITT and GTT) were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The Body weight at birth of offspring of dams that were on H-AGE diet was significantly lower compared to the body weight of offspring of dams that were on L-AGE diet. Echo MRI data showed that the offspring of dams that were H-AGE diet had significantly lower fat mass, lower epididymal WAT fat weight, and lower inguinal fat weight but higher lean body mass and similar liver weight. They also had significantly higher glucose levels during GTT and ITT, as well as significantly lower serum leptin levels compared to the offspring of dams that were on the L-AGE diet.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results indicate that perinatal exposure to a maternal diet elevated in AGEs causes deficits in perinatal growth and impairment in glucose hemostasis in male mice. These findings suggest that AGEs may represent an important new class of mediators of adiposity and the metabolic syndrome.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786888","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":"Reproductive Outcomes of Women With Endometrial Fluid During IVF-ICSI Treatment: A Single-Center Experience","authors":"Burcu Tas Uzun,&nbsp;Emine Sen Bicak,&nbsp;Erinc Tekin,&nbsp;Hasan Ali Inal,&nbsp;Mete Caglar","doi":"10.1111/aji.70072","DOIUrl":"https://doi.org/10.1111/aji.70072","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To retrospectively evaluate whether endometrial fluid detected at transvaginal ultrasonography on the third day of the menstrual cycle in infertile patients undergoing in vitro fertilization/intracytoplasmic sperm injection–embryo transfer (IVF-ICSI/ET) affects pregnancy outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 148 patients who had undergone IVF-ICSI between 2010 and 2017 were included in this study. The participants were stratified according to the presence of endometrial fluid: Group 1 (control; <i>n</i> = 74) consisted of women without endometrial fluid and Group 2 (study; <i>n</i> = 74) of those with endometrial fluid. Baseline sociodemographic characteristics and reproductive outcomes were compared between the groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No difference was found between the groups in terms of age, body mass index, smoking rates, duration of infertility, etiology of infertility, baseline follicle-stimulating hormone, luteinizing hormone, estradiol, thyroid-stimulating hormone, and prolactin levels, duration of stimulation, stimulation protocol, antral follicle counts, total gonadotropin doses, peak E₂ and progesterone levels on the day of human chorionic gonadotropin (hCG) administration, or endometrial thickness at hCG administration and the day of transfer (<i>p</i> &gt; 0.05). The number of oocytes retrieved, metaphase II oocytes, two pronuclei, fertilization rates, and the rates of Grade I embryos per woman, as well as pronucleus counts, were comparable between the groups (<i>p</i> &gt; 0.05). However, the clinical pregnancy rate (CPR) (47.3% vs. 31.1%) and live birth rate (LBR) (41.9% vs. 24.3%) were both significantly lower in women with endometrial fluid compared to the control group (<i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This retrospective cohort study shows that the women with endometrial fluid in their IVF-ICSI/ET cycles exhibited lower CPR and LBR. Further prospective studies are needed to confirm the validity of our results.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770319","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":"Predictive Value of First-Trimester Aggregate Index of Systemic Inflammation (AISI) and Other Inflammatory Indices for Gestational Diabetes Mellitus and Associated Obstetric Outcomes","authors":"Esra Karatas,&nbsp;Atakan Tanacan,&nbsp;Osman Onur Ozkavak,&nbsp;Burcu Bozkurt Ozdal,&nbsp;Hatice Betul Ucar,&nbsp;Ozgur Kara,&nbsp;Dilek Sahin","doi":"10.1111/aji.70069","DOIUrl":"https://doi.org/10.1111/aji.70069","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>To investigate the value of the first-trimester aggregate index of systemic inflammation (AISI) and other combined inflammatory markers in the prediction of gestational diabetes mellitus (GDM) and related obstetric outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>The data of pregnant women diagnosed with GDM between September 2021 and November 2024, as well as an equal number of control patients, were retrospectively analyzed. The patients' AISI, neutrophil lymphocyte ratio (NLR), systemic immune-inflammatory index (SII), and systemic inflammatory response index (SIRI) values were calculated from the hemogram parameters of the participants at 11–14 weeks of gestation. The clinical characteristics, laboratory results, combined inflammatory indices, obstetric outcomes, the need for neonatal intensive care unit (NICU) admission, and the presence of composite adverse perinatal outcome (CAPO) of the groups were then compared. Receiver operating characteristic (ROC) curve analyses were performed to investigate the value of the indices that reached statistical significance in predicting GDM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The GDM group exhibited significantly higher SII and AISI values, rate of NICU admission, and CAPO compared to the control group (<i>p</i> = 0.036, <i>p</i> = 0.011, <i>p </i>&lt; 0.01, and <i>p </i>&lt; 0.01, respectively). The gestational age at birth was significantly lower in the GDM group compared to the control group, while the neonatal weight was higher (<i>p </i>&lt; 0.01, <i>p </i>&lt; 0.01, respectively). The ROC curve analyses yielded an area under the curve (AUC) of 0.566 and 0.581 for SII and AISI for GDM prediction, respectively (<i>p</i> = 0.036 and <i>p</i> = 0.011, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>First-trimester AISI and SII may be useful markers for identifying pregnancies at high risk for developing GDM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770416","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":"Associations of Serum Inflammatory Biomarkers During Pregnancy With Placental Pathology and Placental Gene Expression at Delivery","authors":"Linda M. Ernst,&nbsp;Alexa A. Freedman,&nbsp;Renee M. Odom-Konja,&nbsp;Lauren Keenan-Devlin,&nbsp;Gregory E. Miller,&nbsp;Steve Cole,&nbsp;Amy Crockett,&nbsp;Ann Borders","doi":"10.1111/aji.70062","DOIUrl":"https://doi.org/10.1111/aji.70062","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>We sought to investigate whether maternal inflammatory cytokines during pregnancy are associated with histologic inflammatory or vascular lesions in the placenta and/or correlated with gene expression patterns in the placenta.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method of Study</h3>\u0000 \u0000 <p>We leveraged data from a large randomized controlled trial (RCT) at a single site. Maternal serum was collected in the second and third trimesters, and a composite inflammatory score was created using five measured biomarkers (CRP, IL-6, IL-1ra, IL-10, and TNF-α). Placentas were collected at delivery for histological analysis and four major patterns of placental injury were characterized. Fresh small chorionic villous biopsies were collected for placental genome-wide mRNA profiling. Transcripts showing &gt;2-fold differential expression over the 4-SD range of circulating inflammatory biomarkers were reported, adjusting for potential confounders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The primary analysis included 601 participants. A one standard deviation increase in the third-trimester inflammatory composite was associated with increased odds of chronic inflammation in the placenta (OR: 1.23, 95% CI 1.01, 1.51;). This was driven primarily by elevations in IL-10 (OR: 1.37; 99% CI: 1.06, 1.77). Higher maternal IL-10 in circulation was associated with bioinformatic indications of reduced pro-inflammatory gene regulation pathways in the placenta (AP1 decreased 25%, <i>p</i> = 0.003; NF-kB decreased 53%, <i>p</i> = 0.003) and indications of increased STAT family signaling pathways which mediate signaling through the IL-10 receptor (increased 73%, <i>p</i> = 0.002).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results indicate that elevated maternal circulating IL-10 during pregnancy is associated with chronic inflammatory lesions in the placenta at delivery. Additionally, higher levels of circulating IL-10 are associated with upregulated STAT signaling pathways in placental tissues.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/aji.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762206","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":"Immunopathology of Endometriosis, Molecular Approaches","authors":"Sima Amidifar,&nbsp;Davood Jafari,&nbsp;Amir Hossein Mansourabadi,&nbsp;Sara Sadaghian,&nbsp;Abdolreza Esmaeilzadeh","doi":"10.1111/aji.70056","DOIUrl":"https://doi.org/10.1111/aji.70056","url":null,"abstract":"<div>\u0000 \u0000 <p>Endometriosis (EMS) is a common chronic gynecological disorder affecting 5%–10% of reproductive-age women, often causing infertility, dyspareunia, pain, and limitations in physical and sexual activities. This condition is defined by the presence of endometrial tissue outside the uterus, commonly explained by Sampson's theory of retrograde menstruation. Although its etiology remains unclear, genetic, epigenetic, hormonal imbalances, oxidative stress, and immune factors play critical roles. Immune dysregulation, involving inflammatory factors, cytokines, and immune cells facilitates the implantation, proliferation, angiogenesis, and development of ectopic endometrial stromal cells (ESCs). Research indicates that the implantation of ESCs in the peritoneum triggers an inflammatory response, recruiting various immune cells and leading to a cycle of inflammation characterized by elevated growth factors and cytokines. In this review, we discuss the immune system's role in EMS pathogenesis, emphasizing the contributions of immune cells, inflammatory mediators, oxidative stress, and so forth. This review also highlights that while current treatments, including hormonal therapies and surgical interventions, aim to alleviate symptoms and improve fertility, emerging evidence suggests that advancements in immunotherapies targeting specific immune cell activities hold promise as innovative future treatment strategies enhancing healthcare management for affected women.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698712","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 Decrease of Antibodies Against SARS-CoV-2 Antigens Does Not Reflect a Decrease of Neutralization Rate: Comment","authors":"Hinpetch Daungsupawong,&nbsp;Viroj Wiwanitkit","doi":"10.1111/aji.70068","DOIUrl":"https://doi.org/10.1111/aji.70068","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698713","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":"Targeted Degradation Technology Based on the Autophagy-Lysosomal Pathway: A Promising Strategy for Treating Preeclampsia","authors":"Lin Xiao,&nbsp;Zilin Mei,&nbsp;Jin Chen,&nbsp;Kai Zhao,&nbsp;Huiping Zhang,&nbsp;Surendra Sharma,&nbsp;Aihua Liao,&nbsp;Chunyan Liu","doi":"10.1111/aji.70066","DOIUrl":"https://doi.org/10.1111/aji.70066","url":null,"abstract":"<div>\u0000 \u0000 <p>In recent years, targeted protein degradation (TPD) strategies leveraging the autophagy-lysosomal pathway (ALP) have transcended the limitations of conventional drug molecules, emerging as a highly promising approach for selectively eliminating disease-related proteins via the cell's intrinsic degradation machinery. These TPD methods, such as autophagosome-tethering compounds (ATTEC), autophagy-targeting chimera (AUTAC), AUTOphagy-TArgeting chimera (AUTOTAC), and chaperone-mediated autophagy (CMA) targeting chimera, exhibit efficacy in degrading misfolded protein aggregates associated with neurodegenerative disorders. Moreover, the excessive accumulation of misfolded proteins or protein complexes in the placenta has been identified as a significant contributor to preeclampsia (PE). Given the lack of effective treatments for PE, the application of autophagy-mediated TPD technology presents a novel therapeutic avenue. This review draws parallels between misfolded protein aggregates in neurodegenerative diseases and placenta-derived PE, integrating a substantial number of full-text studies. By harnessing TPD technologies grounded in the ALP, these autophagic degraders offer a pioneering approach for targeted therapy in PE by dismantling potential targets. Presently, there is limited exploration of ALP technology for identifying target proteins in the placenta. Nonetheless, we have proposed several potential target proteins, laying the groundwork for future therapeutic endeavors.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554831","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":"Causal Relationship Between Abortion and Endometriosis: A Bidirectional Two-Sample Mendelian Randomization Study","authors":"Yan Huang,&nbsp;Deyu Zhang,&nbsp;Yingfang Zhou,&nbsp;Chao Peng","doi":"10.1111/aji.70064","DOIUrl":"https://doi.org/10.1111/aji.70064","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Problem</h3>\u0000 \u0000 <p>The relationship between abortion and endometriosis (EMS) has been inconsistent in previous observational studies and remains controversial. We intended to examine the causal relationship between abortion and EMS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods of Study</h3>\u0000 \u0000 <p>We conducted a Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary statistics, drawing data from the FinnGen database and the UK Biobank. The primary analysis utilized the random-effects inverse variance weighted (IVW) approach, complemented by weighted median, weighted mode, and MR–Egger methods. Comprehensive sensitivity analyses were conducted, encompassing the Cochran's <i>Q</i> statistic for assessing heterogeneity and MR-PRESSO to detect pleiotropy. Additionally, Leave-One-Out (LOO) analysis was conducted to confirm the stability of our results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The IVW method revealed no statistically significant causal association between various types of abortion and EMS. Specifically, the odds ratios (ORs) were as follows: medical abortion (OR 0.96, 95% CI: 0.78–1.18, <i>p</i> = 0.72), spontaneous abortion (OR 0.99, 95% CI: 0.81–1.21, <i>p</i> = 0.92), and other types of abortions (OR 1.01, 95% CI: 0.99–1.03, <i>p</i> = 0.36), indicating no significant effects on the risk of EMS. Similarly, analysis in the reverse direction showed no significant causal effects of EMS on the likelihood of experiencing any type of abortion, with ORs for medical abortion (0.97, 95% CI: 0.91–1.03, <i>p</i> = 0.33), spontaneous abortion (0.98, 95% CI: 0.92–1.04, <i>p</i> = 0.50), and other abortions (1.30, 95% CI: 0.76–2.23, <i>p</i> = 0.34). Sensitivity analyses supported these findings, demonstrating no evidence of horizontal pleiotropy or significant heterogeneity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our MR results do not support a causal relationship between abortion and EMS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530373","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 Mast Cells in the Development and Advancement of Endometriosis","authors":"Masoud Hassanzadeh Makoui,&nbsp;Shiva Fekri,&nbsp;Reza Hassanzadeh Makoui,&nbsp;Negar Ansari,&nbsp;Abdolreza Esmaeilzadeh","doi":"10.1111/aji.70019","DOIUrl":"https://doi.org/10.1111/aji.70019","url":null,"abstract":"<div>\u0000 \u0000 <p>Endometriosis is a medical condition identified by the presence of endometrium-like tissue outside the uterus. This condition is known to result in symptoms such as frequent pelvic pain, infertility, and irregularities in the menstrual cycle. The development of endometriosis is complex and, involving abnormal body responses, hormonal imbalances, and genetic predispositions. Although endometriosis is common and affects quality of life, its mechanisms of development and progression are not fully understood. Mast cells (MCs), a type of immune cell, are renowned for their involvement in allergic and inflammatory responses. These cells are essential in the modulation of the immune system and the inflammatory process through the secretion of different mediators like histamine, cytokines, and proteases. In recent years, MCs have been shown to play a role in the pathogenesis of many diseases, including endometriosis. This article explores the relationship between MCs and endometriosis, including disease development, pain perception, angiogenesis, and other important processes. It elucidates how MCs, via their mediators, actively participate in the pathogenesis of endometriosis and the associated inflammatory environment. Moreover, the research emphasizes the potential of targeting MCs as a therapeutic approach for treating endometriosis. Insight into the interplay between endometriosis and MCs holds promise for developing innovative therapeutic strategies to manage this condition effectively.</p>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530315","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":"Finding Potential Drug Targets for Pre-Eclampsia Using Mendelian Randomisation and Colocalisation Analysis","authors":"Yuexin Xu,&nbsp;Yingzi Pan,&nbsp;Chengqian Wu,&nbsp;Tingting Zhao,&nbsp;Jiayan Miao,&nbsp;Xiaohong Ji","doi":"10.1111/aji.70063","DOIUrl":"https://doi.org/10.1111/aji.70063","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Pre-eclampsia (PE) is a common complication of pregnancy and there is an urgent need for new drug targets. We performed whole proteome-wide Mendelian randomisation (MR) and colocalisation analyses to identify potential therapeutic targets for PE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Methods</h3>\u0000 \u0000 <p>A two-sample MR study was conducted using summary-level statistics of 734 plasma proteins retrieved from large genome-proteome-wide association studies. The summary statistics of PE or eclampsia were obtained from the FinnGen consortium. Wald ratio and Inverse variance weighted (IVW) were used to assess the causal association between proteins and PE. Colocalisation analyses were conducted to examine whether the identified proteins and PE shared incidental variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Genetically predicted circulating levels of 42 proteins were associated with PE risk after Benjamini-Hochberg correction. Nineteen of the gene-predicted proteins showed evidence of increased PE risk (CRELD1, CPA4, AHSG, NFASC, QDPR, NTM, PZP, FAM171B, RTN4R, FLRT2, ADH4, ADM, SPINK5, LGALS4, CKM, SPON2, UROS, CXCL10 and APOBEC3G); 23 proteins reduced the risk of PE (CLIC5, NEO1, SWAP70, KLK8, VWA2, FSTL1, CXCL11, APOB, NPPB, CNTN4, IL12B, ACHE, TCN1, GFRA2, GNMT, HPGDS, DPT, MANBA, SPARCL1, ACE, FUT8, BST1 and ACP1). Bayesian colocalisation indicated that six proteins (VWA2, ACHE, CXCL10, PZP, AHSG and UROS) and PE, which were identified as high evidence of colocalisation with PE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study provides evidence of the causal association between genetically predicted 42 proteins associated with PE risk, which might be promising drug targets for PE.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"93 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530314","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}