F&S science最新文献

{"title":"Enhanced ovarian FKBP51 expression is associated with ovarian aging: a molecular insight for age-related fertility in women","authors":"Papri Sarkar M.D. , Monica Moore M.Sc , Asli Ozmen PhD , Busra Cetinkaya-Un Ph.D , Vitko Julie M.D. , Anthony N. Imudia M.D , Charles J. Lockwood M.D. , Umit A. Kayisli Ph.D. , Ozlem Guzeloglu-Kayisli Ph.D.","doi":"10.1016/j.xfss.2025.01.004","DOIUrl":"10.1016/j.xfss.2025.01.004","url":null,"abstract":"<div><h3>Objective</h3><div>To study the relationship between FK506-binding protein 51 (FKBP51) and ovarian aging and/or diminished ovarian reserve (DOR) in human ovaries by comparing FKBP51 levels in granulosa cells (GCs) and cumulus cells (CCs), collected during controlled ovarian stimulation (COS) from women of advanced reproductive age and/or with a diagnosis of DOR with that of young women with normal ovarian reserve. To explore the association between increased FKBP51 expression and human ovarian aging further, expression of FKBP51 was compared in ovarian stroma of postmenopausal vs. premenopausal women. Lastly, this relation was further queried by comparing ovarian expression of several collagen genes as markers of ovarian fibrosis in 14-month-old wild-type (<em>Fkbp5</em><sup><em>+/+</em></sup>) and <em>Fkbp5</em> knockout (<em>Fkbp5</em><sup><em>−/−</em></sup>) mice.</div></div><div><h3>Design</h3><div>Laboratory-based experimental study.</div></div><div><h3>Subjects</h3><div>Samples collected included follicular fluid, CCs, GCs, and serum from group 1: young women with normal ovarian reserve (<35 years; n = 12); group 2: DOR (antimüllerian hormone <1 ng/mL; n = 10); and group 3: women of advanced age with normal ovarian reserve (>37 years; n = 8). Ovarian stromal tissues obtained from surgical specimen of post-menopausal (50–65 years; n = 6) and pre-menopausal (18–30 years; n = 6). Ovarian tissues from 14-month-old <em>Fkbp5</em><sup><em>+/+</em></sup> <em>and Fkbp5</em><sup><em>−/−</em></sup> mice. All the experiments were performed at an academic-affiliated assisted reproductive technology unit/laboratory.</div></div><div><h3>Exposure</h3><div>Comparison of FKBP51 expression in GCs and CCs from women undergoing COS, ovarian stromal tissue from pre- and post-menopausal women, and ovarian tissue from aged <em>Fkbp5</em><sup><em>+/+</em></sup> <em>and Fkbp5</em><sup><em>−/−</em></sup> mice.</div></div><div><h3>Main Outcome Measures</h3><div>(1) Level of FKBP51 in human GCs and CCs, collected during COS by performing real-time quantitative polymerase chain reaction (qPCR). (2) Immunohistochemistry to detect FKBP51 levels and Picrosirius Red staining to detect collagen deposition in human ovarian stromal tissue. (3) Real-time qPCR to compare expression levels of several collagen genes in <em>Fkbp5</em><sup><em>+/+</em></sup> and <em>Fkbp5</em><sup><em>−/−</em></sup> old mice ovaries. Serum and follicular fluid levels of transforming growth factor β1, and soluble endoglin measured by enzyme-linked immunosorbent assay.</div></div><div><h3>Results</h3><div>Immunohistochemistry revealed that FKBP51 histologic score levels in ovarian stromal tissue were significantly higher in postmenopausal vs. premenopausal women (mean ± SEM, 160.52 ± 17.75 vs. 120.67 ± 14.33; <em>P</em>=.002). Stronger Picrosirius Red staining, suggestive of fibrosis, was seen in ovarian stromal tissue of postmenopausal vs. premenopausal women (54.06 ± 6.94 vs. 37.5","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 152-163"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prioritization of potential drug targets in ovarian-related diseases: Mendelian randomization and colocalization analyses","authors":"Yanggang Hong M.D.","doi":"10.1016/j.xfss.2025.02.003","DOIUrl":"10.1016/j.xfss.2025.02.003","url":null,"abstract":"<div><h3>Objective</h3><div>To identify key genes and potential drug targets for ovarian-related diseases through genome-wide Mendelian randomization (MR) and colocalization analyses.</div></div><div><h3>Design</h3><div>We conducted a comprehensive two-sample MR analysis to estimate the causal effects of blood expression quantitative trait loci (eQTLs) on ovarian-related diseases, followed by colocalization analyses to verify the robustness of the expression instrumental variables (IVs). Phenome-wide association studies (PheWAS) were also performed to evaluate the horizontal pleiotropy of potential drug targets and possible side effects.</div></div><div><h3>Subjects</h3><div>Large cohorts of European ancestry.</div></div><div><h3>Exposure</h3><div>The exposure in this study was the genetic variants (eQTLs) associated with gene expression levels, considered a form of lifelong exposure. Expression quantitative trait loci data were obtained from the eQTLGen Consortium, encompassing 16,987 genes and 31,684 cis-eQTLs derived from blood samples of healthy individuals of European ancestry.</div></div><div><h3>Main Outcome Measures</h3><div>The primary outcome measures were the identification of genes causally associated with ovarian-related diseases and the validation of these genes as potential therapeutic targets.</div></div><div><h3>Results</h3><div>Our study revealed that specific genes such as CD163L1, PPP3CA, MTAP, F12, NRM, BANK1, ZNF66, GNA15, and SLC6A9 were associated with ovarian endometriosis, ovarian cysts, and polycystic ovarian syndrome. Through MR and colocalization analyses, we identified potential drug targets, including CTNNB1, PTPN7, and ABCB4, with strong evidence of colocalization with ovarian-related diseases. Sensitivity analyses confirmed the robustness of our findings, showing no evidence of horizontal pleiotropy or heterogeneity.</div></div><div><h3>Conclusion</h3><div>This research highlights the significance of precision medicine approaches in identifying genetic factors underlying ovarian-related diseases and provides a foundation for developing targeted therapies, enhancing diagnostic accuracy, and improving treatment strategies for ovarian-related diseases.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 164-176"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic insights into the immunological basis of male infertility: a translational perspective","authors":"Yi Wang M.D. ,&nbsp;Yanggang Hong M.D.","doi":"10.1016/j.xfss.2025.02.002","DOIUrl":"10.1016/j.xfss.2025.02.002","url":null,"abstract":"<div><h3>Objective</h3><div>To elaborate the causal relationships between specific immunocyte phenotypes and male infertility.</div></div><div><h3>Design</h3><div>Mendelian randomization using genome-wide association study data.</div></div><div><h3>Subjects</h3><div>Large cohorts of European ancestry.</div></div><div><h3>Exposure</h3><div>731 immunocyte phenotypes or male infertility.</div></div><div><h3>Main Outcomes Measures</h3><div>Genetic variants were used as instrumental variables to infer causality, minimizing confounding and bias. The causal associations were assessed using the inverse variance-weighted (IVW) method for primary analysis, and the findings were validated using MR-Egger, Weighted Median, Simple Mode, and Weighted Mode approaches. Additional sensitivity analyses were performed to validate the robustness of the findings.</div></div><div><h3>Results</h3><div>Our analysis identified significant causal associations between specific immunocyte phenotypes and male infertility. Phenotypes such as naive-mature B cell %lymphocyte (odds ratio [OR] = 1.257) and IgD− CD38dim %B cell (OR = 1.100) were positively associated with increased infertility risk, whereas phenotypes like CD39+ CD8br %T cell (OR = 0.856) and B cells activator of the TNF-α family receptor (BAFF-R) on transitional (OR = 0.833) were negatively associated, suggesting a protective effect. Additionally, reverse MR analysis revealed that male infertility might causally affect certain immunocyte phenotypes, including CD14- CD16+ monocyte %monocyte (OR = 1.049).</div></div><div><h3>Conclusion</h3><div>This study provides robust evidence for the causal role of specific immunocyte phenotypes in male infertility and highlights the bidirectional relationship between immune function and reproductive health. These findings provide new insights into the immunological factors contributing to male infertility and suggest potential biomarkers and therapeutic targets for future research and clinical interventions.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 130-140"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “From the Editor-in-Chief” (F S Sci 2025;6:1–3)","authors":"","doi":"10.1016/j.xfss.2025.02.005","DOIUrl":"10.1016/j.xfss.2025.02.005","url":null,"abstract":"","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Page 261"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct assessment of hereditary hemochromatosis in preimplantation genetic testing","authors":"Qinnan Zhang Ph.D.,&nbsp;Maria Katz M.Sc.,&nbsp;Benjamin Podgursky M.Sc.,&nbsp;Nicholas Schuch B.S.,&nbsp;Shenglai Li M.Sc.,&nbsp;Noor Siddiqui M.Sc.,&nbsp;Funda Suer Ph.D.,&nbsp;Yuntao Xia Ph.D.","doi":"10.1016/j.xfss.2024.12.003","DOIUrl":"10.1016/j.xfss.2024.12.003","url":null,"abstract":"<div><h3>Objective</h3><div>Hereditary hemochromatosis (HH) is a common genetic disorder characterized by iron overload, which, if undiagnosed, can lead to severe organ damage. There are 4 types of HH. Type 1 HH, the most common form, is primarily caused by a common variant in Western Europe (p.Cys282Tyr, C282Y, or c.845 G&gt;A). It is generally preventable during in vitro fertilization if proper genetic testing is performed before implantation. Here, we demonstrated a direct detection and cost-effective approach using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in preimplantation genetic testing (PGT) settings.</div></div><div><h3>Design</h3><div>We began by validating the assay with genomic deoxyribonucleic acid (DNA) from Coriell cell lines of known HFE C282Y genotypes, followed by testing patients’ genomic DNA samples. After establishing the assay on genomic DNA, we extended the assay to whole-genome amplified DNA from embryo biopsies.</div></div><div><h3>Subjects</h3><div>The subjects include cell line samples and human specimens and human embryo biopsies.</div></div><div><h3>Exposure</h3><div>Patients and embryos either carried or did not carry the HFE C282Y variant in their genome. No intervention was applied.</div></div><div><h3>Main Outcome Measures</h3><div>The readout included the genotype of samples at the HFE C282Y locus and accuracy of PCR-RFLP results.</div></div><div><h3>Results</h3><div>An accuracy of &gt;99% was achieved across 80 cell line samples, 38 patient samples, and 81 embryo biopsies.</div></div><div><h3>Conclusion</h3><div>In this study, we demonstrated the feasibility of using the PCR-RFLP approach to PGT. Specifically, we validated the assay for the HFE C282Y variant, the primary cause of type 1 hemochromatosis. The assay was tested on genomic DNA and DNA resulting from whole-genome amplification, achieving &gt;99% accuracy, sensitivity, precision, and specificity. These results also suggest the possibility for extending the PCR-RFLP approach to cover a broader range of conditions, such as spinal muscular atrophy, to benefit more patients currently ineligible for testing at PGT laboratories.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 195-201"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stearoyl–coenzyme A desaturase enhances cell survival in human uterine leiomyoma","authors":"Allison S. Komorowski M.D.,&nbsp;John S. Coon V M.S.,&nbsp;Melania Anton B.S.,&nbsp;Azna Zuberi Ph.D.,&nbsp;Olivia Sotos B.S.,&nbsp;Serdar E. Bulun M.D.,&nbsp;Ping Yin M.D., Ph.D.","doi":"10.1016/j.xfss.2025.01.005","DOIUrl":"10.1016/j.xfss.2025.01.005","url":null,"abstract":"<div><h3>Objective</h3><div>Stearoyl-CoA desaturase (SCD1) is an enzyme that catalyzes the conversion of saturated delta-9 fatty acids to monounsaturated fatty acids. SCD1 is highly expressed in various cancers and facilitates cancer cell survival, tumor growth, and metastasis. This study aimed to assess SCD1 expression and function in uterine leiomyoma and matched myometrial tissue and evaluate the impact of SCD1 inhibition on leiomyoma cell viability and apoptosis.</div></div><div><h3>Design</h3><div>Gene set enrichment analysis was performed to determine whether lipid metabolism pathways are dysregulated in leiomyoma. To assess the function of SCD1, primary leiomyoma and myometrial cells, as well as a CRISPR-engineered leiomyoma-relevant <em>MED12</em> mutant human uterine smooth muscle (UtSM) cell line, were treated with <em>SCD1</em> small interfering RNA or a small molecule inhibitor of SCD1, CAY10566. Cell viability and apoptosis assays, real-time quantitative polymerase chain reaction, and immunoblot analyses were performed to evaluate cell function in response to treatment.</div></div><div><h3>Subjects</h3><div>Leiomyoma and myometrial tissues were obtained from premenopausal individuals designated female at birth (n = 30) undergoing myomectomy or hysterectomy.</div></div><div><h3>Exposure</h3><div>SCD1 inhibition by small interfering RNA and CAY10566 treatment.</div></div><div><h3>Main Outcome Measures</h3><div>Messenger RNA (mRNA) and protein levels and cell viability and apoptosis.</div></div><div><h3>Results</h3><div>Gene set enrichment analysis revealed that the cholesterol homeostasis pathway was significantly different in leiomyoma vs. adjacent myometrial tissues. Among the genes in this pathway, SCD1 mRNA levels were found to be significantly higher in leiomyoma than in matched myometrium. SCD1 inhibition by small interfering RNA or CAY10566 decreased antiapoptotic BCL2 mRNA and protein levels and cell viability in primary leiomyoma but not myometrial cells. SCD1 protein levels were significantly higher in the mutant MED12 UtSM cell line than in the wild-type MED12 UtSM cell line. CAY10566 treatment specifically decreased cell viability and increased apoptosis in mutant MED12 UtSM cells, with increased protein levels of cleaved caspase 3, cleaved PARP, and DDIT3 in mutant MED12 UtSM but not in wild-type MED12 UtSM cells.</div></div><div><h3>Conclusion</h3><div>SCD1, an enzyme involved in lipid homeostasis, may play an important role in promoting leiomyoma growth and represents a novel target for the treatment of leiomyoma.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 202-212"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From the Editor-in-Chief","authors":"William H. Catherino MD, PhD","doi":"10.1016/j.xfss.2025.01.001","DOIUrl":"10.1016/j.xfss.2025.01.001","url":null,"abstract":"","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Pages 1-3"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial activator BGP-15 protects sperm quality against oxidative damage and improves embryo developmental competence","authors":"Macarena B. Gonzalez Ph.D. ,&nbsp;Nicole O. McPherson Ph.D. ,&nbsp;Haley S. Connaughton B.Sc. ,&nbsp;Yasmyn E. Winstanley Ph.D. ,&nbsp;David T. Kennedy Ph.D. ,&nbsp;Carl A. Campugan Ph.D. ,&nbsp;Mark A. Febbraio Ph.D. ,&nbsp;Michael Barry M.C.E. ,&nbsp;Ryan D. Rose Ph.D. ,&nbsp;Rebecca L. Robker Ph.D.","doi":"10.1016/j.xfss.2024.12.001","DOIUrl":"10.1016/j.xfss.2024.12.001","url":null,"abstract":"<div><h3>Objective</h3><div>To study the efficacy of mitochondrial activator BGP-15 to preserve sperm quality and competence against cellular damage.</div></div><div><h3>Design</h3><div>Spermatozoa from mice or humans were treated in vitro with BGP-15, and sperm quality markers were assessed. Spermatozoa from young (8–12 weeks old) or reproductively old (&gt;14 months old) mice were treated with BGP-15 for 1 hour and assessed for sperm quality and preimplantation embryo development after in vitro fertilization. The safety of BGP-15 on offspring outcomes was assessed through embryo transfers. In parallel studies, spermatozoa from healthy (not infertile) men were incubated in hydrogen peroxide, to induce oxidative stress, plus increasing doses of BGP-15, and sperm quality was evaluated. Spermatozoa from patients undergoing assisted reproductive technology (ART) treatment were incubated in the optimized dose of BGP-15 for 30 minutes, and sperm quality was assessed.</div></div><div><h3>Subjects</h3><div>C57BL/6 mice (N = 4–15 per group) for sperm quality and embryo development. CBAF1 mice (n = 6 per group) produced embryos for transfer. Human spermatozoa were from men with no infertility diagnosis (n = 14-20) or men undergoing ART (n = 33) at a local fertility clinic.</div></div><div><h3>Exposure</h3><div>Mouse spermatozoa were treated with 10-μM BGP-15. Human spermatozoa were treated with BGP-15 at doses from 1 to 100 μM.</div></div><div><h3>Main Outcome Measures</h3><div>Sperm quality measures (mouse and human) included motility, mitochondrial membrane potential (JC-1 dye), deoxyribonucleic acid (DNA) fragmentation (“HALO” assay), and DNA oxidation (8-oxoguanine immunodetection). Mouse embryo and offspring measures included on-time development after in vitro fertilization, morphokinetic analysis, and blastocyst inner cell mass and trophectoderm cell number, and growth and development from birth to 21 days postnatally.</div></div><div><h3>Results</h3><div>BGP-15 increased sperm motility and mitochondrial membrane potential and decreased DNA oxidation in old mice. BGP-15 improved on-time development of 2-cell and blastocyst embryos and increased the inner cell mass blastomere number. Embryos from BGP-15-treated mouse spermatozoa produced normal offspring. In human spermatozoa subjected to in vitro oxidative stress, BGP-15 increased motility by 45% and prevented DNA fragmentation (by 45%) and oxidative damage (by 60%). In spermatozoa from men attending a fertility clinic, BGP-15 increased motility by 12% and reduced both DNA oxidation and fragmentation by &gt;20%.</div></div><div><h3>Conclusion</h3><div>BGP-15 protects sperm against cellular damage and has the potential to improve ART outcomes.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Pages 42-54"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uterine pathology and microbiome among patients with endometrial polyps and fibroids","authors":"Sabrine Bensouda M.D. ,&nbsp;Sarah C. Cromack M.D. ,&nbsp;Allison S. Komorowski M.D. ,&nbsp;Elena HogenEsch M.D. ,&nbsp;Matthew J. Schipma Ph.D. ,&nbsp;Xinkun Wang Ph.D. ,&nbsp;Hailie Fowler M.S. ,&nbsp;MaryEllen Pavone M.D., M.S.C.I. ,&nbsp;Stefan J. Green Ph.D. ,&nbsp;Lia A. Bernardi M.D., M.S.C.I. ,&nbsp;Jennifer B. Bakkensen M.D., M.S.","doi":"10.1016/j.xfss.2024.12.002","DOIUrl":"10.1016/j.xfss.2024.12.002","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the uterine microbiome among women with endometrial polyps and submucosal fibroids and to compare results between endometrial sampling techniques.</div></div><div><h3>Design</h3><div>Patients with polyps or fibroids were prospectively recruited before hysteroscopy, whereas patients undergoing retrieval for planned oocyte cryopreservation were recruited prospectively as controls. Three specimen types obtained for each patient were the distal 5 mm of an embryo catheter passed to the uterine fundus (C), endometrial tissue from an endometrial biopsy (T), and formalin-fixed paraffin-embedded (FFPE) endometrial tissue from the same endometrial biopsy. 16S ribosomal RNA gene amplicon sequencing was performed to analyze the structure of the endometrial microbiome.</div></div><div><h3>Subjects</h3><div>Thirty-seven participants including 28 women with polyps and/or fibroids and 9 controls.</div></div><div><h3>Exposure</h3><div>None.</div></div><div><h3>Main Outcome Measures</h3><div>Microbial taxonomic alpha and beta diversity; differential abundance of taxa.</div></div><div><h3>Results</h3><div>Across all sample types, participants with polyps had higher microbial alpha diversity than controls (4.3 vs. 5.1, <em>q</em> = 0.049), and microbial communities were significantly different (pairwise Permutational Multivariate Analysis of Variance (PERMANOVA) pseudo-F = 2.1, <em>q</em> = 0.003). These differences were observed when examining C specimens alone (5.4 vs. 6.4, <em>q</em> = 0.001; pairwise PERMANOVA pseudo-F = 2.5, <em>q</em> = 0.003), although they did not reach significance when examining either T or FFPE specimens alone. Participants with fibroids had similar alpha diversity yet significant differences in beta diversity compared with controls in analyses combining all specimens (pairwise PERMANOVA pseudo-F = 1.475, <em>q</em> = 0.030); however, these differences did not achieve significance when analyzing C, T, or FFPE specimens alone. When comparing C and T specimens vs. FFPE specimens overall, alpha diversity was significantly higher (<em>q</em> &lt; 0.001 and <em>q</em> &lt; 0.001, respectively) and there were significant differences in beta diversity (<em>q</em> &lt; 0.003 and <em>q</em> &lt; 0.003, respectively). Analyses of C specimens generated a larger number of significantly differentially abundant taxa compared with other sampling methods. Although not statistically significant, relative abundance of putative pathogens was higher in participants with polyps than controls regardless of sampling technique.</div></div><div><h3>Conclusions</h3><div>Results of this exploratory study suggest that significant microbial differences exist among patients with endometrial polyps vs. healthy controls. However, results varied by sampling technique, highlighting a need to identify optimal sampling methods before validating findings in larger prospective cohort studies.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Pages 107-116"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2X4 receptor mediates macrophage infiltration leading to endometriotic cyst epithelium proliferation and hyperalgesia in mouse model","authors":"Hiroki Nagata M.D. ,&nbsp;Takeshi Y. Hiyama Ph.D. ,&nbsp;Misaki Inoue B.Sc. ,&nbsp;Shanshan Xu M.Sc. ,&nbsp;Ikumi Wada M.D. ,&nbsp;Yuki Yoshimura Ph.D. ,&nbsp;Kazuomi Nakamura Ph.D. ,&nbsp;Yukihiro Azuma M.D. Ph.D. ,&nbsp;Tasuku Harada M.D., Ph.D. ,&nbsp;Fuminori Taniguchi M.D., Ph.D.","doi":"10.1016/j.xfss.2024.10.007","DOIUrl":"10.1016/j.xfss.2024.10.007","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the effects of a P2X4 receptor (P2X4R)-specific antagonist on murine endometriotic-like lesions and human endometriotic stromal cells.</div></div><div><h3>Design</h3><div>Experimental study using an in vivo mouse endometriosis model and in vitro primary culture of human endometriotic stromal cells. NC-2600, an antagonist of the P2X4 ionotropic ATP receptor (P2X4R), was orally administered to the mice and cells. Gene expression analyses for cytokines were conducted in the endometriotic-like cysts and vaginal portion of mice, and immunohistochemistry was performed to evaluate the proliferative activity and localization of macrophages in addition to cytokine expression. The sensation of murine vaginal pain was evaluated using visceromotor responses.</div></div><div><h3>Results</h3><div>NC-2600 reduced the proliferation of the cyst epithelium and vaginal pain sensation. In both cysts and vaginas, P2X4R is mainly expressed in macrophages, and NC-2600 reduces the number of tissue macrophages and reverses the elevated expression of InterleukinL-33 and cyclooxygenase-2 in animals with endometriosis.</div></div><div><h3>Conclusion</h3><div>These results indicate unknown pathophysiological roles of P2X4R expressed in local macrophages at the injury site of endometriosis and in the vagina, suggesting the potential therapeutic effects of orally administered P2X4R inhibitors for alleviating the symptoms of endometriosis.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Pages 73-84"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}