F&S science最新文献

{"title":"The dual nature of micronutrients on fertility: too much of a good thing?","authors":"Aron Moazamian, Elisa Hug, Pauline Villeneuve, Stéphanie Bravard, Richard Geurtsen, Jorge Hallak, Fabrice Saez, Robert John Aitken, Parviz Gharagozloo, Joël R Drevet","doi":"10.1016/j.xfss.2025.02.004","DOIUrl":"10.1016/j.xfss.2025.02.004","url":null,"abstract":"<p><strong>Objective: </strong>To study the effects of generally considered safe doses of antioxidant micronutrient supplementation on semen parameters, systemic redox balance, sperm DNA structural integrity, and fertility.</p><p><strong>Design: </strong>Given ethical limitations in human studies, this dose escalation study examined the effects of common water-soluble antioxidant micronutrients (vitamin C, zinc, folate, and carnitine) on semen parameters, redox status, DNA integrity, and fertility outcomes in healthy male mice over one spermatogenic cycle. The study was partially repeated at the highest carnitine dose for pregnancy outcomes and comparatively assessed in subfertile, oxidatively stressed mice.</p><p><strong>Subjects: </strong>\"Fertile/healthy\" (CD1) and \"Subfertile/oxidatively stressed\" (gpx5^-/-) mice.</p><p><strong>Exposure: </strong>Water-soluble micronutrients (vitamin C, zinc, folate, and carnitine).</p><p><strong>Intervention: </strong>N/A MAIN OUTCOME MEASURES: Sperm parameters included count, motility, viability, and acrosome integrity. Systemic redox status was evaluated in blood, measuring malondialdehyde, thiol levels, and total antioxidant capacity. Sperm DNA parameters were examined for oxidation (8-OHdG staining), fragmentation (TUNEL), and decondensation (toluidine blue). Pregnancy outcomes were also assessed in CD1 mice fed carnitine.</p><p><strong>Results: </strong>In healthy mice, increasing doses of individual micronutrients had minimal effects on semen parameters. However, high doses of all four micronutrients significantly disrupted the redox balance in blood plasma and compromised sperm DNA integrity in an ingredient-specific manner. Moderate to high doses of carnitine caused severe DNA fragmentation, a finding confirmed in a subsequent experiment using the highest carnitine dose. In this follow-up experiment, male mice supplemented with carnitine and mated with females showed decreased pregnancy rates and fewer total pups born. Conversely, in oxidatively stressed mice, high-dose carnitine had the opposite, beneficial effect of improving sperm DNA integrity.</p><p><strong>Conclusions: </strong>At high doses, antioxidants can induce reductive stress, damaging vital molecular components of sperm cells such as DNA. Although strong evidence supports the use of preconception antioxidants to boost semen quality, healthcare professionals should assess oxidative stress levels when possible and recommend personalized antioxidant doses to avoid reductive stress and prevent adverse reproductive outcomes.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525349","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":"Bupropion, the atypical antidepressant used in smoke cessation: an in vitro study on its effects on human sperm function.","authors":"Maria Brito, Ana Gonçalves, Alberto Barros, Mário Sousa, Rosália Sá","doi":"10.1016/j.xfss.2025.02.006","DOIUrl":"10.1016/j.xfss.2025.02.006","url":null,"abstract":"<p><strong>Objective: </strong>To assess the effects of the active metabolite of Bupropion, hydroxybupropion, on human spermatozoa in vitro.</p><p><strong>Design: </strong>Laboratory based in vitro study.</p><p><strong>Patients: </strong>Human sperm samples were collected from 45 normozoospermic patients (smokers and nonsmokers).</p><p><strong>Exposure: </strong>Sperm samples were incubated at 37°C with 5% CO₂ for 2 hours with and without the IC₅₀ concentration of hydroxybupropion (1.9 μM).</p><p><strong>Main outcome measures: </strong>Several sperm analysis were performed, including vitality, motility, chromatin condensation, DNA fragmentation, oxidative stress, mitochondria membrane potential, and acrosome integrity. High-speed video microscopy and Computer-Assisted Sperm Analysis provided a detailed evaluation of sperm motility.</p><p><strong>Results: </strong>Hydroxybupropion exposure resulted in significant impairments in sperm vitality and motility, particularly in progressive motility. Chromatin condensation was significantly reduced, whereas DNA fragmentation, especially in the equatorial region, significantly increased. Mitochondria membrane potential, acrosomal integrity, and reactive oxygen species production also significantly decreased after exposure.</p><p><strong>Conclusion: </strong>The findings indicate potential harm to sperm parameters, which may contribute to infertility. Understanding how Bupropion affects reproductive function is crucial for clinicians and patients to make informed decisions regarding the use of this medication.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525335","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, Yanggang Hong","doi":"10.1016/j.xfss.2025.02.002","DOIUrl":"10.1016/j.xfss.2025.02.002","url":null,"abstract":"<p><strong>Objective: </strong>To elaborate the causal relationships between specific immunocyte phenotypes and male infertility.</p><p><strong>Design: </strong>Mendelian randomization using genome-wide association study data.</p><p><strong>Setting: </strong>Publicly available genome-wide association study data.</p><p><strong>Subjects: </strong>Large cohorts of European ancestry.</p><p><strong>Exposure: </strong>731 immunocyte phenotypes or male infertility.</p><p><strong>Main outcomes measures: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-21","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":"Prioritization of potential drug targets in ovarian-related diseases: Mendelian randomization and colocalization analyses.","authors":"Yanggang Hong","doi":"10.1016/j.xfss.2025.02.003","DOIUrl":"10.1016/j.xfss.2025.02.003","url":null,"abstract":"<p><strong>Objective: </strong>To identify key genes and potential drug targets for ovarian-related diseases through genome-wide Mendelian randomization (MR) and colocalization analyses.</p><p><strong>Design: </strong>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.</p><p><strong>Setting: </strong>Publicly available genome-wide association study data.</p><p><strong>Patients: </strong>Large cohorts of European ancestry.</p><p><strong>Exposure: </strong>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.</p><p><strong>Main outcome measures: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-21","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":"Effect of endometriosis-linked microRNAs on hepatic gene expression.","authors":"Ramanaiah Mamillapalli, Rebecca Slutzky, Anjali Mangla, Nimisha Gawde, Hugh S Taylor","doi":"10.1016/j.xfss.2025.02.001","DOIUrl":"10.1016/j.xfss.2025.02.001","url":null,"abstract":"<p><strong>Objective: </strong>To determine if microRNAs that are altered in the circulation of women with endometriosis affect metabolic gene expression in hepatic cells.</p><p><strong>Design: </strong>In vitro study.</p><p><strong>Subjects: </strong>Deidentified tissue from women with endometriosis.</p><p><strong>Intervention: </strong>MicroRNAs were used to induce or suppress target genes in hepatic cells.</p><p><strong>Main outcome measures: </strong>Effect of the microRNAs that are aberrantly expressed in endometriosis on hepatic cell gene expression using quantitative polymerase chain reaction.</p><p><strong>Results: </strong>Prior microarray studies on the serum of women with endometriosis showed differential expression of microRNAs miR-Let-7b, miR-125b-5p, miR-150-5p, and miR-3613-5p. Bioinformatic analyses revealed that these microRNAs have predicted binding sites in multiple genes involved in liver metabolism. Transfection of these miRs in HepG2 cells followed by real-time quantitative polymerase chain reaction showed that miR-Let-7b mimic increased the expression of Igfbp1 by 8-fold and reduced the expression of Mrc1 by 3.2-fold, whereas its inhibitor reduced Igfbp1 by 2.8-fold and increased Mrc1 by 5.2-fold. MiR-3613-5p mimic reduced the expression of Cyp2r1 by 2.2-fold and Mrc1 by 4-fold. MiR-125b-5p mimic increased the expression of Fabp4 by 4.1-fold, whereas miR-150-5p mimic increased the expression of Mrc1 by 1.8-fold and Cyp2r1 by 2.5-fold. Inhibitors of both miR-125b-5p and miR-150-5p did not show any effect on any of the genes.</p><p><strong>Conclusion: </strong>Circulating microRNAs, known to be aberrant in endometriosis-regulated hepatic gene expression, likely contribute to the metabolic defects seen in this disease. Treatment with miR-Let-7b and miR-3613-5p, which are downregulated in endometriosis, reversed the effect of endometriosis on the expression of IGFBP1, MRC1, and CYP2r1 genes. Therefore, miR-Let-7b and miR-3613-5p may be novel candidate therapies for endometriosis, potentially correcting the metabolic changes seen in patients with endometriosis.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461057","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":"Reviewer of the Year. F&S Science celebrates excellence in our world class reviewers","authors":"","doi":"10.1016/j.xfss.2024.10.002","DOIUrl":"10.1016/j.xfss.2024.10.002","url":null,"abstract":"","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Page 4"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382618","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":"Progesterone receptor status predicts aggressiveness of human endometriotic lesions in murine avatars","authors":"Valerie A. Flores M.D.,&nbsp;Cagdas Sahin M.D.,&nbsp;Hugh S. Taylor M.D.","doi":"10.1016/j.xfss.2024.10.004","DOIUrl":"10.1016/j.xfss.2024.10.004","url":null,"abstract":"<div><h3>Objective</h3><div>To use murine avatars for studying human endometriotic lesion response to 2 different hormonal regimens to determine whether progesterone receptor (PR) can prospectively predict response to progestin-based therapy. Endometriosis is a chronic gynecologic disease afflicting 1-in-10 reproductive-age women; however response to medical therapy is highly variable because endometriotic lesions do not consistently respond to first-line progestin-based therapy. We have previously demonstrated in a retrospective study that PR status in lesions is correlated with response to progestins. Here, we hypothesize that a prospective approach using PR status to predict response to medical will allow clinicians to individualize effective, timely treatment for this debilitating disease.</div></div><div><h3>Design</h3><div>Patient-derived xenograft murine model.</div></div><div><h3>Subjects</h3><div>Eight-week old NOD/SCID mice undergoing transplantation of endometrioma lesions collected from women undergoing surgery for endometriosis.</div></div><div><h3>Exposure</h3><div>Daily subcutaneous injections with vehicle (dimethyl sulfoxide), medroxyprogesterone acetate (MPA), or gonadotropin-releasing hormone (GnRH) antagonist, cetrorelix, for 1 month.</div></div><div><h3>Main Outcome Measures</h3><div>Lesion size 1 month after treatment.</div></div><div><h3>Results</h3><div>Lesions with high PR demonstrated a robust response to MPA compared with lesions with low PR. The mean post-MPA treatment size in high-PR lesions was sixfold smaller than that in low-PR lesions. Low-PR lesions respond far more completely to GnRH antagonist than to MPA. Surprisingly, there were differences in response to GnRH antagonist between low- and high-PR lesions. High-PR lesions responded almost completely to GnRH antagonist with a 21-fold smaller posttreatment size on average than low-PR lesions.</div></div><div><h3>Conclusions</h3><div>The use of murine avatars to test clinical response is a novel approach in endometriosis. Hormonal suppression of disease is a cornerstone of therapy; however, response is not fully predictable. We have previously shown that women with low-PR lesions respond poorly to progestin-based therapy. Here, we prospectively validate our previous work using a mouse xenograft model, demonstrating that lesions with low-PR expression do not respond to progestin-based therapy; PR status predicted response to progestin-based therapy. Moreover, PR status identifies a more aggressive form of endometriosis that is not only progesterone resistant but is also less dependent on estradiol for growth. Our findings highlight the need to develop novel nonhormonal therapies aimed at targeting the more aggressive forms of endometriosis that do not rely on the usual hormonal signals.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Pages 65-72"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407308","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}