F&S science最新文献

{"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}

{"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}

{"title":"Phthalates are detected in the follicular fluid of adolescents and oocyte donors with associated changes in the cumulus cell transcriptome","authors":"Dilan Gokyer M.D. ,&nbsp;Mary J. Laws Ph.D. ,&nbsp;Anna Kleinhans B.S. ,&nbsp;Joan K. Riley Ph.D., H.C.L.D. ,&nbsp;Jodi A. Flaws Ph.D. ,&nbsp;Elnur Babayev M.D., M.Sc.","doi":"10.1016/j.xfss.2024.10.009","DOIUrl":"10.1016/j.xfss.2024.10.009","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the follicular fluid (FF) phthalate levels in adolescents undergoing fertility preservation compared with oocyte donors and explore its association with ovarian reserve and cumulus cell (CC) gene expression.</div></div><div><h3>Design</h3><div>Retrospective study and molecular analysis of CCs and FF.</div></div><div><h3>Subjects</h3><div>Adolescents (n = 20, 16.7 ± 0.6 years) undergoing fertility preservation and oocyte donors (n = 24, 26.2 ± 0.4 years).</div></div><div><h3>Exposure</h3><div>Not applicable.</div></div><div><h3>Main Outcome Measures</h3><div>Patient demographics, ovarian stimulation, and oocyte retrieval outcomes were analyzed for each group. The FF levels of 9 phthalate metabolites were assessed individually and as molar sums representative of common compounds (all phthalates, ƩPhthalates; di(2-ethylhexyl) phthalate (DEHP)–associated phthalate metabolites, ƩDEHP), exposure sources (plastics, ƩPlastic; personal care products, ƩPCP), and modes of action (antiandrogenic, ƩAA) and compared between the 2 groups. The transcriptome of CC associated with mature oocytes was compared between adolescents and oocyte donors using bulk ribonucleic acid sequencing.</div></div><div><h3>Results</h3><div>The FF ƩPlastic and ƩPCP levels were significantly higher in adolescents than in oocyte donors. The FF ƩDEHP, ƩPlastic, ƩPCP, ƩAA, and ƩPhthalates levels were positively associated with antral follicle count in oocyte donors when adjusted for age, body mass index, and race/ethnicity. Ribonucleic acid sequencing analysis revealed 248 differentially expressed genes in CCs of adolescents within the top quartile (n = 4) of the FF ƩPhthalates levels compared with those of the adolescents within the bottom half (n = 9). Genes enriched in pathways involved in cell motility and development were significantly down-regulated.</div></div><div><h3>Conclusions</h3><div>Adolescents undergoing fertility preservation cycles demonstrate higher levels of phthalate metabolites in their FF than oocyte donors. Higher phthalate levels are associated with alterations in cumulus cells transcriptome in adolescents. The phthalate metabolite levels in FF are associated with higher antral follicle count levels in oocyte donors.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Pages 30-41"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634088","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":"Unraveling the genetic basis of azoospermia: transcriptome profiling analyses in a Greek population","authors":"Alexandra Chatziparasidou M.Sc. ,&nbsp;Theologia Sarafidou Ph.D. ,&nbsp;Maria-Anna Kyrgiafini Ph.D. ,&nbsp;Katerina Moutou Ph.D. ,&nbsp;Maria Markantoni Ph.D. ,&nbsp;Themistoklis Giannoulis Ph.D. ,&nbsp;Achilleas Papatheodorou Ph.D. ,&nbsp;Chara Oraiopoulou M.Sc. ,&nbsp;Glykeria Samolada M.Sc. ,&nbsp;Nikos Christoforidis M.D. ,&nbsp;Zissis Mamuris Ph.D.","doi":"10.1016/j.xfss.2024.10.008","DOIUrl":"10.1016/j.xfss.2024.10.008","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate whether idiopathic nonobstructive azoospermia (iNOA) has its own transcriptomic signature.</div></div><div><h3>Design</h3><div>Testicular tissue biopsies were retrieved, processed, and prepared for ribonucleic acid (RNA) extraction from 26 consented patients diagnosed with iNOA. Samples were grouped into four pools based on the presence of testicular spermatozoa: two replicate pools for “No presence” (Null-spz-1 and Null-spz-2 pools), one for “High presence” (High-spz pool), and one for “Rare presence” (Rare-spz pool). A second set of replicate pools (CF-1 and CF-2) were used from patients with obstructive azoospermia (OA) and served as controls. RNA sequencing (RNA-seq) and comparative transcriptomics analysis were performed, followed by differential gene expression analysis focused on protein-coding genes only. Differentially expressed genes (DEGs) exclusively upregulated or downregulated were further analyzed using the Gene Ontology (GO), STRING, and Kyoto Encyclopedia of Genes and Genome bioinformatic platforms.</div></div><div><h3>Subjects</h3><div>Males in whom iNOA was diagnosed.</div></div><div><h3>Exposure</h3><div>Testicular biopsies from men in whom iNOA was diagnosed.</div></div><div><h3>Main Outcome Measures</h3><div>Protein-coding DEGs.</div></div><div><h3>Results</h3><div>A significantly altered transcriptomic profile of protein-coding genes was identified in the testicular tissues from men with iNOA. A total of 3,858 genes exhibited dysregulated expression, with 1,994 genes being exclusively downregulated and 1,734 upregulated. Biological processes such as male gamete generation (GO:0048232) and meiotic cycle (GO:0051321) were significantly enriched by the downregulated DEGs whereas the upregulated DEGs enriched BPs such as regulation of cell death (GO:0010941), regulation of cell adhesion (GO:0030155), and defense response (GO:0006952). Interactome analysis identified hub genes among the downregulated DEGs, including PCNA, PLK1, MCM4, CDK1, CCNB1, AURKA, CCNA2, and CDC6, and among the upregulated DEGs, including EGFR, RELA, CTNNB1, MYC, JUN, SMAD3, STAT3 NFKB1, TGFB1, and ACTB. In addition, Kyoto Encyclopedia of Genes and Genome analysis demonstrated that pathways such as cell cycle (hsa04110) and oocyte meiosis (hsa04114) are primarily affected by the downregulated genes, whereas the upregulated genes mainly affected pathways such as the focal adhesion (hsa04510) and the PI3-Akt signaling pathway (hsa04151).</div></div><div><h3>Conclusion</h3><div>A distinct messenger RNA expression profile and altered transcriptomic activity were identified in the testicular tissues of men with iNOA.</div></div><div><h3>Clinical Trial Registration Number</h3><div>University of Thessaly 1, 15.04.2016 and the Greek National Authority 701/15.9.2017.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Pages 16-29"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634099","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":"Sphingosine 1-phosphate acts as proliferative and fibrotic cue in leiomyoma cells","authors":"Margherita Rossi M.Sc. ,&nbsp;Isabelle Seidita Ph.D. ,&nbsp;Matteo Prisinzano M.Sc. ,&nbsp;Maryam Raeispour M.Sc. ,&nbsp;Lucia Romeo M.Sc. ,&nbsp;Flavia Sorbi M.D. ,&nbsp;Massimiliano Fambrini M.D. ,&nbsp;Pasquapina Ciarmela Ph.D. ,&nbsp;Felice Petraglia M.D. ,&nbsp;Caterina Bernacchioni Ph.D. ,&nbsp;Chiara Donati Ph.D.","doi":"10.1016/j.xfss.2024.11.003","DOIUrl":"10.1016/j.xfss.2024.11.003","url":null,"abstract":"<div><h3>Objective</h3><div>To determine whether the bioactive sphingolipid sphingosine 1-phosphate (S1P) modulates cellular proliferation and synthesis of fibrotic proteins in leiomyoma differently than myometrial cells.</div></div><div><h3>Design</h3><div>A basic science study using human leiomyoma and myometrial cells.</div></div><div><h3>Subjects</h3><div>Not applicable. This is an in vitro study performed on cellular models.</div></div><div><h3>Exposure</h3><div>Leiomyoma and myometrial cells were treated with S1P, as well as with selective antagonists for S1P-specific G protein–coupled receptors and secondarily with inhibitors of extracellular signal-regulated kinase 1/2 (ERK1/2) and ezrin.</div></div><div><h3>Main Outcome Measures</h3><div>The main outcome measures included cellular proliferation and fibrogenesis. Bromodeoxyuridine Cell Proliferation Assay was employed to measure deoxyribonucleic acid synthesis and proliferation, whereas western blot analysis was used to assess the expression of the fibrotic markers N-cadherin, α-smooth muscle actin, transgelin, and collagen type I alpha 1.</div></div><div><h3>Results</h3><div>Sphingosine 1-phosphate stimulates cellular proliferation of leiomyoma but not myometrial cells. The mitogenic effect elicited by S1P relies on the engagement of its specific receptor S1P₂ and is mediated by ERK1/2 and ezrin activation. Furthermore, S1P exerts a profibrotic effect in a S1P-specific G protein–coupled receptor–dependent manner in leiomyoma but not myometrial cells.</div></div><div><h3>Conclusions</h3><div>These results, besides extending the knowledge on the molecular mechanism underlying uterine leiomyoma development and fibrosis, demonstrate the pathogenetic role of S1P in leiomyoma and support the rationale for targeting S1P signaling pathway as innovative potential treatment.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Pages 99-106"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792888","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}

{"title":"A positive ReceptivaDx result for BCL6 does not correlate with abnormal ERA results or decreased expression of receptivity-associated markers: two sides of the endometrial receptivity coin in fertility evaluation and treatment","authors":"David Huang M.D. ,&nbsp;Emily Flynn Ph.D ,&nbsp;Ana Almonte-Loya B.S. ,&nbsp;Brittany Davidson B.S. ,&nbsp;Meagan Chan D.N.P. ,&nbsp;Amber Casillas B.S. ,&nbsp;Juan C. Irwin M.D., Ph.D. ,&nbsp;Gabriela K. Fragiadakis Ph.D. ,&nbsp;Hakan Cakmak M.D. ,&nbsp;Alexis J. Combes Ph.D. ,&nbsp;Marcelle I. Cedars M.D. ,&nbsp;Marina Sirota Ph.D. ,&nbsp;Linda C. Giudice M.D., Ph.D.","doi":"10.1016/j.xfss.2024.10.005","DOIUrl":"10.1016/j.xfss.2024.10.005","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To investigate if a positive result on ReceptivaDx for evaluation of B-cell lymphoma 6 (BCL6), a proposed marker of progesterone resistance associated with impaired uterine receptivity, correlates with a suboptimal profile of receptivity-associated markers in the window of implantation using the endometrial receptivity array and single-nucleus transcriptomic analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;Retrospective clinical cohort study; pilot study of single-nucleus RNA sequencing of prospectively collected window of implantation endometrium undergoing ReceptivaDx BCL6 evaluation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Subjects&lt;/h3&gt;&lt;div&gt;Patients with infertility who underwent endometrial biopsy for concurrent endometrial receptivity array analysis (ERA; Igenomix, Valencia, Spain) and BCL6 immunostaining (ReceptivaDx; Cicero Diagnostics, Inc., Huntington Beach, CA).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Exposure&lt;/h3&gt;&lt;div&gt;Positive BCL6 result on ReceptivaDx (histologic score &gt;1.4).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;Prereceptive ERA result; relative expression levels of endometrial receptivity-associated epithelial genes by single-nucleus sequencing.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;One hundred and seventy-two patients with concurrent ERA and ReceptivaDx evaluation were included in the analysis: 40 were BCL6-positive and 132 were BCL6-negative. One patient (2.5%) in the BCL6-positive group had a prereceptive ERA result, compared with 29 patients (22.0%) in the BCL6-negative group (&lt;em&gt;P&lt;/em&gt;&lt;.01). BCL6 positivity was associated with decreased odds of a prereceptive ERA result (odds ratio, 0.09; 95% confidence interval, 0.01–0.69; &lt;em&gt;P&lt;/em&gt;=.02). Single-nucleus transcriptomic analysis of 5,718 epithelial cell nuclei from four individuals showed significant cell type-specific transcriptomic changes associated with a positive ReceptivaDx BCL6 result in both natural cycle (NC) and programmed cycle (PC) endometrium: there were 2,801 significantly differentially expressed genes comparing NC BCL6-positive with -negative, and 1,062 differentially expressed genes comparing PC BCL6-positive with -negative. Of the 34 receptivity-associated epithelial markers evaluated, 16 were significantly upregulated in NC BCL6-positive vs. -negative endometrium epithelial nuclei. In PC epithelial nuclei, 12 of the 34 receptivity-associated genes were significantly upregulated, whereas only one was significantly downregulated in BCL6-positive vs. -negative endometrium.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;A positive ReceptivaDx BCL6 result does not correlate with a prereceptive ERA. Epithelial cells from BCL6-positive endometrium did not show significantly decreased expression in most of the receptivity markers evaluated. These findings demonstrate discordance between the interpretation of “endometrial receptivity” by ReceptivaDx and ERA, and highlight the need for further validation of endometrial evaluation methods in fertility treatment.&lt;/div&gt;&lt;/d","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Pages 55-64"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482284","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":"Bleomycin in vitro exposure decreases markers of human male gamete competence","authors":"Ana Lobo de Almeida M.Sc. ,&nbsp;Ana Gonçalves M.Sc. ,&nbsp;Alberto Barros M.D., Ph.D. ,&nbsp;Mário Sousa M.D., Ph.D. ,&nbsp;Rosália Sá M.D., Ph.D.","doi":"10.1016/j.xfss.2024.10.003","DOIUrl":"10.1016/j.xfss.2024.10.003","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the in vitro impact of bleomycin on human sperm deoxyribonucleic acid (DNA) integrity, functionality, and morphology, with the aim of elucidating the underlying mechanism and anticipating potential repercussions on patients’ reproductive function.</div></div><div><h3>Design</h3><div>Controlled laboratory-based in vitro investigation.</div></div><div><h3>Subjects</h3><div>Surplus human ejaculate donated for research by 45 reproductive-age participants exhibiting normozoospermic sperm parameters after clinical semen analysis. None of the participants had received a cancer diagnosis or undergone radiotherapy, chemotherapy, or both.</div></div><div><h3>Exposure</h3><div>After clinical semen analysis, sperm samples were centrifuged, diluted in sperm preparation medium, and exposed to bleomycin (100 μg/mL) for 2 hours at 37 °C in a humidified incubator with 5% CO₂.</div></div><div><h3>Main Outcome Measures</h3><div>In vitro human sperm competence was evaluated by comparing raw sperm, sperm incubated with sperm preparation medium, and sperm exposed to bleomycin. Competence indicators included sperm motility, vitality, DNA and acrosome integrity, and mitochondrial membrane potential. Transmisson electron microscopy was employed to correlate the ultrastructural morphological findings with functional assays.</div></div><div><h3>Results</h3><div>Exposure to bleomycin for 2 hours in vitro significantly decreased sperm vitality, motility, and chromatin condensation compared with raw and control sperm. It also significantly increased sperm DNA fragmentation and the proportion of sperm with low mitochondrial membrane potential. Additionally, bleomycin significantly retarded the acrosomal response compared with control but did not affect the formation of intracellular and extracellular reactive oxygen species. Bleomycin-induced ultrastructural morphological changes supported the detected functional alterations.</div></div><div><h3>Conclusions</h3><div>Bleomycin negatively impacts male gamete competency in humans. Healthcare professionals should vigilantly monitor and further investigate the gonadotoxicity effects of bleomycin, in addition to its recognized lung toxicity. Meanwhile, it is recommended that patients with cancer undergoing bleomycin-containing chemotherapy regimens receive guidance on fertility preservation strategies.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Pages 5-15"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407307","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}