F&S science最新文献

{"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}

{"title":"Blood-based inflammatory markers in female infertility: evidence from Mendelian randomization analysis","authors":"Simon Alesi B.Med.Sc. (Hons) ,&nbsp;Helena Teede Ph.D. ,&nbsp;Joanne Enticott Ph.D. ,&nbsp;Kushan De Silva Ph.D. ,&nbsp;Aya Mousa Ph.D.","doi":"10.1016/j.xfss.2024.11.001","DOIUrl":"10.1016/j.xfss.2024.11.001","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate causal associations between blood-based inflammatory markers and female infertility using Mendelian randomization (MR).</div></div><div><h3>Design</h3><div>Mendelian randomization using genome-wide association study data.</div></div><div><h3>Subjects</h3><div>Large female-only cohorts of European ancestry.</div></div><div><h3>Exposure</h3><div>Blood-based inflammatory markers (C-reactive protein, interleukins, monocyte chemoattractant protein-1, tumor necrosis factor-α, interferon-γ).</div></div><div><h3>Main Outcome Measures</h3><div>Anovulatory infertility (1,054 cases and 117,098 controls); female infertility of other/unspecified origin (5,667 cases and 117,098 controls); and medical treatment for female infertility (2,706 cases and 120,873 controls). Total causal effects were assessed using univariable two-sample methods including inverse variance weighted (IVW) as the primary analysis, as well as other secondary analyses (MR-Egger, weighted median, etc.), with relevant quality assessments.</div></div><div><h3>Results</h3><div>Interleukin-8 demonstrated a positive association with anovulatory infertility via IVW (odds ratio, 95% confidence interval; 1.51, 1.04–2.21) and weighted median (1.64, 1.05–2.57) methods. Monocyte chemoattractant protein-1 was associated with anovulatory infertility via MR-Egger (2.06, 1.13–3.77). Inverse associations were found for interleukins-12 and -18 via IVW, with higher interleukin-12 being associated with lower medical treatment for female infertility (0.75, 0.59–0.94), whereas higher interleukin-18 was associated with lower female infertility of other/unspecified origin (0.90, 0.83–0.97).</div></div><div><h3>Conclusions</h3><div>This is the first study to examine causal relationships between inflammation and female infertility using MR. Monocyte chemoattractant protein-1 and interleukin-8 are implicated in anovulatory infertility; however, only the relationship with interleukin-8 was evident in the primary analysis. Interleukins-12 and -18 demonstrated inverse associations with infertility outcomes. Further research is needed to uncover the mechanistic functions of these markers to confirm causality and examine their therapeutic potential for female infertility.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Pages 85-98"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633943","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":"Polycystic ovary syndrome and morphokinetic embryonic development: a case-control study evaluating 791 embryos.","authors":"Gilad Karavani, Shira Shapira-Nass, Natali Schachter-Safrai, Tal Imbar, Assaf Ben-Meir","doi":"10.1016/j.xfss.2025.01.003","DOIUrl":"10.1016/j.xfss.2025.01.003","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the association between polycystic ovary syndrome (PCOS) and the rate of embryo development, using time-lapse monitoring systems, compared with a control group of women with mechanical (tubal) factor infertility.</p><p><strong>Design: </strong>A retrospective case-control study conducted in a university-affiliated in vitro fertilization (IVF) unit.</p><p><strong>Patients: </strong>Women with PCOS undergoing IVF treatments and those with non-PCOS controls with tubal factor infertility only. Development morphokinetic milestones were compared and analysis of covariance for time to distinct cell number as well as logistic mixed models to determine predictors for embryos over the 75th percentile was performed.</p><p><strong>Exposure: </strong>Not applicable.</p><p><strong>Main outcome measures: </strong>Embryo development morphokinetic parameters in women with and without PCOS undergoing IVF treatments.</p><p><strong>Results: </strong>The study included 791 embryos from 115 women, 364 embryos from 52 women with PCOS and 427 embryos from 63 women with non-PCOS controls with tubal factor infertility. The PCOS group was 4 years younger (30.07 ± 6.03 vs. 34.08 ± 4.84 years) and had higher number of oocytes retrieved (16.00 vs. 11.00), mature oocytes (11.00 vs. 7.00) and fertilized oocytes (8.00 vs. 5.00). The PCOS and control groups demonstrated comparable clinical pregnancy rates (55.8% vs. 32.1%), miscarriage rate (12.5% vs. 11.8%), and live birth rate (48.8% vs. 31.2%). Morphokinetic parameters were comparable between the groups. Although age was associated with later time to 5 and 8 discrete cells and start of blastulation (tSB), PCOS was only associated with later tSB, including tSB >75th percentile.</p><p><strong>Conclusion: </strong>This study demonstrated comparable IVF outcomes in women with PCOS and non-PCOS controls. An analysis of time-lapse monitoring data from these patients showed no evidence that PCOS negatively affects embryonic development rate in women undergoing IVF cycles.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017331","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":"Enhanced ovarian FKBP51 expression is associated with ovarian aging: a molecular insight for age-related fertility in women.","authors":"Papri Sarkar, Monica Moore, Asli Ozmen, Busra Cetinkaya-Un, Vitko Julie, Anthony N Imudia, Charles J Lockwood, Umit A Kayisli, Ozlem Guzeloglu-Kayisli","doi":"10.1016/j.xfss.2025.01.004","DOIUrl":"10.1016/j.xfss.2025.01.004","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;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 (Fkbp5&lt;sup&gt;+/+&lt;/sup&gt;) and Fkbp5 knockout (Fkbp5&lt;sup&gt;-/-&lt;/sup&gt;) mice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Laboratory-based experimental study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Subjects: &lt;/strong&gt;Samples collected included follicular fluid, CCs, GCs, and serum from group 1: young women with normal ovarian reserve (&lt;35 years; n = 12); group 2: DOR (antimüllerian hormone &lt;1 ng/mL; n = 10); and group 3: women of advanced age with normal ovarian reserve (&gt;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 Fkbp5&lt;sup&gt;+/+&lt;/sup&gt;and Fkbp5&lt;sup&gt;-/-&lt;/sup&gt; mice. All the experiments were performed at an academic-affiliated assisted reproductive technology unit/laboratory.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Exposure: &lt;/strong&gt;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 Fkbp5&lt;sup&gt;+/+&lt;/sup&gt;and Fkbp5&lt;sup&gt;-/-&lt;/sup&gt; mice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcome measures: &lt;/strong&gt;(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 Fkbp5&lt;sup&gt;+/+&lt;/sup&gt; and Fkbp5&lt;sup&gt;-/-&lt;/sup&gt; old mice ovaries. Serum and follicular fluid levels of transforming growth factor β1, and soluble endoglin measured by enzyme-linked immunosorbent assay.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;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; P=.002). Stronger Picrosirius Red staining, suggestive of fibrosis, was seen in ovarian stromal tissue of postmenopausal vs. premenopausal women (54.06 ± 6.94 vs. 37.50 ± 14.29; P=.02). Analysis of qPCR revealed that (1) Col1a1, Col1a2, Col3a1 levels were significantly lower in ovaries obtained from 14-month-old Fkbp5&lt;sup&gt;-/-&lt;/sup&gt; vs. Fkbp5&lt;sup&gt;+/+&lt;/sup&gt; mice","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-19","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":"Chemotherapy-induced diminished murine ovarian reserve model and impact of low-dose chemotherapy on fertility.","authors":"Lara Houeis, Graziella van der Plancke, Jen-Yu Wen, Laurence Dupuy, Elodie Kara, Luciana Cacciottola, Marie-Christine Maurel, Jacques Donnez, Marie-Madeleine Dolmans","doi":"10.1016/j.xfss.2025.01.002","DOIUrl":"10.1016/j.xfss.2025.01.002","url":null,"abstract":"<p><strong>Objective: </strong>To establish a murine model of chemotherapy-induced diminished ovarian reserve (DOR) and investigate residual fertility after chemotherapy exposure.</p><p><strong>Design: </strong>Two different chemotherapy protocols were tested to establish a valid DOR model by comparing follicle densities in mice given either protocol or physiological solution. An ovarian stimulation protocol was then selected from among different gonadotropins by counting the number of day 2 embryos obtained from normal mice. Finally, DOR mice were stimulated 5 and 8 weeks after chemotherapy with the chosen gonadotropin protocols, and day 2 embryos were recovered after mating, as was ovarian tissue for further immunohistologic analyses.</p><p><strong>Subjects: </strong>Seventy-two Naval Medical Research Institute mice.</p><p><strong>Exposure: </strong>Two different chemotherapy protocols.</p><p><strong>Main outcome measures: </strong>This study compared day 2 embryo counts in both normal and chemotherapy-induced DOR mice. Ovarian histology and morphology were also investigated by follicle counting and classification, as was immunostaining for apoptosis (cleaved caspase-3), activation (phospho-Akt), and proliferation (Ki67).</p><p><strong>Results: </strong>A dose of 12 mg/kg of busulfan (Bu) + 120 mg/kg of cyclophosphamide (Cy) was chosen to establish the DOR model as it significantly reduced the ovarian reserve compared to both control mice (physiological solution) and the 1.2 mg/kg of Bu + 12 mg/kg of Cy protocol, without depleting it completely. When stimulated with 3.75 IU of Menopur, normal mice produced significantly more embryos than DOR mice given 12 mg/kg of Bu + 120 mg/kg of Cy (41.40 ± 14.74 vs. 23.67 ± 15.55 day 2 embryos). Although the follicle count was statistically diminished after single-dose chemotherapy administration, the remaining follicles did not display any difference in terms of apoptosis, activation, or proliferation rates.</p><p><strong>Conclusion: </strong>We successfully established a chemotherapy-induced DOR model using 12 mg/kg of Bu + 120 mg/kg of Cy, as evidenced by lower, but not completely depleted, follicle numbers and fewer retrieved embryos. Histologic study of ovarian tissue exposed to DOR-inducing chemotherapy revealed that surviving follicles were of the similar quality as tissue not exposed to chemotherapy.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973627","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}