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Compressive force induces differential gene and protein expression in uterine fibroids. 压缩力诱导子宫肌瘤差异基因和蛋白表达。
F&S science Pub Date : 2025-07-22 DOI: 10.1016/j.xfss.2025.07.004
Carolyn A Nietupski, Megan R Sax, Rose Dean, Andreja Moset Zupan, Emily G Hurley, Stacey C Schutte
{"title":"Compressive force induces differential gene and protein expression in uterine fibroids.","authors":"Carolyn A Nietupski, Megan R Sax, Rose Dean, Andreja Moset Zupan, Emily G Hurley, Stacey C Schutte","doi":"10.1016/j.xfss.2025.07.004","DOIUrl":"10.1016/j.xfss.2025.07.004","url":null,"abstract":"<p><strong>Objective: </strong>To study how compressive forces influence fibroid and myometrial cells. Our work aimed to identify proteins and signaling pathways that are altered in fibroids in response to compressive forces.</p><p><strong>Design: </strong>Laboratory-based.</p><p><strong>Subjects: </strong>Patient-matched fibroid and myometrial cells were isolated from five women undergoing hysterectomy or myomectomy for the treatment of uterine fibroids. Only samples from women who had not had hormonal modulation within 3 months of surgery were used for this study. An embedded spheroid model was developed to model the fibroid tissue and provide a cushion that would help with the distribution of compressive force.</p><p><strong>Exposure: </strong>Weights, 0 or 6.4 mm Hg, were added on top of an agarose cushion. Spheroids were cultured for 7 days.</p><p><strong>Main outcome measures: </strong>Histological evaluation, RNA-sequencing (n = 5), and proteomics characterization (n = 3). Paired multi-test t-tests were performed for statistical analysis. Differentially expressed genes (DEGs) were considered clinically relevant if the same genes were also significantly differentially expressed in at least one of the four existing fibroid and myometrium RNA-sequencing datasets.</p><p><strong>Results: </strong>A total of 61 clinically relevant DEGs were identified between cell types that were only differentially expressed when the spheroids were under compression. This included EPHB1 which encodes ephrin signaling receptor EphB1; it was upregulated log2 fold-change of 2.81 in fibroid cells (q = 5.35 × 10<sup>-3</sup>). Compression led to the enrichment of genes involved in extracellular matrix (ECM) organization; however, the genes varied between the cell types. At the protein level, myometrial spheroids had alterations in proteins associated with uterine fibroids (q = 1.00 × 10<sup>-33</sup>). There were alterations in collagen abundance in fibroid spheroids, but not collagen 1, although the collagenase MMP-1 was significantly lower in fibroid spheroids. Enrichment analysis identified ECM-receptor interactions as enriched in compression-induced changes between the cell types.</p><p><strong>Conclusions: </strong>Compressive forces must be considered to study some of the important differences between fibroids and myometrium, including ephrin signaling. Enrichment analysis of the proteins with different abundances suggests that compression may also be involved in fibroid tumor initiation.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710108","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}
引用次数: 0
Artificial intelligence-driven oocyte assessment for predicting blastulation and high-quality blastocyst formation in severe male factor infertility. 人工智能驱动的卵母细胞评估用于预测严重男性因素不育的囊胚形成和高质量囊胚形成。
F&S science Pub Date : 2025-07-15 DOI: 10.1016/j.xfss.2025.07.003
Edson Borges, Daniela Braga, Maite Del Collado, Assumpto Iaconelli, Jullin Fjeldstad, Natalie Mercuri, Parisa Mojiri, Amanda Setti
{"title":"Artificial intelligence-driven oocyte assessment for predicting blastulation and high-quality blastocyst formation in severe male factor infertility.","authors":"Edson Borges, Daniela Braga, Maite Del Collado, Assumpto Iaconelli, Jullin Fjeldstad, Natalie Mercuri, Parisa Mojiri, Amanda Setti","doi":"10.1016/j.xfss.2025.07.003","DOIUrl":"10.1016/j.xfss.2025.07.003","url":null,"abstract":"<p><strong>Objective: </strong>To study whether artificial intelligence (AI)-driven oocyte evaluation is associated with blastocyst development and quality in couples with severe male factor infertility (SMF) undergoing intracytoplasmic sperm injection (ICSI) cycles.</p><p><strong>Design: </strong>Cohort study.</p><p><strong>Subjects: </strong>Fourteen thousand six hundred two oocyte images from 2,156 ICSI cycles performed between January 2020 and May 2024 in a private, university-affiliated in vitro fertilization center. Cycles were categorized into the following two groups: SMF (n = 200 cycles, 1,478 embryos) and non-SMF (n = 1,956 cycles, 13,124 embryos). Severe male factor infertility was defined as <5 million sperm in the ejaculate.</p><p><strong>Exposure: </strong>Oocyte images were captured before ICSI and scored using the AI tool MAGENTA. The predictive value of Magenta Scores (MS) on embryonic development was assessed. The association between MS and oocyte fertilization and blastocyst formation was analyzed.</p><p><strong>Main outcome measures: </strong>Oocyte fertilization, blastulation rate, and blastocyst quality.</p><p><strong>Results: </strong>Magenta scores were significantly lower in oocytes that failed to fertilize compared with those that successfully fertilized (5.00 ± 0.04 vs. 6.44 ± 0.03). Blastulation rate was lower in the SMF group (46.61% vs. 50.80%), and blastocysts exhibited higher MS than nonblastocysts (5.12 ± 0.3 vs. 6.69 ± 0.3). The top-quality blastocyst rate was lower in SMF (56.6% vs. 65.2%), and high-quality blastocysts had higher MS than lower-quality ones (7.2 ± 0.6 vs. 6.8 ± 0.5). Among SMF cycles, MS were lower in oocytes that failed to fertilize (4.91 ± 0.12 vs. 6.34 ± 0.10). Magenta scores also differed between embryos that reached the blastocyst stage and those that did not (6.70 ± 0.11 vs. 4.96 ± 0.10). Top-quality blastocysts had significantly higher MS than others (7.00 ± 0.21 vs. 6.39 ± 0.19). Paternal age negatively correlated with fertilization, blastulation, and blastocyst quality; however, differences remained significant after adjusting for paternal age.</p><p><strong>Conclusion: </strong>Artificial intelligence-based oocyte evaluation is associated with fertilization, blastulation, and blastocyst quality in SMF couples undergoing ICSI cycles. Magenta score values were consistently higher for blastocysts than nonblastocysts, demonstrating the AI tool's utility in identifying oocytes with greater developmental potential, regardless of male infertility factors. However, the absence of sperm-specific factors in the MAGENTA algorithm may limit its ability to fully account for male infertility.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661170","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}
引用次数: 0
Transcriptome landscapes induced by estetrol, estradiol, and ethinylestradiol in primary human endometriotic stromal cells. 在原发性人子宫内膜异位症基质细胞中由雌二醇、雌二醇和乙炔雌二醇诱导的转录组景观。
F&S science Pub Date : 2025-06-25 DOI: 10.1016/j.xfss.2025.06.002
Marie Nakajima, Gentaro Izumi, Kaori Koga, Vita Silvana, Mohammed Elsherbini, Atsushi Okumura, Michihito Wada, Satoru Yamanaka, Yasushi Hirota, Yutaka Osuga
{"title":"Transcriptome landscapes induced by estetrol, estradiol, and ethinylestradiol in primary human endometriotic stromal cells.","authors":"Marie Nakajima, Gentaro Izumi, Kaori Koga, Vita Silvana, Mohammed Elsherbini, Atsushi Okumura, Michihito Wada, Satoru Yamanaka, Yasushi Hirota, Yutaka Osuga","doi":"10.1016/j.xfss.2025.06.002","DOIUrl":"10.1016/j.xfss.2025.06.002","url":null,"abstract":"<p><strong>Objective: </strong>To compare the transcriptomes induced by estrogens used in combined oral contraceptives (COCs): estetrol (E4), ethinylestradiol (EE), and estradiol (E2) in human primary endometriotic stromal cells.</p><p><strong>Design: </strong>Endometriotic stromal cells were cultured in the presence of E4 (10<sup>-6</sup> mol/L), E2 (10<sup>-8</sup> mol/L) or EE (10<sup>-9</sup> mol/L) for 24 hours. Transcriptomes induced by E4 were compared with those induced by E2 and EE.</p><p><strong>Subjects: </strong>Endometriotic stromal cells were obtained from patients with ovarian endometriomas.</p><p><strong>Main outcome measures: </strong>Transcriptomes were examined using RNA sequencing analysis, and messenger RNA levels were measured using reverse transcription-quantitative polymerase chain reaction.</p><p><strong>Results: </strong>Estetrol treatment resulted in 114 differentially expressed genes compared with the control (|log2fold change| >0.2). The number was higher than those differentially expressed between E4 and E2 (82 genes) and between E4 and EE (75 genes). Of the differentially expressed genes between E4 and the control, 79% (90 genes) changed in the same manner as in EE and E2. In contrast, 21% (24 genes) of the genes changed in an E4-preferential manner.</p><p><strong>Conclusion: </strong>The present study elucidated that although E4 induces the expression of specific unique genes in endometriotic stromal cells distinct from those regulated by other estrogens, the overall gene expression profile is largely analogous to that induced by other estrogens. When differences in progestin are not considered, it is suggested that the COC containing E4 exhibits effects on endometriosis comparable with those of other COCs.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512883","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}
引用次数: 0
Impact of a microfluidic-based selection device on sperm deoxyribonucleic acid fragmentation and intracytoplasmic sperm injection cycles. 基于微流体的选择装置对精子DNA断裂和icsi周期的影响。
F&S science Pub Date : 2025-05-19 DOI: 10.1016/j.xfss.2025.05.002
Maria Luisa Pardiñas, Rocío Rivera-Egea, Jose Maria de Los Santos, Carmen Vidal, Juan Giles, David Ortega-Jaen, Julia Gil, Angel Martin, Thamara Viloria, Maria Jose de Los Santos
{"title":"Impact of a microfluidic-based selection device on sperm deoxyribonucleic acid fragmentation and intracytoplasmic sperm injection cycles.","authors":"Maria Luisa Pardiñas, Rocío Rivera-Egea, Jose Maria de Los Santos, Carmen Vidal, Juan Giles, David Ortega-Jaen, Julia Gil, Angel Martin, Thamara Viloria, Maria Jose de Los Santos","doi":"10.1016/j.xfss.2025.05.002","DOIUrl":"10.1016/j.xfss.2025.05.002","url":null,"abstract":"<p><strong>Objective: </strong>To determine the impact of a microfluidic-based sperm selection device on sperm parameters and embryo variables compared with the conventional swim-up method in sibling oocytes.</p><p><strong>Design: </strong>Prospective observational study.</p><p><strong>Subjects: </strong>A total of 345 oocytes were recruited from 27 couples undergoing intracytoplasmic sperm injection, including both own (n = 195) and donation (n = 150) cycles. None of the patients presented severe male factor.</p><p><strong>Intervention/exposure: </strong>Semen sample was divided into 2 groups and processed using swim-up or the microfluidic sperm selection device (MSSD) ZyMōt. Half of the oocytes were inseminated with swim-up-selected spermatozoa, and the rest were inseminated with MSSD-selected spermatozoa. Embryo development was followed by time-lapse. Sperm deoxyribonucleic acid (DNA) fragmentation was measured using the sperm chromatin dispersion test, analyzed with ImageJ. A Mann-Whitney U test was performed for statistical analysis.</p><p><strong>Main outcome measures: </strong>Sperm DNA fragmentation levels, sperm parameters, fertilization rates, embryo morphokinetics, and rate of usable blastocysts.</p><p><strong>Results: </strong>Sperm DNA fragmentation was significantly lower in the MSSD group than in the swim-up group (20.3% vs. 11%), indicating a better selection. Analyzing separately the oocytes from the patient's own cycles, MSSD showed a significantly higher rate of usable blastocysts per fertilized oocyte. However, this difference was not observed using donated oocytes or when both cycles were combined. Embryos from the swim-up group showed a significant delay in time of pronuclear appearance and morula formation compared with those from the MSSD group, being more marked in donated oocytes. No significant differences were observed in the fertilization rate and the remaining morphokinetic times.</p><p><strong>Conclusion: </strong>This study provides valuable information on the use of MSSD for noninvasive sperm selection. When MSSD was used, we observed a reduction in sperm DNA fragmentation and an enhancement in the number of usable embryos in our own cycles. These findings could be compatible with a reduced capacity to repair sperm damage due to poorer oocyte quality caused by advanced age.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121521","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}
引用次数: 0
A sound approach for ova denudation 一种治疗卵子剥落的良好方法。
F&S science Pub Date : 2025-05-01 DOI: 10.1016/j.xfss.2024.12.005
Amir Mokhtare Ph.D. , Amirhossein Favakeh M.S. , Philip Xie B.Sc. , Zev Rosenwaks M.D. , Alireza Abbaspourrad Ph.D. , Gianpiero Palermo M.D., Ph.D.
{"title":"A sound approach for ova denudation","authors":"Amir Mokhtare Ph.D. ,&nbsp;Amirhossein Favakeh M.S. ,&nbsp;Philip Xie B.Sc. ,&nbsp;Zev Rosenwaks M.D. ,&nbsp;Alireza Abbaspourrad Ph.D. ,&nbsp;Gianpiero Palermo M.D., Ph.D.","doi":"10.1016/j.xfss.2024.12.005","DOIUrl":"10.1016/j.xfss.2024.12.005","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To introduce an innovative noncontact method for denudation process of cumulus-oocyte complexes (COCs) for intracytoplasmic sperm injection (ICSI).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;We designed and fabricated novel acoustohydrodynamic tweezers (AHTs) to perform contactless denudation and tested them in a mouse model. Cumulus removal efficiency, preimplantation development, and live birth were assessed and compared with those in conventional manual pipetting (MP) denudation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Subjects&lt;/h3&gt;&lt;div&gt;Fourteen female B6D2F1/J mice (approximately 4 weeks of age), nine male B6D2F1/J mice (6–12 weeks of age), and 28 CD-1 female mice (approximately 6 weeks of age) were used for experiment.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Exposure&lt;/h3&gt;&lt;div&gt;We designed a contactless platform for oocyte denudation on the basis of the principle of focalized acoustic waves. We first investigated the acoustic intensity and thermal variability by measuring the surface displacement and temperature with a thermal camera to ensure a safe operation. Cumulus-oocyte complexes were denuded by conventional MP with 40 IU/mL of hyaluronidase serving as control or by AHTs with a reduced amount of hyaluronidase (15 IU/mL). Piezo-ICSI was performed on both experimental and control groups. A triplicate of denudation and insemination experiments was performed. All embryos were monitored in a time-lapse incubator. Embryo developmental rates were compared by the chi-square test. Embryo morphokinetic timing as a continuous variable was compared by 1-way analysis of variance. Embryo transfers were performed on some blastocysts.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;The procedural time for each denudation method was measured and compared. Fertilization, embryo development and morphokinetics, pregnancy, and live birth rate were compared between the control and experimental cohorts.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Facile noncontact denudation was achieved without any damage to oocyte. Acoustic induced fluidic shear was the main contributor to COC denudation. The average denudation time per oocyte decreased by 46% (15 seconds per oocyte for control vs. 8 seconds per oocyte for AHT) while using a lower concentration of hyaluronidase. Piezo-ICSI on oocytes processed by MP and AHTs resulted in comparable rates of survival (86.1% vs. 85.3%), fertilization (96.7% vs. 94.1%), and blastocyst (88.0% vs. 81.3%). Embryo morphokinetics for both experimental and control cohorts were comparable, showing no impact of sound waves on the embryo development. Eventual delivery rates were also comparable between the MP and AHT cohorts (51.3% vs. 55.4%).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Acoustohydrodynamic tweezers are used for contactless removal of the cumulus cells from the COCs before ICSI in an expedited, safe, and reliable manner. Embryo development outcomes confirm their safety and validate their potential for a comprehensive ICSI-on-chip device.&lt;/div&gt;&lt;/div","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 118-125"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904281","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}
引用次数: 0
Luteinizing hormone receptor deficiency in immature cumulus-oocyte complexes retrieved for assisted reproduction 促黄体生成素受体缺乏在未成熟的卵母细胞复合体检索辅助生殖。
F&S science Pub Date : 2025-05-01 DOI: 10.1016/j.xfss.2024.12.006
Maíra Casalechi Ph.D., Maria Thereza V. Pereira M.Sc., Wiviane A. Assis Ph.D., Cynthia Dela Cruz Ph.D., Tays F. Guedes B.Sc., Ines Katerina Cavallo M.D., Ph.D., Fernando M. Reis M.D., Ph.D.
{"title":"Luteinizing hormone receptor deficiency in immature cumulus-oocyte complexes retrieved for assisted reproduction","authors":"Maíra Casalechi Ph.D.,&nbsp;Maria Thereza V. Pereira M.Sc.,&nbsp;Wiviane A. Assis Ph.D.,&nbsp;Cynthia Dela Cruz Ph.D.,&nbsp;Tays F. Guedes B.Sc.,&nbsp;Ines Katerina Cavallo M.D., Ph.D.,&nbsp;Fernando M. Reis M.D., Ph.D.","doi":"10.1016/j.xfss.2024.12.006","DOIUrl":"10.1016/j.xfss.2024.12.006","url":null,"abstract":"<div><div>This study investigated whether luteinizing hormone receptor (LHR) expression varies in the granulosa cells of individual follicles according to the maturation stage of the oocytes harvested for assisted reproductive technology treatment. We observed minimal to no LHR messenger ribonucleic acid and protein expression in cumulus cells surrounding oocytes arrested in the germinal vesicle stage. Interestingly, their ability to mature was confirmed by rescue in vitro maturation, suggesting somatic cell LHR deficiency as a key factor for the retrieval of germinal vesicle oocytes in assisted reproductive technology procedures.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 126-129"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928795","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}
引用次数: 0
Relugolix reduces leiomyoma extracellular matrix production via the transforming growth factor-beta pathway 乐可利通过 TGF β 途径减少子宫肌瘤细胞外基质的生成。
F&S science Pub Date : 2025-05-01 DOI: 10.1016/j.xfss.2024.12.004
Adina Schwartz M.D. , Minnie Malik Ph.D. , Paul Driggers Ph.D. , William H. Catherino M.D., Ph.D.
{"title":"Relugolix reduces leiomyoma extracellular matrix production via the transforming growth factor-beta pathway","authors":"Adina Schwartz M.D. ,&nbsp;Minnie Malik Ph.D. ,&nbsp;Paul Driggers Ph.D. ,&nbsp;William H. Catherino M.D., Ph.D.","doi":"10.1016/j.xfss.2024.12.004","DOIUrl":"10.1016/j.xfss.2024.12.004","url":null,"abstract":"<div><h3>Objective</h3><div>To determine if the oral gonadotropin-releasing hormone antagonist relugolix affects leiomyoma extracellular matrix production through the transforming growth factor-beta (TGF-β) pathway.</div></div><div><h3>Design</h3><div>Laboratory study.</div></div><div><h3>Subjects</h3><div>None.</div></div><div><h3>Exposure</h3><div>Exposure of human leiomyoma cells to TGF-β and/or relugolix.</div></div><div><h3>Main Outcome Measures</h3><div>Production of TGF-β, pSMAD2/3, SMAD2/3, collagen 1A1 (COL1A1), fibronectin (FN1), and versican (VCAN) in treated and untreated leiomyoma cells.</div></div><div><h3>Results</h3><div>Transforming growth factor-beta 3 production decreased at 24 hours with relugolix 10 nM (0.80 ± 0.09-fold) and 100 nM (0.86 ± 0.06-fold) and at 48 hours with relugolix 1 nM (0.86 ± 0.05-fold) and 100 nM (0.86 ± 0.06-fold). pSMAD2/3 production decreased at 24 hours with relugolix 1 nM (0.71 ± 0.01-fold), 10 nM (0.68 ± 0.01-fold), and 100 nM (0.41 ± 0.10-fold). Compared with relugolix treatment alone at the same concentration, combination treatment at 24 hours resulted in significantly increased COL1A1, FN1, and VCAN production with relugolix 1 nM, 10 nM, and 100 nM. At 48 hours, combination treatment resulted in significantly increased COL1A1, FN1, and VCAN production with relugolix 10 nM and 100 nM.</div></div><div><h3>Conclusion</h3><div>Relugolix regulated leiomyoma size by decreasing COL1A1, FN1, and VCAN production. This effect is at least partly through the TGF-β pathway.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 213-220"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904284","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}
引用次数: 0
Polycystic ovary syndrome and morphokinetic embryonic development: a case-control study evaluating 791 embryos 多囊卵巢综合征与形态动力学胚胎发育:791个胚胎的病例对照研究。
F&S science Pub Date : 2025-05-01 DOI: 10.1016/j.xfss.2025.01.003
Gilad Karavani M.D. , Shira Shapira-Nass M.D. , Natali Schachter-Safrai M.D. , Tal Imbar M.D. , Assaf Ben-Meir M.D.
{"title":"Polycystic ovary syndrome and morphokinetic embryonic development: a case-control study evaluating 791 embryos","authors":"Gilad Karavani M.D. ,&nbsp;Shira Shapira-Nass M.D. ,&nbsp;Natali Schachter-Safrai M.D. ,&nbsp;Tal Imbar M.D. ,&nbsp;Assaf Ben-Meir M.D.","doi":"10.1016/j.xfss.2025.01.003","DOIUrl":"10.1016/j.xfss.2025.01.003","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Design</h3><div>A retrospective case-control study conducted in a university-affiliated in vitro fertilization (IVF) unit.</div></div><div><h3>Subjects</h3><div>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.</div></div><div><h3>Exposure</h3><div>Not applicable.</div></div><div><h3>Main Outcome Measures</h3><div>Embryo development morphokinetic parameters in women with and without PCOS undergoing IVF treatments.</div></div><div><h3>Results</h3><div>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 &gt;75th percentile.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 252-260"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","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}
引用次数: 0
Receptive window might be shorter in patients with endometriosis and lesions cyclically prepare for implantation 子宫内膜异位症患者的接受窗口可能较短,病变周期准备着床。
F&S science Pub Date : 2025-05-01 DOI: 10.1016/j.xfss.2024.11.002
Nirukshi Samarajeewa Ph.D. , Sophea Heng Ph.D. , Ying Li B.Eng. , Maxine Scelwyn M.D. , Luk J. Rombauts M.D. Ph.D. , Guiying Nie Ph.D.
{"title":"Receptive window might be shorter in patients with endometriosis and lesions cyclically prepare for implantation","authors":"Nirukshi Samarajeewa Ph.D. ,&nbsp;Sophea Heng Ph.D. ,&nbsp;Ying Li B.Eng. ,&nbsp;Maxine Scelwyn M.D. ,&nbsp;Luk J. Rombauts M.D. Ph.D. ,&nbsp;Guiying Nie Ph.D.","doi":"10.1016/j.xfss.2024.11.002","DOIUrl":"10.1016/j.xfss.2024.11.002","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate whether endometrial receptivity is affected in patients with endometriosis using podocalyxin (PCX) as a functional biomarker and to study how endometriotic lesions display PCX and the potential pathological implications.</div></div><div><h3>Design</h3><div>We have previously reported that PCX, an anti-adhesion glycoprotein and barrier protector, is dynamically regulated in the endometrium and acts as a key negative regulator of epithelial receptivity. Early in the cycle both luminal epithelium (LE, lining the endometrial surface) and glandular epithelium (GE, residing within the tissue) strongly express PCX, but in the receptive window, PCX is selectively downregulated in LE, switching the endometrial surface to an adhesive state for embryo attachment/implantation; meanwhile, PCX expression is maintained in GE until postreceptivity. Here, we immuno-stained PCX in endometrial tissues and ectopic lesions biopsied across the menstrual cycle from patients with endometriosis (EOS, n = 41), and compared with endometrium of non-endometriosis controls (non-EOS, n = 55). We further investigated how PCX changes observed in ectopic lesions may influence their adhesive capacity.</div></div><div><h3>Subjects</h3><div>Women without and with endometriosis.</div></div><div><h3>Exposure</h3><div>Not applicable.</div></div><div><h3>Main Outcome Measures</h3><div>The window of endometrial receptivity might be shorter in patients with endometriosis; ectopic sites in addition downregulate PCX cyclically, mirroring the eutopic endometrial cells in preparing for receptivity to increase their adhesion potential.</div></div><div><h3>Results</h3><div>Endometrial PCX levels were comparable between non-EOS and EOS early in the cycle, and in both groups, PCX is downregulated in LE during the expected window of receptivity; however, in EOS endometrium, PCX is reduced earlier in GE as if the receptive window were shorter. In endometriotic lesions, PCX was detected in endometrial LE- and GE-like cells plus mesothelial cells enveloping peritoneal organs, but PCX was cyclically lost specifically in LE-like cells and reduced in GE-like cells as seen in the eutopic endometrium, which however may increase their adhesion potential to nearby organs (overlaid by mesothelial cells). This speculation was further corroborated in an in vitro model showing endometrial epithelial cells with lower PCX were indeed more adhesive to mesothelial cells.</div></div><div><h3>Conclusion</h3><div>Endometrial receptivity is subtly affected in patients with endometriosis with a shorter window. Cyclic downregulation of PCX in ectopic sites may have pathological consequences.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 232-241"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792887","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}
引用次数: 0
Chemotherapy-induced diminished murine ovarian reserve model and impact of low-dose chemotherapy on fertility 化疗引起的小鼠卵巢储备功能减退模型及低剂量化疗对生育能力的影响。
F&S science Pub Date : 2025-05-01 DOI: 10.1016/j.xfss.2025.01.002
Lara Houeis M.D. , Graziella van der Plancke B.Sc. , Jen-Yu Wen M.D. , Laurence Dupuy Ph.D. , Elodie Kara Ph.D. , Luciana Cacciottola M.D., Ph.D. , Marie-Christine Maurel Ph.D. , Jacques Donnez M.D., Ph.D. , Marie-Madeleine Dolmans M.D., Ph.D.
{"title":"Chemotherapy-induced diminished murine ovarian reserve model and impact of low-dose chemotherapy on fertility","authors":"Lara Houeis M.D. ,&nbsp;Graziella van der Plancke B.Sc. ,&nbsp;Jen-Yu Wen M.D. ,&nbsp;Laurence Dupuy Ph.D. ,&nbsp;Elodie Kara Ph.D. ,&nbsp;Luciana Cacciottola M.D., Ph.D. ,&nbsp;Marie-Christine Maurel Ph.D. ,&nbsp;Jacques Donnez M.D., Ph.D. ,&nbsp;Marie-Madeleine Dolmans M.D., Ph.D.","doi":"10.1016/j.xfss.2025.01.002","DOIUrl":"10.1016/j.xfss.2025.01.002","url":null,"abstract":"<div><h3>Objective</h3><div>To establish a murine model of chemotherapy-induced diminished ovarian reserve (DOR) and investigate residual fertility after chemotherapy exposure.</div></div><div><h3>Design</h3><div>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.</div></div><div><h3>Subjects</h3><div>Seventy-two Naval Medical Research Institute mice.</div></div><div><h3>Exposure</h3><div>Two different chemotherapy protocols.</div></div><div><h3>Main Outcome Measures</h3><div>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).</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 2","pages":"Pages 177-185"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","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}
引用次数: 0
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