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Environmental factors accelerate epigenetic aging of sperm via mechanistic target of rapamycin/blood-testis barrier mechanism 环境因素通过雷帕霉素/血睾丸屏障机制加速精子表观遗传老化。
F&S science Pub Date : 2026-01-01 Epub Date: 2025-10-10 DOI: 10.1016/j.xfss.2025.10.001
Olatunbosun Arowolo Ph.D. , Oladele A. Oluwayiose Ph.D. , Jiahui Zhu M.D. , Oleg Sergeyev M.D., Ph.D. , Emily Houle M.S. , J Richard Pilsner Ph.D. , Alexander Suvorov Ph.D., Sc.D.
{"title":"Environmental factors accelerate epigenetic aging of sperm via mechanistic target of rapamycin/blood-testis barrier mechanism","authors":"Olatunbosun Arowolo Ph.D. ,&nbsp;Oladele A. Oluwayiose Ph.D. ,&nbsp;Jiahui Zhu M.D. ,&nbsp;Oleg Sergeyev M.D., Ph.D. ,&nbsp;Emily Houle M.S. ,&nbsp;J Richard Pilsner Ph.D. ,&nbsp;Alexander Suvorov Ph.D., Sc.D.","doi":"10.1016/j.xfss.2025.10.001","DOIUrl":"10.1016/j.xfss.2025.10.001","url":null,"abstract":"<div><h3>Objective</h3><div>To identify a common molecular mechanism of sperm epigenome reprograming by environmental factors by testing whether mechanistic target of rapamycin (mTOR)–dependent and mTOR-independent disruption of the blood-testis barrier (BTB) by environmental factors (heat stress [HS] and cadmium [Cd] exposure, respectively) accelerate epigenetic aging of sperm in a mouse model.</div></div><div><h3>Design</h3><div>Using Infinium methylation array, we developed a murine sperm epigenetic clock model and used it to assess epigenetic age shifts in adult mice exposed to environmental factors for the duration of two spermatogenesis cycles.</div></div><div><h3>Subjects</h3><div>C57BL/6 mice.</div></div><div><h3>Exposure</h3><div>Short-term acute intermittent whole-body HS protocol was designed to mimic human HS during heat waves. The Cd exposure group was treated with 1 μL/g body weight of water solution of CdCl<sub>2</sub>.</div></div><div><h3>Main Outcome Measures</h3><div>The activation of mTOR complexes by both stressors was analyzed using enzyme-linked immunosorbent assay. Effects of HS, Cd, and aging on sperm deoxyribonucleic acid methylation were compared using bioinformatic tools.</div></div><div><h3>Results</h3><div>We demonstrate that both mTOR-dependent BTB disruption by HS and mTOR-independent BTB disruption by Cd exposure accelerate sperm epigenetic aging, resulting in similar changes to sperm deoxyribonucleic acid methylation patterns, including changes in methylation of genes involved in embryonic development and neurodevelopment.</div></div><div><h3>Conclusion</h3><div>The mTOR/BTB mechanism is a novel pathway through which environmental and other stressors influence sperm epigenetic aging. This pathway is a potential therapeutic target for the mitigation of environmental effects on epigenetic programs in sperm.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"7 1","pages":"Pages 1-12"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276811","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
Functional stability of the second mitotic spindle in blastomeres and its association with multinucleation repair 卵裂球第二纺锤体的功能稳定性及其与多核修复的关系。
F&S science Pub Date : 2026-01-01 Epub Date: 2025-10-23 DOI: 10.1016/j.xfss.2025.10.003
Taichi Sakaguchi M.D. , Hiromitsu Shirasawa M.D., Ph.D. , Yuki Ono M.D., Ph.D. , Kazumasa Takahashi M.D., Ph.D. , Mayumi Goto A.S. , Motonari Okabe M.D., Ph.D. , Chika Ariake M.D. , Akari Tsuya M.D. , Takeo Hirakawa M.D., Ph.D. , Takuya Iwasawa M.D., Ph.D. , Ayaka Fujishima M.D., Ph.D. , Yohei Onodera M.D., Ph.D. , Tae Sugawara M.D., Ph.D. , Kenichi Makino M.D., Ph.D. , Hiroshi Miura M.D., Ph.D. , Noritaka Fukunaga M.D., Ph.D. , Yoshimasa Asada M.D., Ph.D. , Yukiyo Kumazawa M.D., Ph.D. , Yukihiro Terada M.D., Ph.D.
{"title":"Functional stability of the second mitotic spindle in blastomeres and its association with multinucleation repair","authors":"Taichi Sakaguchi M.D. ,&nbsp;Hiromitsu Shirasawa M.D., Ph.D. ,&nbsp;Yuki Ono M.D., Ph.D. ,&nbsp;Kazumasa Takahashi M.D., Ph.D. ,&nbsp;Mayumi Goto A.S. ,&nbsp;Motonari Okabe M.D., Ph.D. ,&nbsp;Chika Ariake M.D. ,&nbsp;Akari Tsuya M.D. ,&nbsp;Takeo Hirakawa M.D., Ph.D. ,&nbsp;Takuya Iwasawa M.D., Ph.D. ,&nbsp;Ayaka Fujishima M.D., Ph.D. ,&nbsp;Yohei Onodera M.D., Ph.D. ,&nbsp;Tae Sugawara M.D., Ph.D. ,&nbsp;Kenichi Makino M.D., Ph.D. ,&nbsp;Hiroshi Miura M.D., Ph.D. ,&nbsp;Noritaka Fukunaga M.D., Ph.D. ,&nbsp;Yoshimasa Asada M.D., Ph.D. ,&nbsp;Yukiyo Kumazawa M.D., Ph.D. ,&nbsp;Yukihiro Terada M.D., Ph.D.","doi":"10.1016/j.xfss.2025.10.003","DOIUrl":"10.1016/j.xfss.2025.10.003","url":null,"abstract":"<div><h3>Objective</h3><div>To study mitotic spindle morphology and chromosomal segregation in second mitosis.</div></div><div><h3>Design</h3><div>Live-cell imaging of deoxyribonucleic acid (DNA) and tubulin during the second mitosis of 21 freeze-thawed human two-pronuclear stage embryos was performed to analyze spindle morphology and chromosome segregation dynamics. Furthermore, chromosomal aneuploidy was assessed in all cells of the embryos that developed to the blastocyst stage.</div></div><div><h3>Subjects</h3><div>Twenty-one freeze-thawed human two-pronuclear embryos.</div></div><div><h3>Exposure</h3><div>We analyzed live-imaging videos of DNA and microtubules during the second division of 21 human 2-cell embryonic blastomeres. We further analyzed the association between the results of preimplantation genetic testing for aneuploidy of all cells in the observed embryos after development into blastocysts and the nuclear status at the early embryonic stage.</div></div><div><h3>Main Outcome Measures</h3><div>Spindle morphology during the second mitosis, chromosomal segregation patterns, nuclear status of daughter blastomeres, and chromosomal aneuploidy of all cells in blastocysts derived from the observed embryos.</div></div><div><h3>Results</h3><div>Multinucleation rate in daughter nuclei was significantly lower after the second than after the first mitosis (22% vs. 56%). Neither defocusing of spindle poles—which was prominent in the first mitosis—nor chromosomal segregation abnormalities, such as misalignment of metaphase chromosomes and lagging chromosomes during chromosomal segregation, were observed. There was no association between the nuclear status at the 2- and 4-cell stages of the observed embryos that had progressed to the blastocyst stage and the preimplantation genetic testing for aneuploidy results of all cells in the blastocysts.</div></div><div><h3>Conclusion</h3><div>Observations of mitotic spindle morphology and chromosomal segregation behavior revealed that second mitosis is less prone to chromosomal segregation errors than first mitosis. This suggests that segregation errors occurring during the first mitosis may be corrected during the second mitosis. Furthermore, there was no association between the nuclear status during early embryonic divisions and the chromosomal status of blastocyst cells, suggesting the presence of a mechanism that corrects chromosomal abnormalities during early development.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"7 1","pages":"Pages 61-73"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370466","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
Lactobacillus reuteri protects against heat stress-induced testicular dysfunction by modulating oxidative stress and autophagy pathways in rats 罗伊氏乳杆菌通过调节氧化应激和自噬途径防止大鼠热应激诱导的睾丸功能障碍
F&S science Pub Date : 2026-01-01 Epub Date: 2025-10-24 DOI: 10.1016/j.xfss.2025.10.004
Samira Parsaeinejad M.Sc. , Vahid Nejati Ph.D. , Mazdak Razi Ph.D. , Amir Tokmechi Ph.D.
{"title":"Lactobacillus reuteri protects against heat stress-induced testicular dysfunction by modulating oxidative stress and autophagy pathways in rats","authors":"Samira Parsaeinejad M.Sc. ,&nbsp;Vahid Nejati Ph.D. ,&nbsp;Mazdak Razi Ph.D. ,&nbsp;Amir Tokmechi Ph.D.","doi":"10.1016/j.xfss.2025.10.004","DOIUrl":"10.1016/j.xfss.2025.10.004","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the potential of <em>Lactobacillus reuteri</em> (Lr) in ameliorating heat stress (HS)–induced testicular damage through modulation of oxidative stress and autophagy.</div></div><div><h3>Design</h3><div>Experimental controlled study involving adult male Wistar rats exposed to HS and/or probiotic treatment.</div></div><div><h3>Subjects</h3><div>Adult male Wistar rats divided into six groups: control, Lr-only (LrP-sole), HS-only (37 °C and 40 °C), and Lr-treated HS groups.</div></div><div><h3>Intervention</h3><div>Heat stress was induced by immersing the scrotal area in a water bath at 37 °C or 40 °C for 20 minutes daily over 42 days. <em>Lactobacillus reuteri</em> probiotic (5 × 10<sup>8</sup> CFU/mL) was administered orally throughout the experimental period.</div></div><div><h3>Main Outcome Measures</h3><div>Sperm count, motility, viability, nuclear maturity, and deoxyribonucleic acid integrity; testicular histopathology; total antioxidant capacity and total oxidant status; expression of autophagy-related genes (p62, Atg7, Beclin-1, and LC3-I) by quantitative reverse transcriptase polymerase chain reaction; and LC3-I/II protein levels by immunohistochemistry.</div></div><div><h3>Results</h3><div>Heat stress significantly impaired spermatogenesis, spermiogenesis, and sperm quality, with elevated oxidative and autophagic stress, particularly at 40 °C. <em>L. reuteri</em> probiotic treatment significantly improved sperm parameters, restored spermatogenic activity, reduced total oxidant status, and enhanced antioxidant capacity. Moreover, Lr modulated the expression of p62, Atg7, Beclin-1, and LC3-I/II, indicating regulation of autophagic pathways and mitigation of oxidative stress within the testicular microenvironment.</div></div><div><h3>Conclusion</h3><div><em>Lactobacillus reuteri</em> confers robust protection against HS-induced testicular dysfunction, likely through modulation of oxidative stress and autophagy. These findings highlight the therapeutic potential of probiotics as a noninvasive intervention to counteract heat-induced male infertility.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"7 1","pages":"Pages 35-48"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915423","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
Dose-dependent modulation of luteinizing hormone receptor expression in human granulosa cells and progesterone production during ovarian stimulation 卵巢刺激过程中人颗粒细胞LH受体表达和黄体酮产生的剂量依赖性调节。
F&S science Pub Date : 2026-01-01 Epub Date: 2025-11-20 DOI: 10.1016/j.xfss.2025.11.002
Barbara Lawrenz Ph.D. , Sahar Ghafari D.V.M. , Erkan Kalafat Ph.D. , Araz Raberi Ph.D. , Jonalyn Edades M.Sc. , Bhanu Kalra Ph.D. , Noreen Hourani M.Sc. , Virginia Ferracuti M.Sc. , Asina Bayram M.Sc. , Human Fatemi Ph.D.
{"title":"Dose-dependent modulation of luteinizing hormone receptor expression in human granulosa cells and progesterone production during ovarian stimulation","authors":"Barbara Lawrenz Ph.D. ,&nbsp;Sahar Ghafari D.V.M. ,&nbsp;Erkan Kalafat Ph.D. ,&nbsp;Araz Raberi Ph.D. ,&nbsp;Jonalyn Edades M.Sc. ,&nbsp;Bhanu Kalra Ph.D. ,&nbsp;Noreen Hourani M.Sc. ,&nbsp;Virginia Ferracuti M.Sc. ,&nbsp;Asina Bayram M.Sc. ,&nbsp;Human Fatemi Ph.D.","doi":"10.1016/j.xfss.2025.11.002","DOIUrl":"10.1016/j.xfss.2025.11.002","url":null,"abstract":"<div><h3>Objective</h3><div>To assess the impact of different recombinant follicle-stimulating hormone (recFSH) dosages in ovarian stimulation (OS) on luteinizing hormone (LH)–receptor and FSH-receptor expression in granulosa cells (GCs) and progesterone level.</div></div><div><h3>Design</h3><div>Prospective interventional study (07/2023–02/2024).</div></div><div><h3>Subjects</h3><div>Six volunteers with regular cycles and normal ovarian reserve undergoing two OS cycles for oocyte vitrification as a means of elective fertility preservation.</div></div><div><h3>Exposure</h3><div>Different recFSH dosages (150 IU vs. 300 IU) in two OS cycles, performed in a gonadotropin-releasing hormone–antagonist protocol.</div></div><div><h3>Main Outcome Measures</h3><div>The LH receptor expression on GCs.</div></div><div><h3>Results</h3><div>Volunteers had a median age of 34 years (range: 28–36), a median antimüllerian hormone–level of 2.28 ng/mL (interquartile range [IQR]: 2.41–3.35) and a median antral follicle count of 13.5 (IQR:12–14) in the 150 IU and 13 (12–15) in the 300 IU OS cycle. Median total recFSH dosages were 1650 IU (IQR: 1350–1800IU)/3150 IU (IQR: 3000–3300) in the 150 IU/300 IU OS cycle, respectively. The number of retrieved cumulus-oocyte-complexes was (median and IQR) 11.5 (10–14)/12.5 (7–15), the number of mature oocytes (median and IQR) of 10.5 (7–12)/10 (6–12), respectively, without a statistically significant difference.</div><div>Besides the stimulation start, serum FSH levels of the 300 IU-cycle were significantly higher compared with the 150 IU-cycle. Estradiol levels were significantly higher in the 300 IU-group on day 5 and at follicle size of 14–16 mm. Progesterone (P4) levels were not statistically significantly different between the stimulation cycles.</div><div>The LH receptor expression in the GCs at oocyte-pick up was significantly higher and FSH-receptor expression was significantly lower in the 300 IU-group compared with the 150 IU-group. The P4 levels on oocyte-pick up day were significantly associated with LH receptor levels after adjusting for the recFSH dose. Furthermore, a significant and independent association of the recFSH dose between the P4 levels and the LH receptor levels was seen on the day of oocyte retrieval.</div></div><div><h3>Conclusion</h3><div>Higher recFSH dosages during OS are associated with increased LH receptor expression, and LH receptor count had a significant association with serum P4 levels.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"7 1","pages":"Pages 27-34"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582800","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
Complementary therapeutic actions of Shikonin and Indole propionic acid ameliorate diabetic infertility via distinct antioxidant and metabolic pathways 紫草素和吲哚丙酸通过不同的抗氧化和代谢途径改善糖尿病不孕症的互补治疗作用。
F&S science Pub Date : 2026-01-01 Epub Date: 2025-11-17 DOI: 10.1016/j.xfss.2025.11.001
Imran Tarique Ph.D., Ali Haider M.S., Fatima Nawazish M.S.
{"title":"Complementary therapeutic actions of Shikonin and Indole propionic acid ameliorate diabetic infertility via distinct antioxidant and metabolic pathways","authors":"Imran Tarique Ph.D.,&nbsp;Ali Haider M.S.,&nbsp;Fatima Nawazish M.S.","doi":"10.1016/j.xfss.2025.11.001","DOIUrl":"10.1016/j.xfss.2025.11.001","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the effect of Shikonin, a potent direct reactive oxygen species (ROS) scavenger, and Indole propionic acid (IPA), a microbiome-derived metabolite, on epididymis and sperm morphology and function in diabetic rats.</div></div><div><h3>Design</h3><div>A rat model of Type 2 diabetes mellitus (T2DM) was induced in male Wistar rats using a high-fat diet and streptozotocin (50 mg/kg). The animals were subsequently divided into seven groups: Control, T2DM, T2DM + IPA (50 mg/kg), T2DM + Shikonin (0.5 mg/kg), T2DM + Metformin (50 mg/kg), IPA-only, and Shikonin-only. Treatments were administered orally for 4 weeks. We assessed histological integrity, sperm motility, and viability (via computer-assisted sperm analysis), serum lipid profiles, epididymal antioxidant activity (superoxide dismutase, malondialdehyde, and catalase), and apoptotic marker (cytochrome C, caspase-9, and caspase-3) and metabolic signature (fibroblast growth factor 21 [FGF21]) expression via quantitative reverse transcription polymerase chain reaction.</div></div><div><h3>Subjects</h3><div>Male Wistar albino rats (n = 42, Age: 8–12 weeks old, 200 ± 2.4 g).</div></div><div><h3>Intervention</h3><div>Streptozotocin, Shikonin, Indole propionic acid.</div></div><div><h3>Main Outcome Measures</h3><div>Type 2 diabetes mellitus profoundly impairs male fertility, with oxidative stress in the epididymis being a key driver of sperm damage.</div></div><div><h3>Results</h3><div>Streptozotocin-induced diabetic rats exhibited increased oxidative damage, characterized by an impaired antioxidant system, high expression of apoptotic markers, and reduced metabolic gene expression. These effects ultimately damaged epididymis tissue and resulted in poor sperm quality. Shikonin and IPA treatments significantly attenuated oxidative stress and apoptosis, restored antioxidant activity and lipid profiles, and improved sperm parameters. Both treatments enhanced metabolic balance, as indicated by improved FGF21 expression, and restored epididymal histoarchitecture. Shikonin was superior in improving the epididymal somatic index and sperm motility, whereas IPA was more effective in normalizing FGF21 expression and lipid profiles, highlighting its primary metabolic role.</div></div><div><h3>Conclusion</h3><div>Our findings reveal that Shikonin and IPA protect against diabetic reproductive damage through complementary pathways. This work not only introduces promising natural therapeutic strategies but also provides a mechanistic framework for their combined or targeted use in managing diabetic infertility.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"7 1","pages":"Pages 100-112"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145558288","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
Deciphering estrogen receptor alpha–driven transcription in human endometrial stromal cells via transcriptome, cistrome, and integration with chromatin landscape 通过转录组、池质和染色质景观整合,解读人类子宫内膜基质细胞中esr1驱动的转录。
F&S science Pub Date : 2026-01-01 Epub Date: 2025-08-11 DOI: 10.1016/j.xfss.2025.08.002
Skylar G. Montague Redecke B.Sc. , Austin Bell-Hensley Ph.D. , Shuyun Li Ph.D. , MyeongJin Yi Ph.D. , Akshadha Jain , Abdull J. Massri Ph.D. , Francesco J. DeMayo Ph.D.
{"title":"Deciphering estrogen receptor alpha–driven transcription in human endometrial stromal cells via transcriptome, cistrome, and integration with chromatin landscape","authors":"Skylar G. Montague Redecke B.Sc. ,&nbsp;Austin Bell-Hensley Ph.D. ,&nbsp;Shuyun Li Ph.D. ,&nbsp;MyeongJin Yi Ph.D. ,&nbsp;Akshadha Jain ,&nbsp;Abdull J. Massri Ph.D. ,&nbsp;Francesco J. DeMayo Ph.D.","doi":"10.1016/j.xfss.2025.08.002","DOIUrl":"10.1016/j.xfss.2025.08.002","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate estrogen receptor gene 1 (ESR1) and estrogen-driven transcription in human endometrial stromal cells.</div></div><div><h3>Design</h3><div>RNA sequencing (RNA-seq) and Cleavage Under Targets and Release Using Nuclease (Cut&amp;Run) were performed on telomerase-immortalized human endometrial stromal cells with Clustered Regularly Interspaced Short Palindromic Repeats–mediated ESR1 activation. Hi-C-based chromatin architecture analysis (H3K27ac HiChIP) was conducted in primary endometrial stromal cells.</div></div><div><h3>Subjects</h3><div>Biopsies from two healthy, reproductive-aged volunteers with regular menstrual cycles and no history of gynecological malignancies.</div></div><div><h3>Exposure</h3><div>The ESR1-activated and control endometrial stromal cells were treated with estradiol (E2) or vehicle. Primary endometrial stromal cells were treated with vehicle or a decidualization cocktail.</div></div><div><h3>Main Outcome Measures</h3><div>Differential gene expression analysis (RNA-seq) identified ligand-independent and -dependent ESR1 activity. Cut&amp;Run profiled ESR1 genomic binding in ESR1-activated cells. H3K27ac HiChIP mapped hormone-induced changes in chromatin looping in primary cells.</div></div><div><h3>Results</h3><div>Among seven tested guide RNAs (gRNA), the ESR1-3 gRNA induced robust ESR1 activation and restored E2 responsiveness. Bulk RNA-seq revealed both ligand-dependent and -independent ESR1 transcriptional programs regulating inflammation, proliferation, and cancer-related pathways. Notably, 72% of differentially expressed genes overlapped with genes active in human endometrial tissue during the proliferative estrogen-dominant phase, supporting their physiological relevance. The Cut&amp;Run-seq identified genome-wide ESR1 binding sites, with most binding sites located at distal regulatory elements. Integration of Cut&amp;Run data with H3K27ac HiChIP chromatin loops linked distal ESR1 binding sites to gene promoters, including genes involved in decidualization (e.g., <em>FOXO1</em>) and endometrial cancer (e.g., <em>ERRFI1</em>, <em>NRIP1</em>, and <em>EPAS1</em>). Functional assays showed that ESR1 promotes cell viability and, in the presence of E2, enhances migration.</div></div><div><h3>Conclusion</h3><div>The CRISPR-mediated ESR1 activation restores estrogen responsiveness in endometrial stromal cells. Combined transcriptomic, cistromic, and chromatin architecture analyses reveal ESR1’s role in regulating decidualization and inflammation-related gene networks, with relevance to endometrial pathologies including endometrial cancer. This model serves as a powerful tool to study estrogen signaling in endometrial stromal cell biology and related pathologies.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"7 1","pages":"Pages 74-90"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849965","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
Euploid but failing to implant? Insights from trophectoderm transcriptomics of euploid blastocysts using an in vitro model 整倍体但未能植入?利用体外模型观察整倍体囊胚的滋养外胚层转录组学。
F&S science Pub Date : 2026-01-01 Epub Date: 2025-10-13 DOI: 10.1016/j.xfss.2025.09.003
David Ortega-Jaén M.Sc. , Antonio Capalbo Ph.D. , Ángel Martín Ph.D. , Julia Gil M.Sc. , María Luisa Pardiñas M.Sc. , Carlos Mora-Martinez Ph.D. , Mireia Boluda-Navarro Ph.D. , Amparo Mercader Ph.D. , María José de los Santos Ph.D.
{"title":"Euploid but failing to implant? Insights from trophectoderm transcriptomics of euploid blastocysts using an in vitro model","authors":"David Ortega-Jaén M.Sc. ,&nbsp;Antonio Capalbo Ph.D. ,&nbsp;Ángel Martín Ph.D. ,&nbsp;Julia Gil M.Sc. ,&nbsp;María Luisa Pardiñas M.Sc. ,&nbsp;Carlos Mora-Martinez Ph.D. ,&nbsp;Mireia Boluda-Navarro Ph.D. ,&nbsp;Amparo Mercader Ph.D. ,&nbsp;María José de los Santos Ph.D.","doi":"10.1016/j.xfss.2025.09.003","DOIUrl":"10.1016/j.xfss.2025.09.003","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate transcriptomic differences in mural trophectoderm (TE) cells of euploid human blastocysts on the basis of their ability to remain attached in extended in vitro culture and to identify gene expression profiles associated with competence for implantation.</div></div><div><h3>Design</h3><div>Prospective in vitro experimental cohort study involving ribonucleic acid sequencing of mural TE biopsies from euploid blastocysts and extended culture up to day 11.</div></div><div><h3>Subjects</h3><div>Fifteen euploid blastocysts donated by 16 couples undergoing intracytoplasmic sperm injection and preimplantation genetic testing for aneuploidy. Transcriptomic comparison focused on 10 euploid blastocysts, classified as attached (n = 5) or unattached (n = 5) after extended in vitro culture, and the rest were excluded for various reasons.</div></div><div><h3>Exposure</h3><div>Development outcome of euploid blastocysts during extended in vitro culture (adhesion vs. non-adhesion to the culture surface on day 11), used as the basis for differential gene expression analysis.</div></div><div><h3>Main Outcome Measures</h3><div>Identification of differentially expressed genes and deregulated molecular pathways between attached and unattached euploid embryos, including functional enrichment analysis to explore their potential roles in embryo viability and implantation.</div></div><div><h3>Results</h3><div>Transcriptomic analysis revealed 85 differentially expressed genes between unattached and attached euploid blastocysts, including genes involved in cellular adhesion (e.g., <em>SPON2</em> and <em>VTN</em>), immune modulation (<em>HLA-G</em> and <em>IL12A</em>), metabolism (<em>NNMT</em> and <em>CYP3A7</em>), and mitochondrial function. Unattached embryos displayed down-regulation of ribosome biogenesis, mitochondrial proteins, and chromosomal segregation pathways and up-regulation of genes related to immune response and cytoskeletal organization.</div></div><div><h3>Conclusion</h3><div>The study demonstrates that mural TE gene expression differs significantly between euploid blastocysts that attach and those that do not, highlighting molecular pathways potentially linked to implantation success. Despite human implantation typically occurring through the polar TE, mural TE transcriptomic profiles may provide predictive value for embryo selection and deepen our understanding of early implantation biology. Further validation through proteomic studies and larger cohorts is needed to confirm these candidate biomarkers.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"7 1","pages":"Pages 49-60"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145304784","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
Transvaginal shear wave elastography for measuring uterine myometrial and leiomyoma stiffness: a protocol pilot study 经阴道横波弹性成像测量子宫肌瘤和平滑肌瘤硬度:一项方案试点研究。
F&S science Pub Date : 2026-01-01 Epub Date: 2025-09-09 DOI: 10.1016/j.xfss.2025.09.002
Hannah T. Ryles M.D. , Sumeyra Agambayev M.S. , Mervat Omran Ph.D. , Chuanhong Liao M.S. , Samar Alkhrait M.D. , Ayman Al-Hendy M.D. , Ryan Longman M.D. , Jacques Abramowicz M.D. , Obianuju Sandra Madueke-Laveaux M.D.
{"title":"Transvaginal shear wave elastography for measuring uterine myometrial and leiomyoma stiffness: a protocol pilot study","authors":"Hannah T. Ryles M.D. ,&nbsp;Sumeyra Agambayev M.S. ,&nbsp;Mervat Omran Ph.D. ,&nbsp;Chuanhong Liao M.S. ,&nbsp;Samar Alkhrait M.D. ,&nbsp;Ayman Al-Hendy M.D. ,&nbsp;Ryan Longman M.D. ,&nbsp;Jacques Abramowicz M.D. ,&nbsp;Obianuju Sandra Madueke-Laveaux M.D.","doi":"10.1016/j.xfss.2025.09.002","DOIUrl":"10.1016/j.xfss.2025.09.002","url":null,"abstract":"<div><h3>Objective</h3><div>Recent studies suggest that the stiffness of uterine leiomyomas may be related to their growth and behavior. Shear wave elastography (SWE), a quantitative method of measuring tissue stiffness, has been increasingly studied for use in gynecologic conditions. However, no protocols have been proposed for its use in this clinical setting. This study aimed to establish a standardized protocol for transvaginal SWE to measure uterine myometrial and leiomyoma stiffness and assess the reproducibility and reliability of SWE measurements. We also assessed myometrial vs. leiomyoma stiffness, compared myometrial stiffness in participants with and without leiomyomas, and assessed menstrual phase effects on stiffness values.</div></div><div><h3>Design</h3><div>Transvaginal SWE ultrasound measurements of myometrial and leiomyoma stiffness were obtained. All transvaginal SWE examinations were performed by an individual sonographer. Independent raters calculated stiffness measurements. Myometrial and leiomyoma stiffness were compared across menstrual phases.</div></div><div><h3>Subjects</h3><div>Twenty-seven premenopausal women, 16 with leiomyomas and 11 without, were enrolled. Seventeen participants completed examinations during multiple menstrual phases.</div></div><div><h3>Exposure</h3><div>Tissue type (myometrium/leiomyoma), leiomyoma status (presence/absence of leiomyomas), and menstrual phase (follicular/luteal).</div></div><div><h3>Main Outcome Measures</h3><div>Interrater and test-retest reliability of SWE measurements. Myometrial and leiomyoma shear wave values.</div></div><div><h3>Results</h3><div>We successfully designed a streamlined protocol for obtaining SWE measurements in participants with and without leiomyomas. Fifty-one myometrial and 38 leiomyoma stiffness values measured by 2 independent raters achieved excellent interrater reliability: the intraclass correlation coefficients between the 2 raters were 0.990 and 0.994, respectively. Fifty myometrial and 42 leiomyoma stiffness measurements calculated by a single rater at 2 time points at least 90 days apart achieved excellent test-retest reliability: intraclass correlation coefficients of 0.992 and 0.995. The median stiffness values for leiomyomas were significantly higher than those for the surrounding myometrium (48.1 [interquartile range, 39.7–59.5] vs. 31.6 [interquartile range, 22.9–46.9] kPa). There was no significant change in myometrial or leiomyoma median stiffness values between the menstrual phases.</div></div><div><h3>Conclusion</h3><div>Transvaginal ultrasound SWE showed excellent reproducibility and reliability in measuring myometrial and leiomyoma stiffness. Leiomyoma stiffness was significantly higher than that for the surrounding myometrium. Together, these findings support SWE’s potential clinical utility in leiomyoma management.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"7 1","pages":"Pages 91-99"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042452","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
Enhanced sperm cryopreservation using zinc- and copper-doped hydroxyapatite with glutathione and raffinose: effects on motility, viability, deoxyribonucleic acid integrity, and oxidative stress markers 添加谷胱甘肽和棉子糖的锌和铜掺杂羟基磷灰石增强精子低温保存:对精子活力、活力、脱氧核糖核酸完整性和氧化应激标志物的影响
F&S science Pub Date : 2026-01-01 Epub Date: 2025-10-25 DOI: 10.1016/j.xfss.2025.10.005
Asma Mahmoudi D.V.M. , Mazdak Razi Ph.D. , Marzieh Jalilpour Ph.D. , Ali Shalizar Jalali Ph.D.
{"title":"Enhanced sperm cryopreservation using zinc- and copper-doped hydroxyapatite with glutathione and raffinose: effects on motility, viability, deoxyribonucleic acid integrity, and oxidative stress markers","authors":"Asma Mahmoudi D.V.M. ,&nbsp;Mazdak Razi Ph.D. ,&nbsp;Marzieh Jalilpour Ph.D. ,&nbsp;Ali Shalizar Jalali Ph.D.","doi":"10.1016/j.xfss.2025.10.005","DOIUrl":"10.1016/j.xfss.2025.10.005","url":null,"abstract":"<div><h3>Objective</h3><div>To study the protective effects of zinc- and copper-doped hydroxyapatite (H) combined with glutathione (GSH) and raffinose (R) on mouse sperm motility, viability, deoxyribonucleic acid (DNA) integrity, and oxidative stress markers before and after cryopreservation.</div></div><div><h3>Design</h3><div>Experimental laboratory-controlled study evaluating the efficacy of combined cryoprotective formulations during sperm cryopreservation.</div></div><div><h3>Subjects</h3><div>Sperm samples collected from 10 healthy adult albino mice were used for in vitro cryopreservation experiments.</div></div><div><h3>Intervention</h3><div>Samples were divided into six groups: a control group using a commercial cryopreservation medium and five experimental groups supplemented with H, GSH, and R, either alone or in combination (H+GSH+R). All samples were cryopreserved at −196°C for 72 hours and subsequently thawed for analysis.</div></div><div><h3>Main Outcome Measures</h3><div>Postthaw sperm motility, viability, and DNA fragmentation were evaluated, along with biochemical markers of oxidative stress, including total antioxidant capacity, total oxidant status, lipid peroxidation, protein oxidation, and enzymatic activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase.</div></div><div><h3>Results</h3><div>The H+GSH+R group demonstrated significantly higher motility and lower DNA fragmentation and mortality compared with the control. Total antioxidant capacity increased prefreezing, although total oxidant status was markedly reduced postthaw. Lipid and protein oxidation decreased significantly, and antioxidant enzyme activities were enhanced in the H+GSH+R group.</div></div><div><h3>Conclusion</h3><div>Zinc- and copper-doped H combined with GSH and R effectively improves sperm cryosurvival by enhancing antioxidant defenses and reducing oxidative damage. This formulation provides a promising cryoprotective strategy for optimizing assisted reproductive technologies.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"7 1","pages":"Pages 13-26"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145915422","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
Laparoscopic ovarian drilling vs. step-up gonadotropin therapy in infertile anovulatory polycystic ovary syndrome women resistant to sequential letrozole and gonadotropin-based ovulation induction cycles: a randomized controlled trial 腹腔镜卵巢钻孔(LOD)与促性腺激素强化治疗对序贯来曲唑和促性腺激素促排卵周期有抗性的不育性无排卵性多囊卵巢综合征(PCOS):一项随机对照试验。
F&S science Pub Date : 2025-11-01 Epub Date: 2025-08-05 DOI: 10.1016/j.xfss.2025.07.006
H.V. Bhavana M.D. , Reeta Mahey M.D., D.N.B. , Aarthi K. Jayraj M.D., D.N.B. , Ashish Datt Upadhyay Ph.D. , Archana Kumari M.D. , Garima Kachhawa M.D. , Ayushi Negi M.D. , Khushbu Bashir M.D. , Srikar Yedlapalli M.S.
{"title":"Laparoscopic ovarian drilling vs. step-up gonadotropin therapy in infertile anovulatory polycystic ovary syndrome women resistant to sequential letrozole and gonadotropin-based ovulation induction cycles: a randomized controlled trial","authors":"H.V. Bhavana M.D. ,&nbsp;Reeta Mahey M.D., D.N.B. ,&nbsp;Aarthi K. Jayraj M.D., D.N.B. ,&nbsp;Ashish Datt Upadhyay Ph.D. ,&nbsp;Archana Kumari M.D. ,&nbsp;Garima Kachhawa M.D. ,&nbsp;Ayushi Negi M.D. ,&nbsp;Khushbu Bashir M.D. ,&nbsp;Srikar Yedlapalli M.S.","doi":"10.1016/j.xfss.2025.07.006","DOIUrl":"10.1016/j.xfss.2025.07.006","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To study the effect of laparoscopic ovarian drilling (LOD) vs. step-up gonadotropin therapy on follicular response in infertile anovulatory polycystic ovary syndrome (PCOS) women resistant to sequential letrozole + human menopausal gonadotropin (HMG)–based ovulation induction (OVI) cycles.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design&lt;/h3&gt;&lt;div&gt;Open-labeled, pilot, randomized controlled trial.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Subjects&lt;/h3&gt;&lt;div&gt;Infertile anovulatory PCOS women (diagnosed according to modified Rotterdam criteria), resistant to sequential letrozole 5 mg + HMG-based OVI cycle (no dominant follicle &gt;10 mm after 14 days of stimulation). Other inclusion criteria were: age 19–38 years; body mass index ≤35 kg/m&lt;sup&gt;2&lt;/sup&gt;; patent fallopian tubes documented on either hysterosalpingography/saline infusion sonography or laparoscopy; antimüllerian hormone (AMH) levels &gt;6 ng/mL. Exclusion criteria were AMH ≤6 ng/mL; moderate to severe male factor infertility and endometriosis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Intervention&lt;/h3&gt;&lt;div&gt;Participants in group 1 (N = 35) underwent LOD, after which OVI cycles were started with letrozole 5 mg from the following menses. Gonadotropin were added in a sequential manner if required as per the follicular response. Women in group 2 (N = 35) were administered injection of HMG (75 IU) from day 2 of menses and dose increments were done from day 9 onward as per response.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main Outcome Measures&lt;/h3&gt;&lt;div&gt;Primary outcome was follicular response (dominant follicle &gt;16 mm). Secondary objectives were gonadotropin requirement per cycle, duration of stimulation, time to conception (months), clinical pregnancy rate and ongoing pregnancy rate (&gt;12 weeks). The study also compared the effect of LOD on hormonal parameters (AMH, serum testosterone) and metabolic parameters (fasting insulin, fasting blood glucose, lipid profile, homeostasis model assessment of insulin resistance) after 1–2 months of procedure.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Majority of the study participants (82.85%) belonged to PCOS phenotype A. The baseline clinical, hormonal, and metabolic characteristics and phenotype distribution were comparable in both groups. The follicular response was significantly higher in the LOD group (93.25%; 83/89) compared with step-up gonadotropin group (28.20%; 11/39). With four spontaneous conceptions, the median time to conception in LOD group was 3.9 (0–8.4) months. The clinical pregnancy rate per patient was significantly higher in LOD group [54.28% (19/35)] as compared with step-up gonadotropin group [8.57% (3/35)]. The ongoing pregnancy rate in the LOD group was 45.71% (16/35) vs. 0% (0/35) in the gonadotropin group. There was a significant fall in the AMH levels from 15.2 ± 2.7 ng/mL to 10.2 ± 4.4 ng/mL after LOD. Although statistically insignificant, the levels of luteinizing hormone/follicle-stimulating hormone ratio, testosterone, fasting insulin, fasting glucose and homeostasis model assessment of","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 4","pages":"Pages 453-462"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786088","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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