Chen Zhang, Hongyan Cheng, Sha Dou, Yuanfen Wang, Xue Ye, Heng Cui, Xiaohong Chang, Yi Li
{"title":"Near-infrared fluorescent molecular probes with cetuximab in the in vivo fluorescence imaging for epithelial ovarian cancer.","authors":"Chen Zhang, Hongyan Cheng, Sha Dou, Yuanfen Wang, Xue Ye, Heng Cui, Xiaohong Chang, Yi Li","doi":"10.1186/s13048-024-01547-5","DOIUrl":"10.1186/s13048-024-01547-5","url":null,"abstract":"<p><strong>Background: </strong>Near-infrared fluorescence (NIRF) imaging is an excellent choice for image-guided surgery due to its simple operation and non-invasiveness. Developing tumor-specific fluorescent molecular probes is key to fluorescence imaging-guided surgery. EGFR (epidermal growth factor receptor) is closely related to the proliferation and growth of tumor cells and is highly expressed in epithelial ovarian cancer (EOC). The study aims to construct a NIR fluorescent molecular probe using cetuximab (an EGFR monoclonal antibody) and investigate its feasibility for targeting EOC in vivo through fluorescence imaging.</p><p><strong>Methods: </strong>We determined the expression of EGFR in EOC. NIR fluorescent molecular probe with cetuximab (cetuximab-Cy7) was chemically engineered and identified. The subcutaneous xenografted tumor model of EOC was induced using SKOV3-Luc cell line with positive expression of EGFR. Cetuximab-Cy7 was used for in vivo fluorescence imaging, and phosphate-buffered saline, free Cy7 dye and mouse isotype immunoglobulin G-Cy7 were used as controls. NIRF imaging system was performed to study the distribution and targeting of the probes. Tumors were imaged in situ and ex vivo, and fluorescent intensity was quantified. Resected specimens were analyzed to confirm diagnosis, and immunohistochemical (IHC) staining was used to identify EGFR expression.</p><p><strong>Results: </strong>EGFR expression was increased in EOC tissues than fallopian tube tissues. The high expression of EGFR was significantly correlated with well-differentiation, residual lesions ≤ 1 cm, no recurrence and increased survival. NIRF imaging showed that the cetuximab-Cy7 enabled detection of tumor lesions in EOC-bearing mice with the optimal dose of 30 µg. The suitable imaging time window may be 24-96 h post-injection. Ex vivo fluorescence imaging indicated that fluorescent signal was mainly detected in the tumor and the lung. IHC results confirmed that xenografts were EGFR positive.</p><p><strong>Conclusion: </strong>Cetuximab-Cy7 can specifically target the tumors of EOC xenografted nude mice. This research lays the foundation for future studies on EOC surgery navigation.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"225"},"PeriodicalIF":3.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mary P Udumula, Faraz Rashid, Harshit Singh, Tim Pardee, Sanjeev Luther, Tanya Bhardwaj, Km Anjaly, Sofia Piloni, Miriana Hijaz, Radhika Gogoi, Philip A Philip, Adnan R Munkarah, Shailendra Giri, Ramandeep Rattan
{"title":"Targeting mitochondrial metabolism with CPI-613 in chemoresistant ovarian tumors.","authors":"Mary P Udumula, Faraz Rashid, Harshit Singh, Tim Pardee, Sanjeev Luther, Tanya Bhardwaj, Km Anjaly, Sofia Piloni, Miriana Hijaz, Radhika Gogoi, Philip A Philip, Adnan R Munkarah, Shailendra Giri, Ramandeep Rattan","doi":"10.1186/s13048-024-01546-6","DOIUrl":"10.1186/s13048-024-01546-6","url":null,"abstract":"<p><strong>Background: </strong>There is evidence indicating that chemoresistance in tumor cells is mediated by the reconfiguration of the tricarboxylic acid cycle, leading to heightened mitochondrial activity and oxidative phosphorylation (OXPHOS). Previously, we have shown that ovarian cancer cells that are resistant to chemotherapy display increased OXPHOS, mitochondrial function, and metabolic flexibility. To exploit this weakness in chemoresistant ovarian cancer cells, we examined the effectiveness of the mitochondrial inhibitor CPI-613 in treating preclinical ovarian cancer.</p><p><strong>Methods: </strong>Chemosensitive OVCAR3, and chemoresistant CAOV3 and F2 ovarian cancer cells lines and their xenografts in nude mice were used. Functional metabolic studies were performed using Seahorse instrument. Metabolite quantification was performed using LC/MS/MS.</p><p><strong>Results: </strong>Mice treated with CPI-613 exhibited a notable increase in overall survival and a reduction in tumor development and burden in OVCAR3, F2, and CAOV3 xenografts. CPI-613 suppressed the activity of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complex, which are two of its targets. This led to a reduction in OXPHOS and tricarboxylic acid cycle activity in all 3 xenografts. The addition of CPI-613 enhanced the responsiveness of chemotherapy in the chemoresistant F2 and CAOV3 tumors, resulting in a notable improvement in survival rates and a reduction in tumor size as compared to using chemotherapy alone. CPI-613 reduced the chemotherapy-induced OXPHOS in chemoresistant tumors. The study revealed that the mechanism by which CPI-613 inhibits tumor growth is through mitochondrial collapse. This is evidenced by an increase in superoxide production within the mitochondria, a decrease in ATP generation, and the release of cytochrome C, which triggers mitochondria-induced apoptosis.</p><p><strong>Conclusion: </strong>Our study demonstrates the translational potential of CPI-613 against chemoresistant ovarian tumors.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"226"},"PeriodicalIF":3.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xueying Cui, Xiaocan Lei, Tao Huang, Xueyan Mao, Zhiwei Shen, Xiuli Yang, Wanting Peng, Jingjing Yu, Shun Zhang, Peng Huo
{"title":"Follicular fluid-derived extracellular vesicles miR-34a-5p regulates granulosa cell glycolysis in polycystic ovary syndrome by targeting LDHA.","authors":"Xueying Cui, Xiaocan Lei, Tao Huang, Xueyan Mao, Zhiwei Shen, Xiuli Yang, Wanting Peng, Jingjing Yu, Shun Zhang, Peng Huo","doi":"10.1186/s13048-024-01542-w","DOIUrl":"10.1186/s13048-024-01542-w","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is highly prevalent in women of reproductive age worldwide, exhibits highly heterogeneous clinical presentation and biochemical parameters, and has no cure. This study aimed to investigate the role of miR-34a-5p in PCOS, its effect on glycolysis in granulosa cells (GCs), and its potential contribution to follicular dysregulation.</p><p><strong>Methods: </strong>Herein, Follicular follicular fluid (FF) samples were collected from six patients with PCOS and six healthy controls undergoing in vitro fertilization-embryo transfer. The isolated extracellular vesicles were characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Additionally, miRNA sequencing was performed to identify differentially expressed microRNAs, and their functions were analyzed through transcriptomics. The In vitro effects of miR-34a-5p on glycolysis, cell proliferation, and apoptosis were assessed in human ovarian granulosa tumour cell line (KGN cells). Targets of miR-34a-5p were identified by dual-luciferase reporter assays, and quantitative real-time polymerase chain reaction and western blotting were performed to determine gene and protein expression.</p><p><strong>Results: </strong>The level of miR-34a-5p in FF-derived extracellular vesicles derived from patients with PCOS was significantly higher than that of the control group. Transcriptomic analysis highlighted miR-34a-5p as a key regulator of glycolysis and apoptosis. Furthermore, in vitro analysis showed that miR-34a-5p targeted lactate dehydrogenase A (LDHA), inhibited glycolysis, reduced energy supply to GCs, and promoted apoptosis of KGN cells. Conversely, miR-34a-5p inhibition restored glycolysis function and cell viability.</p><p><strong>Conclusion: </strong>The findings of this study show that miR-34a-5p mediates GC apoptosis in PCOS by targeting LDHA and inhibiting glycolysis, suggesting its crucial role in PCOS pathophysiology, and offering potential therapeutic targets for improving follicular development and fertility outcomes in patients with PCOS. Further research is needed to explore the clinical implications of miR-34a-5p and its use as a biomarker for early diagnosis and prognosis of PCOS.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"223"},"PeriodicalIF":3.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring lncRNA expression in follicular fluid exosomes of patients with obesity and polycystic ovary syndrome based on high-throughput sequencing technology.","authors":"Xin Xin, Li Dong, Jiaxi Li, Wen Chen, Yue Qiu, Fang Lian, Haicui Wu","doi":"10.1186/s13048-024-01552-8","DOIUrl":"10.1186/s13048-024-01552-8","url":null,"abstract":"<p><strong>Background: </strong>Infertility is a reproductive health problem that attracts worldwide attention. Polycystic ovary syndrome (PCOS) is a major cause of female infertility and patients with obesity and PCOS are particularly common in clinical practice. Long non-coding RNA (lncRNAs) are a functional core in cells that regulate gene expression, transcription, and chromatin modification processes, and participate in epigenetics, cell cycle, and cell differentiation. LncRNAs are assumed to play a role in the occurrence and development of PCOS; however, their specific mechanism of action remains to be elucidated.</p><p><strong>Methods: </strong>High-throughput sequencing technology has been used to sequence and analyze lncRNAs in exosomes from the follicular fluid of patients with obesity and PCOS and those who underwent assisted reproductive therapy owing to male factors. Specific expression profiles of patients with obesity and PCOS were obtained and functional information analysis combined with a literature review were performed to screen for differentially expressed lncRNAs, which were validated using real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>High-throughput sequencing analysis revealed that compared to normal patients with male infertility, patients with obesity and PCOS had a total of 20 lncRNAs with significant expression differences in follicular fluid exosomes. Among them, 17 lncRNAs were upregulated and three were downregulated. Functional analysis showed that differentially expressed genes were mainly enriched in \"cell metabolism,\" \"cell adhesion,\" and other aspects: related gene pathways mainly involved Huntington's disease, Parkinson's disease, spliceosomes, non-alcoholic fatty liver disease, and ribosomes. Verification of differentially expressed lncRNAs revealed that the expression of lncRNAs TPT1-AS1, PTOV1-AS1, PTPRG-AS1, and SNHG14 in follicular fluid exosomes was consistent with the sequencing results.</p><p><strong>Conclusion: </strong>A preliminary differential expression profile of lncRNAs in exosomes of patients with obesity and PCOS was established by transcriptomic analysis of these individuals. Our bioinformatics analysis results may be applicable to further study of the impact mechanism involving obesity and PCOS. These differentially expressed lncRNAs maybe served as potential biomarkers for in-depth studies of the occurrence, development on Follicle quality and function for patients with PCOS in the future.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"220"},"PeriodicalIF":3.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nehal M Elsherbiny, Mohamed S Abdel-Maksoud, Kousalya Prabahar, Zuhair M Mohammedsaleh, Omnia A M Badr, Arigue A Dessouky, Hoda A Salem, Omnia A Refadah, Ayman Samir Farid, Ashraf A Shamaa, Nesrine Ebrahim
{"title":"MSCs-derived EVs protect against chemotherapy-induced ovarian toxicity: role of PI3K/AKT/mTOR axis.","authors":"Nehal M Elsherbiny, Mohamed S Abdel-Maksoud, Kousalya Prabahar, Zuhair M Mohammedsaleh, Omnia A M Badr, Arigue A Dessouky, Hoda A Salem, Omnia A Refadah, Ayman Samir Farid, Ashraf A Shamaa, Nesrine Ebrahim","doi":"10.1186/s13048-024-01545-7","DOIUrl":"10.1186/s13048-024-01545-7","url":null,"abstract":"<p><p>Chemotherapy detrimentally impacts fertility via depletion of follicular reserves in the ovaries leading to ovarian failure (OF) and development of estrogen deficiency-related complications. The currently proposed options to preserve fertility such as Oocyte or ovarian cortex cryopreservation are faced with many technical obstacles that limit their effective implementation. Therefore, developing new modalities to protect ovarian function remains a pending target. Exosomes are nano-sized cell-derived extracellular vesicles (EVs) with documented efficacy in the field of regenerative medicine. The current study sought to determine the potential beneficial effects of mesenchymal stem cells (MSCs)-derived EVs in experimentally induced OF. Female albino rats were randomly allocated to four groups: control, OF group, OF + MSCs-EVs group, OF + Rapamycin (mTOR inhibitor) group, and OF + Quercetin (PI3K/AKT inhibitor) group. Follicular development was assessed via histopathological and immunohistochemical examination, and ovarian function was evaluated by hormonal assay. PI3K/Akt/mTOR signaling pathway as a key modulator of ovarian follicular activation was also assessed. MSCs-EVs administration to OF rats resulted in restored serum hormonal levels, preserved primordial follicles and oocytes, suppressed ovarian PI3K/AKT axis and downstream effectors (mTOR and FOXO3), modulated miRNA that target this axis, decreased expression of ovarian apoptotic markers (BAX, BCl2) and increased expression of proliferation marker Ki67. The present study validated the effectiveness of MSCs-EVs therapy in preventing ovarian insufficiency induced by chemotherapy. Concomitant MSCs-EVs treatment during chemotherapy could significantly preserve ovarian function and fertility by suppressing the PI3K/Akt axis, preventing follicular overactivation, maintaining normal ovarian cellular proliferation, and inhibiting granulosa cell apoptosis.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"222"},"PeriodicalIF":3.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SOX17 expression in ovarian clear cell carcinoma.","authors":"Daichi Kodama, Motoki Takenaka, Chiemi Saigo, Masako Azuma, Yuki Hanamatsu, Masanori Isobe, Tamotsu Takeuchi","doi":"10.1186/s13048-024-01549-3","DOIUrl":"10.1186/s13048-024-01549-3","url":null,"abstract":"<p><p>Recent studies have revealed that the Sry-related HMG box gene 17 (SOX17) plays an important role in ovarian carcinogenesis. Unlike other types of ovarian cancer, ovarian clear cell carcinoma (OCCC) has a distinct pathobiological phenotype, often harboring an AT-rich interaction domain 1 A (ARID1A) mutation. In the present study, to determine the SOX17 in OCCC cells, we immunohistochemically examined SOX17 expression in 47 whole-tissue specimens of OCCC. Although not statistically significant, SOX17-high immunoreactivity tended to be related to unfavorable patient outcomes. We also aimed to determine the relationship of SOX17 with ARID1A. Double immunofluorescence staining demonstrated that SOX17 immunoreactivity was not associated with ARID1A immunoreactivity. Immunoblotting revealed that SOX17 was abundantly expressed in cultured OVISE and RMG-V OCCC cells, but not in OVTOKO OCCC cells. Polyubiquitinated bands of SOX17 were observed in MG132 treated OVTOKO, but not in OVISE or RMG-V OCCC cells. Notably, si-RNA-mediated knockdown of a deubiquitinase enzyme, ubiquitin C-terminal hydrolase L1, increased polyubiquitination followed by proteasome degradation of SOX17 in OVISE. These findings indicate that SOX17 is not uniformly and heterogeneously expressed in OCCCs, independent of ARID1A deficiency. Impaired ubiquitin-mediated proteasome degradation may stabilize SOX17 in some OCCC cells.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"221"},"PeriodicalIF":3.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Machine learning models in evaluating the malignancy risk of ovarian tumors: a comparative study.","authors":"Xin He, Xiang-Hui Bai, Hui Chen, Wei-Wei Feng","doi":"10.1186/s13048-024-01544-8","DOIUrl":"10.1186/s13048-024-01544-8","url":null,"abstract":"<p><strong>Objectives: </strong>The study aimed to compare the diagnostic efficacy of the machine learning models with expert subjective assessment (SA) in assessing the malignancy risk of ovarian tumors using transvaginal ultrasound (TVUS).</p><p><strong>Methods: </strong>The retrospective single-center diagnostic study included 1555 consecutive patients from January 2019 to May 2021. Using this dataset, Residual Network(ResNet), Densely Connected Convolutional Network(DenseNet), Vision Transformer(ViT), and Swin Transformer models were established and evaluated separately or combined with Cancer antigen 125 (CA 125). The diagnostic performance was then compared with SA.</p><p><strong>Results: </strong>Of the 1555 patients, 76.9% were benign, while 23.1% were malignant (including borderline). When differentiating the malignant from ovarian tumors, the SA had an AUC of 0.97 (95% CI, 0.93-0.99), sensitivity of 87.2%, and specificity of 98.4%. Except for Vision Transformer, other machine learning models had diagnostic performance comparable to that of the expert. The DenseNet model had an AUC of 0.91 (95% CI, 0.86-0.95), sensitivity of 84.6%, and specificity of 95.1%. The ResNet50 model had an AUC of 0.91 (0.85-0.95). The Swin Transformer model had an AUC of 0.92 (0.87-0.96), sensitivity of 87.2%, and specificity of 94.3%. There was a statistically significant difference between the Vision Transformer and SA, and between the Vision Transformer and Swin Transformer models (AUC: 0.87 vs. 0.97, P = 0.01; AUC: 0.87 vs. 0.92, P = 0.04). Adding CA125 did not improve the diagnostic performance of the models in distinguishing benign and malignant ovarian tumors.</p><p><strong>Conclusion: </strong>The deep learning model of TVUS can be used in ovarian cancer evaluation, and its diagnostic performance is comparable to that of expert assessment.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"219"},"PeriodicalIF":3.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aravindan Narayanan, Ankita S More, Muskan Talreja, Avinash M Mali, Sannannagari Boya Vinay, Sharmila A Bapat
{"title":"A novel ITGB8 transcript variant sustains ovarian cancer cell survival through genomic instability and altered ploidy on a mutant p53 background.","authors":"Aravindan Narayanan, Ankita S More, Muskan Talreja, Avinash M Mali, Sannannagari Boya Vinay, Sharmila A Bapat","doi":"10.1186/s13048-024-01538-6","DOIUrl":"10.1186/s13048-024-01538-6","url":null,"abstract":"<p><strong>Background: </strong>Transcript variants and protein isoforms are central to unique tissue functions and maintenance of homeostasis, in addition to being associated with aberrant states such as cancer, where their crosstalk with the mutated tumor suppressor p53 may contribute to genomic instability and chromosomal rearrangements. We previously identified several novel splice variants in ovarian cancer RNA-sequencing datasets; herein, we aimed to elucidate the biological effects of the Integrin Subunit Beta 8 variant (termed pITGB8-205).</p><p><strong>Methods: </strong>Resolution of the full-length sequence of pITGB8-205 through rapid amplification of cDNA ends (RACE-PCR). Cell cycle analysis and karyotype studies were performed to further explore genomic instability. RNA-seq and proteomics analyses were used to identify the differential expression of the genes.</p><p><strong>Results: </strong>This full-length study revealed a unique 5' sequence in pITGB8-205 that differed from the reported ITGB8-205 sequence, suggesting differential regulation of this novel transcript. Under a p53 mutant background, overexpression of pITGB8-205 triggered genetic instability reminiscent of oncogene-induced replicative stress with extensive abnormal mitoses and chromosomal and nuclear aberrations indicative of chromosomal instability, leading to near whole-genome duplication that imposes energy stress on cellular resources. Micronuclei and aneuploidy are striking features of pITGB8-205-overexpressing p53-mutant cells but are not enhanced in p53 wild-type (WT) cells. RNA-seq and proteomics analyses further suggested that p53 inactivation in ovarian cancer provides a permissive intracellular molecular niche for pITGB8-205 to mediate its effects on genomic instability. This observation is pivotal considering that most high-grade serous ovarian carcinoma (HGSC) tumors express mutant p53. The resulting aneuploid clones with enhanced self-renewal and survival capabilities disrupt clonal dominance under stress yet maintain a balance between replicative stress and prosurvival advantages.</p><p><strong>Conclusion: </strong>pITGB8-205-overexpressing clones sustain ovarian tumor cell survival, achieve homeostasis and are formidable opponents of therapy.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"218"},"PeriodicalIF":3.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiandan Zhang, Xuan Wang, Hao Li, Haihong Wang, Dewei Du, Huijuan Huang
{"title":"ATF3 mediates PM2.5-induced apoptosis and inflammation in ovarian granulosa cells.","authors":"Xiandan Zhang, Xuan Wang, Hao Li, Haihong Wang, Dewei Du, Huijuan Huang","doi":"10.1186/s13048-024-01539-5","DOIUrl":"10.1186/s13048-024-01539-5","url":null,"abstract":"<p><p>Particulate matter 2.5 (PM2.5) pollution has emerged as a major global public health concern because of its adverse effects on human health. Our group has previously demonstrated that PM2.5 exposure can seriously impair ovarian function. However, the underlying mechanisms remain a mystery. This study verifies ovarian damage in mice, evidenced by inflammatory cell infiltration and follicular atresia, following 5 months of PM2.5 exposure via tracheal drip (35 µg/m³ for low dose and 150 µg/m³ for high dose). In addition, PM2.5 exposure inhibited the cell viability of human granulosa cells (KGN) and induced apoptosis at the concentrations of 50, 100, and 150 µg/mL for 24 h. The apoptosis of KGN cells induced by inflammation contributes to follicular atresia. Furthermore, we conducted RNA-sequencing analysis to identify the genes and pathways triggered by PM2.5 (100 µg/mL) exposure, which decreases the KGN cell viability. We found a significant increase in Activating Transcription Factor 3 (ATF3). Further mechanistic studies reveal a strong association between PM2.5-induced apoptosis, inflammation, and ATF3 with its downstream oxidative stress signals. In summary, the ATF3 pathway serves a vital role in the ovarian injury caused by PM2.5 exposures.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"215"},"PeriodicalIF":3.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Implication of vasopressin receptor genes (AVPR1A and AVPR1B) in the susceptibility to polycystic ovary syndrome.","authors":"Pruthvi Goparaju, Claudia Gragnoli","doi":"10.1186/s13048-024-01515-z","DOIUrl":"10.1186/s13048-024-01515-z","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a complex heterogenous disorder manifesting with various reproductive, endocrine, and metabolic derangements such as insulin resistance and hyperglycemia. The arginine vasopressin peptide (AVP), also called or antidiuretic hormone (ADH), modulates metabolic functions such as glucose hemostasis, insulin sensitivity, and lipid metabolism via binding to two central and peripheral receptors (AVPR1A and AVPR1B). In the present study, we aimed to detect whether the AVPR1A and AVPR1B genes confer risk for PCOS.</p><p><strong>Methods: </strong>In peninsular Italian families, we tested 7 variants in the AVPR1B gene and 2 variants in the AVPR1A gene via Pseudomarker for linkage and linkage joint to association (i.e.., linkage disequilibrium) with PCOS.</p><p><strong>Results: </strong>We identified two risk variants in each gene, significantly associated with the risk of PCOS.</p><p><strong>Conclusion: </strong>To the best of our knowledge, this is the first study to report risk variants in AVPR1A and AVPR1B genes in association with PCOS. However, replication in other ethnic groups as well as functional studies are needed to confirm these results.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"17 1","pages":"214"},"PeriodicalIF":3.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}