Pub Date : 2024-05-08DOI: 10.1186/s13048-024-01404-5
Yuxi Li, Hsun-Ming Chang, Hua Zhu, Ying-Pu Sun, Peter C K Leung
The epidermal growth factor (EGF)-like factors, comprising amphiregulin (AREG), betacellulin (BTC), and epiregulin (EREG), play a critical role in regulating the ovulatory process. Pentraxin 3 (PTX3), an essential ovulatory protein, is necessary for maintaining extracellular matrix (ECM) stability during cumulus expansion. The aim of this study was to investigate the impact of EGF-like factors, AREG, BTC, and EREG on the expression and production of PTX3 in human granulosa-lutein (hGL) cells and the molecular mechanisms involved. Our results demonstrated that AREG, BTC, and EREG could regulate follicular function by upregulating the expression and increasing the production of PTX3 in both primary (obtained from 20 consenting patients undergoing IVF treatment) and immortalized hGL cells. The upregulation of PTX3 expression was primarily facilitated by the activation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathway, induced by these EGF-like factors. In addition, we found that the upregulation of PTX3 expression triggered by the EGF-like factors was completely reversed by either pretreatment with the epidermal growth factor receptor (EGFR) inhibitor, AG1478, or knockdown of EGFR, suggesting that EGFR is crucial for activating the ERK1/2 signaling pathway in hGL cells. Overall, our findings indicate that AREG, BTC, and EREG may modulate human cumulus expansion during the periovulatory stage through the upregulation of PTX3.
{"title":"EGF-like growth factors upregulate pentraxin 3 expression in human granulosa-lutein cells.","authors":"Yuxi Li, Hsun-Ming Chang, Hua Zhu, Ying-Pu Sun, Peter C K Leung","doi":"10.1186/s13048-024-01404-5","DOIUrl":"10.1186/s13048-024-01404-5","url":null,"abstract":"<p><p>The epidermal growth factor (EGF)-like factors, comprising amphiregulin (AREG), betacellulin (BTC), and epiregulin (EREG), play a critical role in regulating the ovulatory process. Pentraxin 3 (PTX3), an essential ovulatory protein, is necessary for maintaining extracellular matrix (ECM) stability during cumulus expansion. The aim of this study was to investigate the impact of EGF-like factors, AREG, BTC, and EREG on the expression and production of PTX3 in human granulosa-lutein (hGL) cells and the molecular mechanisms involved. Our results demonstrated that AREG, BTC, and EREG could regulate follicular function by upregulating the expression and increasing the production of PTX3 in both primary (obtained from 20 consenting patients undergoing IVF treatment) and immortalized hGL cells. The upregulation of PTX3 expression was primarily facilitated by the activation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathway, induced by these EGF-like factors. In addition, we found that the upregulation of PTX3 expression triggered by the EGF-like factors was completely reversed by either pretreatment with the epidermal growth factor receptor (EGFR) inhibitor, AG1478, or knockdown of EGFR, suggesting that EGFR is crucial for activating the ERK1/2 signaling pathway in hGL cells. Overall, our findings indicate that AREG, BTC, and EREG may modulate human cumulus expansion during the periovulatory stage through the upregulation of PTX3.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892037","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}
Background: Recent studies have revealed the correlation between serum vitamin D (VD) level and polycystic ovary syndrome (PCOS), but the causality and specific mechanisms remain uncertain.
Objective: We aimed to investigate the cause-effect relationship between serum VD and PCOS, and the role of testosterone in the related pathological mechanisms.
Methods: We assessed the causality between serum VD and PCOS by using genome-wide association studies (GWAS) data in a bidirectional two-sample Mendelian randomization (TS-MR) analysis. Subsequently, a MR mediation analysis was conducted to examine the mediating action of testosterone in the causality between serum VD and PCOS. Ultimately, we integrated GWAS data with cis-expression quantitative loci (cis-eQTLs) data for gene annotation, and used the potentially related genes for functional enrichment analysis to assess the involvement of testosterone and the potential mechanisms.
Results: TS-MR analysis showed that individuals with lower level of serum VD were more likely to develop PCOS (OR = 0.750, 95% CI: 0.587-0.959, P = 0.022). MR mediation analysis uncovered indirect causal effect of serum VD level on the risk of PCOS via testosterone (OR = 0.983, 95% CI: 0.968-0.998, P = 0.025). Functional enrichment analysis showed that several pathways may be involved in the VD-testosterone-PCOS axis, such as steroid hormone biosynthesis and autophagy process.
Conclusion: Our findings suggest that genetically predicted lower serum VD level may cause a higher risk of developing PCOS, which may be mediated by increased testosterone production.
{"title":"Causal association between low vitamin D and polycystic ovary syndrome: a bidirectional mendelian randomization study.","authors":"Bingrui Gao, Chenxi Zhang, Deping Wang, Bojuan Li, Zhongyan Shan, Weiping Teng, Jing Li","doi":"10.1186/s13048-024-01420-5","DOIUrl":"10.1186/s13048-024-01420-5","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have revealed the correlation between serum vitamin D (VD) level and polycystic ovary syndrome (PCOS), but the causality and specific mechanisms remain uncertain.</p><p><strong>Objective: </strong>We aimed to investigate the cause-effect relationship between serum VD and PCOS, and the role of testosterone in the related pathological mechanisms.</p><p><strong>Methods: </strong>We assessed the causality between serum VD and PCOS by using genome-wide association studies (GWAS) data in a bidirectional two-sample Mendelian randomization (TS-MR) analysis. Subsequently, a MR mediation analysis was conducted to examine the mediating action of testosterone in the causality between serum VD and PCOS. Ultimately, we integrated GWAS data with cis-expression quantitative loci (cis-eQTLs) data for gene annotation, and used the potentially related genes for functional enrichment analysis to assess the involvement of testosterone and the potential mechanisms.</p><p><strong>Results: </strong>TS-MR analysis showed that individuals with lower level of serum VD were more likely to develop PCOS (OR = 0.750, 95% CI: 0.587-0.959, P = 0.022). MR mediation analysis uncovered indirect causal effect of serum VD level on the risk of PCOS via testosterone (OR = 0.983, 95% CI: 0.968-0.998, P = 0.025). Functional enrichment analysis showed that several pathways may be involved in the VD-testosterone-PCOS axis, such as steroid hormone biosynthesis and autophagy process.</p><p><strong>Conclusion: </strong>Our findings suggest that genetically predicted lower serum VD level may cause a higher risk of developing PCOS, which may be mediated by increased testosterone production.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11077756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876690","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}
Pub Date : 2024-05-04DOI: 10.1186/s13048-024-01421-4
Cassie Liu, Makenzie Vorderbruggen, Catalina Muñoz-Trujillo, Sung Hoon Kim, John A. Katzenellenbogen, Benita S. Katzenellenbogen, Adam R. Karpf
Genetic studies implicate the oncogenic transcription factor Forkhead Box M1 (FOXM1) as a potential therapeutic target in high-grade serous ovarian cancer (HGSOC). We evaluated the activity of different FOXM1 inhibitors in HGSOC cell models. We treated HGSOC and fallopian tube epithelial (FTE) cells with a panel of previously reported FOXM1 inhibitors. Based on drug potency, efficacy, and selectivity, determined through cell viability assays, we focused on two compounds, NB-73 and NB-115 (NB compounds), for further investigation. NB compounds potently and selectively inhibited FOXM1 with lesser effects on other FOX family members. NB compounds decreased FOXM1 expression via targeting the FOXM1 protein by promoting its proteasome-mediated degradation, and effectively suppressed FOXM1 gene targets at both the protein and mRNA level. At the cellular level, NB compounds promoted apoptotic cell death. Importantly, while inhibition of apoptosis using a pan-caspase inhibitor rescued HGSOC cells from NB compound-induced cell death, it did not rescue FOXM1 protein degradation, supporting that FOXM1 protein loss from NB compound treatment is specific and not a general consequence of cytotoxicity. Drug washout studies indicated that FOXM1 reduction was retained for at least 72 h post-treatment, suggesting that NB compounds exhibit long-lasting effects in HGSOC cells. NB compounds effectively suppressed both two-dimensional and three-dimensional HGSOC cell colony formation at sub-micromolar concentrations. Finally, NB compounds exhibited synergistic activity with carboplatin in HGSOC cells. NB compounds are potent, selective, and efficacious inhibitors of FOXM1 in HGSOC cells and are worthy of further investigation as HGSOC therapeutics.
{"title":"NB compounds are potent and efficacious FOXM1 inhibitors in high-grade serous ovarian cancer cells","authors":"Cassie Liu, Makenzie Vorderbruggen, Catalina Muñoz-Trujillo, Sung Hoon Kim, John A. Katzenellenbogen, Benita S. Katzenellenbogen, Adam R. Karpf","doi":"10.1186/s13048-024-01421-4","DOIUrl":"https://doi.org/10.1186/s13048-024-01421-4","url":null,"abstract":"Genetic studies implicate the oncogenic transcription factor Forkhead Box M1 (FOXM1) as a potential therapeutic target in high-grade serous ovarian cancer (HGSOC). We evaluated the activity of different FOXM1 inhibitors in HGSOC cell models. We treated HGSOC and fallopian tube epithelial (FTE) cells with a panel of previously reported FOXM1 inhibitors. Based on drug potency, efficacy, and selectivity, determined through cell viability assays, we focused on two compounds, NB-73 and NB-115 (NB compounds), for further investigation. NB compounds potently and selectively inhibited FOXM1 with lesser effects on other FOX family members. NB compounds decreased FOXM1 expression via targeting the FOXM1 protein by promoting its proteasome-mediated degradation, and effectively suppressed FOXM1 gene targets at both the protein and mRNA level. At the cellular level, NB compounds promoted apoptotic cell death. Importantly, while inhibition of apoptosis using a pan-caspase inhibitor rescued HGSOC cells from NB compound-induced cell death, it did not rescue FOXM1 protein degradation, supporting that FOXM1 protein loss from NB compound treatment is specific and not a general consequence of cytotoxicity. Drug washout studies indicated that FOXM1 reduction was retained for at least 72 h post-treatment, suggesting that NB compounds exhibit long-lasting effects in HGSOC cells. NB compounds effectively suppressed both two-dimensional and three-dimensional HGSOC cell colony formation at sub-micromolar concentrations. Finally, NB compounds exhibited synergistic activity with carboplatin in HGSOC cells. NB compounds are potent, selective, and efficacious inhibitors of FOXM1 in HGSOC cells and are worthy of further investigation as HGSOC therapeutics.","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140839858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Following publication of the original article [1], the authors reported that there was an error in the additional file 1 wherein during compilation of the figure, images from incorrect group were inadvertently included in the panel of “TP63-WT+siCLCA2-1”. The correct images were shown below.
Incorrect additional file:
Correct additional file:
The original article has been corrected.
Fan Y, Chen S, Chu C, et al. TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2. J Ovarian Res. 2024;17:67. https://doi.org/10.1186/s13048-024-01396-2.
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Authors and Affiliations
Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100006, China
Yali Fan, Shuya Chen, Ruixia Liu, Lin Li & Chenghong Yin
Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, China
Chunfang Chu
Department of Traditional Chinese Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, China
Xiaodan Yin & Mingwei Xin
Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, China
Jing Jin
Department of Gynaecology and Obstetrics, Beijing F
更正:J Ovarian Res 17, 67 (2024)https://doi.org/10.1186/s13048-024-01396-2Following 原文[1]发表后,作者报告说附加文件1中有一处错误,即在编译图表时,"TP63-WT+siCLCA2-1 "面板中无意中包含了错误组的图像。错误的附加文件:正确的附加文件:原文已更正。Fan Y, Chen S, Chu C, et al. TP63截短突变通过增强CLCA2的转录激活导致细胞凋亡增加和卵巢早衰。J Ovarian Res. 2024;17:67. https://doi.org/10.1186/s13048-024-01396-2.文章 CAS PubMed PubMed Central Google Scholar 下载参考文献作者及单位首都医科大学附属北京妇产医院中心实验室,北京市妇幼保健院,北京,100006范亚丽,陈舒雅,刘瑞霞,李琳&;尹成红 首都医科大学附属北京妇产医院妇科,北京,100026 褚春芳 首都医科大学附属北京妇产医院中医科,北京,100026 尹晓丹 &;首都医科大学附属北京妇产医院、北京市妇幼保健院妇科内分泌科,北京,100026 金晶 首都医科大学附属北京友谊医院妇产科,北京,100050 张凌燕 首都医科大学附属北京妇产医院、北京市妇幼保健院产科、首都医科大学附属北京妇产医院产科 闫慧慧 首都医科大学附属北京妇产医院检验科 100026、中国Zheng Cao作者Yali Fan查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者Shuya Chen查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者Chunfang Chu查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者ScholarXiaodan YinView 作者发表作品您也可以在 PubMed Google ScholarJing JinView 作者发表作品您也可以在 PubMed Google ScholarLingyan ZhangView 作者发表作品您也可以在 PubMed Google ScholarHuihui YanView发表文章 您也可以在PubMed Google Scholar中搜索该作者Zheng Cao发表文章 您也可以在PubMed Google Scholar中搜索该作者Ruixia Liu发表文章 您也可以在PubMed Google Scholar中搜索该作者Mingwei Xin发表文章 您也可以在PubMed Google Scholar中搜索该作者Mingwei Xin发表文章 您也可以在PubMed Google Scholar中搜索该作者Mingwei Xin发表文章您也可以在 PubMed Google Scholar中搜索该作者Lin Li查看作者发表的论文您也可以在 PubMed Google Scholar中搜索该作者Chenghong Yin查看作者发表的论文您也可以在 PubMed Google Scholar中搜索该作者通讯作者Mingwei Xin、Lin Li 或 Chenghong Yin。开放存取 本文采用知识共享署名 4.0 国际许可协议进行许可,该协议允许以任何媒介或格式使用、共享、改编、分发和复制本文,但必须注明原作者和出处,提供知识共享许可协议的链接,并说明是否进行了修改。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中,除非在材料的署名栏中另有说明。如果材料未包含在文章的知识共享许可协议中,且您打算使用的材料不符合法律规定或超出许可使用范围,您需要直接从版权所有者处获得许可。要查看该许可的副本,请访问 http://creativecommons.org/licenses/by/4.0/。除非在数据的信用行中另有说明,否则知识共享公共领域专用免责声明 (http://creativecommons.org/publicdomain/zero/1.0/) 适用于本文提供的数据。转载与许可引用本文Fan, Y., Chen, S., Chu, C. et al. Correction:TP63截短突变通过增强CLCA2的转录激活导致细胞凋亡增加和卵巢早衰。J Ovarian Res 17, 93 (2024). https://doi.org/10.1186/s13048-024-01418-zDownload citationPublished: 29 April 2024DOI: https://doi.org/10.1186/s13048-024-01418-zShare this articleAnyone you share the following link with will be able to read this content:获取可共享链接很抱歉,本文目前没有可共享链接。
{"title":"Correction: TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2","authors":"Yali Fan, Shuya Chen, Chunfang Chu, Xiaodan Yin, Jing Jin, Lingyan Zhang, Huihui Yan, Zheng Cao, Ruixia Liu, Mingwei Xin, Lin Li, Chenghong Yin","doi":"10.1186/s13048-024-01418-z","DOIUrl":"https://doi.org/10.1186/s13048-024-01418-z","url":null,"abstract":"<p><b>Correction</b><b>: </b><b>J Ovarian Res 17, 67 (2024)</b></p><p><b>https://doi.org/10.1186/s13048-024-01396-2</b></p><br/><p>Following publication of the original article [1], the authors reported that there was an error in the additional file 1 wherein during compilation of the figure, images from incorrect group were inadvertently included in the panel of “TP63-WT+siCLCA2-1”. The correct images were shown below.</p><p>Incorrect additional file:</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13048-024-01418-z/MediaObjects/13048_2024_1418_Figa_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure a\" aria-describedby=\"Figa\" height=\"1124\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13048-024-01418-z/MediaObjects/13048_2024_1418_Figa_HTML.png\" width=\"685\"/></picture></figure><p>Correct additional file:</p><figure><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13048-024-01418-z/MediaObjects/13048_2024_1418_Figb_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure b\" aria-describedby=\"Figb\" height=\"1135\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13048-024-01418-z/MediaObjects/13048_2024_1418_Figb_HTML.png\" width=\"685\"/></picture></figure><p>The original article has been corrected.</p><ol data-track-component=\"outbound reference\"><li data-counter=\"1.\"><p>Fan Y, Chen S, Chu C, et al. TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2. J Ovarian Res. 2024;17:67. https://doi.org/10.1186/s13048-024-01396-2.</p><p>Article CAS PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100006, China</p><p>Yali Fan, Shuya Chen, Ruixia Liu, Lin Li & Chenghong Yin</p></li><li><p>Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, China</p><p>Chunfang Chu</p></li><li><p>Department of Traditional Chinese Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, China</p><p>Xiaodan Yin & Mingwei Xin</p></li><li><p>Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, China</p><p>Jing Jin</p></li><li><p>Department of Gynaecology and Obstetrics, Beijing F","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140812636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-29DOI: 10.1186/s13048-024-01419-y
Feng Zhan, Yina Guo, Lidan He
This study aims to explore the contribution of differentially expressed programmed cell death genes (DEPCDGs) to the heterogeneity of serous ovarian cancer (SOC) through single-cell RNA sequencing (scRNA-seq) and assess their potential as predictors for clinical prognosis. SOC scRNA-seq data were extracted from the Gene Expression Omnibus database, and the principal component analysis was used for cell clustering. Bulk RNA-seq data were employed to analyze SOC-associated immune cell subsets key genes. CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) were utilized to calculate immune cell scores. Prognostic models and nomograms were developed through univariate and multivariate Cox analyses. Our analysis revealed that 48 DEPCDGs are significantly correlated with apoptotic signaling and oxidative stress pathways and identified seven key DEPCDGs (CASP3, GADD45B, GNA15, GZMB, IL1B, ISG20, and RHOB) through survival analysis. Furthermore, eight distinct cell subtypes were characterized using scRNA-seq. It was found that G protein subunit alpha 15 (GNA15) exhibited low expression across these subtypes and a strong association with immune cells. Based on the DEGs identified by the GNA15 high- and low-expression groups, a prognostic model comprising eight genes with significant prognostic value was constructed, effectively predicting patient overall survival. Additionally, a nomogram incorporating the RS signature, age, grade, and stage was developed and validated using two large SOC datasets. GNA15 emerged as an independent and excellent prognostic marker for SOC patients. This study provides valuable insights into the prognostic potential of DEPCDGs in SOC, presenting new avenues for personalized treatment strategies.
{"title":"A novel defined programmed cell death related gene signature for predicting the prognosis of serous ovarian cancer","authors":"Feng Zhan, Yina Guo, Lidan He","doi":"10.1186/s13048-024-01419-y","DOIUrl":"https://doi.org/10.1186/s13048-024-01419-y","url":null,"abstract":"This study aims to explore the contribution of differentially expressed programmed cell death genes (DEPCDGs) to the heterogeneity of serous ovarian cancer (SOC) through single-cell RNA sequencing (scRNA-seq) and assess their potential as predictors for clinical prognosis. SOC scRNA-seq data were extracted from the Gene Expression Omnibus database, and the principal component analysis was used for cell clustering. Bulk RNA-seq data were employed to analyze SOC-associated immune cell subsets key genes. CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) were utilized to calculate immune cell scores. Prognostic models and nomograms were developed through univariate and multivariate Cox analyses. Our analysis revealed that 48 DEPCDGs are significantly correlated with apoptotic signaling and oxidative stress pathways and identified seven key DEPCDGs (CASP3, GADD45B, GNA15, GZMB, IL1B, ISG20, and RHOB) through survival analysis. Furthermore, eight distinct cell subtypes were characterized using scRNA-seq. It was found that G protein subunit alpha 15 (GNA15) exhibited low expression across these subtypes and a strong association with immune cells. Based on the DEGs identified by the GNA15 high- and low-expression groups, a prognostic model comprising eight genes with significant prognostic value was constructed, effectively predicting patient overall survival. Additionally, a nomogram incorporating the RS signature, age, grade, and stage was developed and validated using two large SOC datasets. GNA15 emerged as an independent and excellent prognostic marker for SOC patients. This study provides valuable insights into the prognostic potential of DEPCDGs in SOC, presenting new avenues for personalized treatment strategies.","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140812748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-27DOI: 10.1186/s13048-024-01422-3
Arash Abdi, Mina Ranjbaran, Fardin Amidi, Fariba Akhondzadeh, Behjat Seifi
The present study aimed to elucidate how mesenchymal stem cells (MSCs) application could efficiently attenuate pathological changes of letrozole-induced poly cystic ovary syndrome (PCOS) by modulating mitochondrial dynamic via PI3K-AKT pathway. Thirty-two female rats were randomly divided into four experimental groups: Sham, PCOS, PCOS + MSCs, and PCOS + MSCs + LY294002. The Sham group received 0.5% w/v carboxymethyl cellulose (CMC); the PCOS group received letrozole (1 mg/kg, daily) in 0.5% CMC for 21 days. Animals in the PCOS + MSCs group received 1 × 106 MSCs/rat (i.p,) on the 22th day of the study. In the PCOS + MSCs + LY294002 group, rats received LY294002 (PI3K-AKT inhibitor) 40 min before MSC transplantation. Mitochondrial dynamic gene expression, mitochondrial membrane potential (MMP), citrate synthase (CS) activity, oxidative stress, inflammation, ovarian histological parameters, serum hormone levels, homeostatic model assessment for insulin resistance (HOMA-IR), insulin and glucose concentrations, p-PI3K and p-AKT protein levels were evaluated at the end of the experiment. PCOS rats showed a significant disruption of mitochondrial dynamics and histological changes, lower MMP, CS, ovary super oxide dismutase (SOD) and estrogen level. They also had a notable rise in insulin and glucose concentrations, HOMA-IR, testosterone level, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, ovarian malondialdehyde (MDA) content as well as a notable decrease in p-PI3K and p-AKT protein levels compared to the Sham group. In the PCOS + MSCs group, the transplantation of MSCs could improve the above parameters. Administration of LY294002 (PI3K-AKT pathway inhibitor) deteriorated mitochondrial dynamic markers, oxidative stress status, inflammation markers, hormonal levels, glucose, and insulin levels and follicular development compared to the PCOS + MSCs group. This study demonstrated that the protective effects of MSC transplantation in regulating mitochondrial dynamics, promoting mitochondrial biogenesis, competing with redox status and inflammation response were mainly mediated through the PI3K-AKT pathway in the PCOS model.
{"title":"The effect of adipose-derived mesenchymal stem cell transplantation on ovarian mitochondrial dysfunction in letrozole-induced polycystic ovary syndrome in rats: the role of PI3K-AKT signaling pathway","authors":"Arash Abdi, Mina Ranjbaran, Fardin Amidi, Fariba Akhondzadeh, Behjat Seifi","doi":"10.1186/s13048-024-01422-3","DOIUrl":"https://doi.org/10.1186/s13048-024-01422-3","url":null,"abstract":"The present study aimed to elucidate how mesenchymal stem cells (MSCs) application could efficiently attenuate pathological changes of letrozole-induced poly cystic ovary syndrome (PCOS) by modulating mitochondrial dynamic via PI3K-AKT pathway. Thirty-two female rats were randomly divided into four experimental groups: Sham, PCOS, PCOS + MSCs, and PCOS + MSCs + LY294002. The Sham group received 0.5% w/v carboxymethyl cellulose (CMC); the PCOS group received letrozole (1 mg/kg, daily) in 0.5% CMC for 21 days. Animals in the PCOS + MSCs group received 1 × 106 MSCs/rat (i.p,) on the 22th day of the study. In the PCOS + MSCs + LY294002 group, rats received LY294002 (PI3K-AKT inhibitor) 40 min before MSC transplantation. Mitochondrial dynamic gene expression, mitochondrial membrane potential (MMP), citrate synthase (CS) activity, oxidative stress, inflammation, ovarian histological parameters, serum hormone levels, homeostatic model assessment for insulin resistance (HOMA-IR), insulin and glucose concentrations, p-PI3K and p-AKT protein levels were evaluated at the end of the experiment. PCOS rats showed a significant disruption of mitochondrial dynamics and histological changes, lower MMP, CS, ovary super oxide dismutase (SOD) and estrogen level. They also had a notable rise in insulin and glucose concentrations, HOMA-IR, testosterone level, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, ovarian malondialdehyde (MDA) content as well as a notable decrease in p-PI3K and p-AKT protein levels compared to the Sham group. In the PCOS + MSCs group, the transplantation of MSCs could improve the above parameters. Administration of LY294002 (PI3K-AKT pathway inhibitor) deteriorated mitochondrial dynamic markers, oxidative stress status, inflammation markers, hormonal levels, glucose, and insulin levels and follicular development compared to the PCOS + MSCs group. This study demonstrated that the protective effects of MSC transplantation in regulating mitochondrial dynamics, promoting mitochondrial biogenesis, competing with redox status and inflammation response were mainly mediated through the PI3K-AKT pathway in the PCOS model.","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140806043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu Linzhu (YLZ) is a classical Chinese traditional formula, which has been used for more than 600 years to regulate menstruation to help pregnancy. However, the mechanism of modern scientific action of YLZ needs to be further studied. Thirty SD female rats were divided into three groups to prepare the blank serum and drug-containing serum, and then using UHPLC-QE-MS to identify the ingredients of YLZ and its drug-containing serum. Twenty-four SD female rats were divided into four groups, except the control group, 4-vinylcyclohexene dicycloxide (VCD) was intraperitoneally injected to establish a primary ovarian insufficiency (POI) model of all groups. Using vaginal smear to show that the estrous cycle of rats was disturbed after modeling, indicates that the POI model was successfully established. The ELISA test was used to measure the follicle-stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH) levels in the serum of rats. HE stain was used to assess the morphology of ovarian tissue. The localization and relative expression levels of CX43 protein were detected by tissue immunofluorescence. Primary ovarian granulosa cells (GCs) were identified by cellular immunofluorescence. CCK8 was used to screen time and concentration of drug-containing serum and evaluate the proliferation effect of YLZ on VCD-induced GCs. ATP kit and Seahorse XFe24 were used to detect energy production and real-time glycolytic metabolism rate of GCs. mRNA and protein expression levels of HIF1α, CX43, PEK, LDH, HK1 were detected by RT-PCR and WB. UHPLC-QE-MS found 1702 ingredients of YLZ and 80 constituents migrating to blood. YLZ reduced the FSH while increasing the AMH and E2 levels. In ovarian tissues, YLZ improved ovarian morphology, follicle development, and the relative expression of CX43. In vitro studies, we found that YLZ increased the proliferative activity of GCs, ATP levels, glycolytic metabolic rate, HIF1α, CX43, PEK, HK1, LDH mRNA, and protein levels. The study indicated that YLZ increased the proliferation and glycolytic energy metabolism of GCs to improve follicular development further alleviating ovarian function.
{"title":"Yu Linzhu alleviates primary ovarian insufficiency in a rat model by improving proliferation and energy metabolism of granulosa cells through hif1α/cx43 pathway","authors":"Xin Ruan, Pengxu Wang, Maolin Wei, Qingqing Yang, Xiaoying Dong","doi":"10.1186/s13048-024-01408-1","DOIUrl":"https://doi.org/10.1186/s13048-024-01408-1","url":null,"abstract":"Yu Linzhu (YLZ) is a classical Chinese traditional formula, which has been used for more than 600 years to regulate menstruation to help pregnancy. However, the mechanism of modern scientific action of YLZ needs to be further studied. Thirty SD female rats were divided into three groups to prepare the blank serum and drug-containing serum, and then using UHPLC-QE-MS to identify the ingredients of YLZ and its drug-containing serum. Twenty-four SD female rats were divided into four groups, except the control group, 4-vinylcyclohexene dicycloxide (VCD) was intraperitoneally injected to establish a primary ovarian insufficiency (POI) model of all groups. Using vaginal smear to show that the estrous cycle of rats was disturbed after modeling, indicates that the POI model was successfully established. The ELISA test was used to measure the follicle-stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH) levels in the serum of rats. HE stain was used to assess the morphology of ovarian tissue. The localization and relative expression levels of CX43 protein were detected by tissue immunofluorescence. Primary ovarian granulosa cells (GCs) were identified by cellular immunofluorescence. CCK8 was used to screen time and concentration of drug-containing serum and evaluate the proliferation effect of YLZ on VCD-induced GCs. ATP kit and Seahorse XFe24 were used to detect energy production and real-time glycolytic metabolism rate of GCs. mRNA and protein expression levels of HIF1α, CX43, PEK, LDH, HK1 were detected by RT-PCR and WB. UHPLC-QE-MS found 1702 ingredients of YLZ and 80 constituents migrating to blood. YLZ reduced the FSH while increasing the AMH and E2 levels. In ovarian tissues, YLZ improved ovarian morphology, follicle development, and the relative expression of CX43. In vitro studies, we found that YLZ increased the proliferative activity of GCs, ATP levels, glycolytic metabolic rate, HIF1α, CX43, PEK, HK1, LDH mRNA, and protein levels. The study indicated that YLZ increased the proliferation and glycolytic energy metabolism of GCs to improve follicular development further alleviating ovarian function.","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140806046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-26DOI: 10.1186/s13048-024-01416-1
Xin Li, Ting Luan, Yi Wei, JuanJuan Zhang, Chun Zhao, Xiufeng Ling
Polycystic Ovary Syndrome (PCOS) is a common reproductive disorder that frequently affects fertility. The TyG-BMI (Triglyceride glucose-body mass) index is a newly explored parameter that may be linked to reproductive results in individuals with PCOS. Nevertheless, its connection with outcomes in In Vitro Fertilization (IVF) procedures remains uncertain. This study included a total of 966 females who underwent IVF treatments for PCOS. At the baseline, the participants were categorized into four groups according to the quartiles of TyG-BMI measured prior to oocyte retrieval. Subsequently, the study compared the differences in clinical and laboratory outcomes among these four groups. Patients in higher TyG-BMI quartiles exhibited a decreased number of retrieved oocytes, 2PN embryos, and available/high-quality embryos (P < 0.05 for Q1-Q4). Additionally, the multivariable regression analysis revealed that individuals in the top quartile of TyG-BMI had a lower count of accessible embryos (β = -0.224, P = 0.257) and a decreased number of high-quality embryos (β = -0.352, P = 0.028) in comparison to those in the lowest quartile. Nevertheless, there were no notable variances detected in the rates of pregnancy or live births among these quartiles. Furthermore, a linear correlation was noted between the TyG-BMI index and the quantity of accessible embryos (P-non-linear = 0.6, P-overall < 0.001), along with high-quality embryos (P-nonlinear = 0.026, P-overall = 0.006). In contrast, there was no notable linear correlation found between the TyG-BMI index and the available embryo rate (P-nonlinear = 0.60, P-overall = 0.8). The results of this research emphasize the notable correlation between TyG-BMI and IVF results in females diagnosed with PCOS. The interplay of insulin resistance and disorders of lipid metabolism may indeed play a pivotal role in influencing the assisted reproductive outcomes of patients with PCOS. Considering these findings, TyG-BMI proves to be a valuable indicator for exploring this potential association.
{"title":"The association between triglyceride glucose-body Mass Index and in vitro fertilization outcomes in women with polycystic ovary syndrome: a cohort study","authors":"Xin Li, Ting Luan, Yi Wei, JuanJuan Zhang, Chun Zhao, Xiufeng Ling","doi":"10.1186/s13048-024-01416-1","DOIUrl":"https://doi.org/10.1186/s13048-024-01416-1","url":null,"abstract":"Polycystic Ovary Syndrome (PCOS) is a common reproductive disorder that frequently affects fertility. The TyG-BMI (Triglyceride glucose-body mass) index is a newly explored parameter that may be linked to reproductive results in individuals with PCOS. Nevertheless, its connection with outcomes in In Vitro Fertilization (IVF) procedures remains uncertain. This study included a total of 966 females who underwent IVF treatments for PCOS. At the baseline, the participants were categorized into four groups according to the quartiles of TyG-BMI measured prior to oocyte retrieval. Subsequently, the study compared the differences in clinical and laboratory outcomes among these four groups. Patients in higher TyG-BMI quartiles exhibited a decreased number of retrieved oocytes, 2PN embryos, and available/high-quality embryos (P < 0.05 for Q1-Q4). Additionally, the multivariable regression analysis revealed that individuals in the top quartile of TyG-BMI had a lower count of accessible embryos (β = -0.224, P = 0.257) and a decreased number of high-quality embryos (β = -0.352, P = 0.028) in comparison to those in the lowest quartile. Nevertheless, there were no notable variances detected in the rates of pregnancy or live births among these quartiles. Furthermore, a linear correlation was noted between the TyG-BMI index and the quantity of accessible embryos (P-non-linear = 0.6, P-overall < 0.001), along with high-quality embryos (P-nonlinear = 0.026, P-overall = 0.006). In contrast, there was no notable linear correlation found between the TyG-BMI index and the available embryo rate (P-nonlinear = 0.60, P-overall = 0.8). The results of this research emphasize the notable correlation between TyG-BMI and IVF results in females diagnosed with PCOS. The interplay of insulin resistance and disorders of lipid metabolism may indeed play a pivotal role in influencing the assisted reproductive outcomes of patients with PCOS. Considering these findings, TyG-BMI proves to be a valuable indicator for exploring this potential association.","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140805997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}