Journal of Ovarian Research最新文献

{"title":"The gut microbiome and ovarian cysts: a mendelian randomization study.","authors":"Jiahui Qu, Liying Zhang","doi":"10.1186/s13048-025-01767-3","DOIUrl":"10.1186/s13048-025-01767-3","url":null,"abstract":"<p><p>Recent evidence suggests a potential association between gut microbiome and ovarian diseases; however, the causal relationship with ovarian cysts remains unclear. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to investigate potential causal effects between gut microbial genera and ovarian cysts. We used summary statistics from large-scale genome-wide association studies (GWAS) of the gut microbiome and ovarian cysts. After stringent selection of instrumental variables, MR analyses were performed using Inverse variance weighted (IVW) as the primary method, supplemented by Simple mode, MR-Egger, weighted median, and weighted mode approaches. Sensitivity analyses, including Cochran's Q test, MR-Egger regression, MR-PRESSO, and \"leave-one-out\" analysis, were conducted to evaluate the reliability of the results. We identified 17 gut microbial genera with suggestive causal associations with ovarian cysts. Among these, nine genera appeared to be potential risk factors, whereas eight may play a protective role. These findings provide novel insights into microbe-mediated mechanisms and may inform future clinical research on ovarian cysts.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"188"},"PeriodicalIF":4.2,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873645","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":"Improved clinical outcomes with a modified warming protocol in donor oocyte cycles.","authors":"Chun-I Lee, Hsiu-Hui Chen, Shu-Hui Lin, Chun-Chia Huang, Pin-Yao Lin, Tsung-Hsien Lee, Ming-Jer Chen, Maw-Sheng Lee, Chien-Hong Chen","doi":"10.1186/s13048-025-01776-2","DOIUrl":"10.1186/s13048-025-01776-2","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have attempted to improve laboratory efficiency while preserving clinical outcomes by shortening the time to warm cryopreserved embryos, though it is still unclear for oocytes. This study thus aimed to evaluate the effects of a modified warming protocol (MWP) on embryonic development and pregnancy outcomes of vitrified donor oocytes.</p><p><strong>Methods: </strong>The data of this retrospective cohort study were collected from women who underwent donor cycles (fresh or vitrified oocytes) at Lee Women's Hospital, Taiwan, from January 2019 to August 2024. The sample included 13,103 donor oocytes, divided into three groups: conventional warming protocol (CWP) group (n = 8506), MWP group (n = 980), and fresh group (n = 3617).</p><p><strong>Results: </strong>Survival rates after oocyte warming were similar between the CWP and MWP groups (93.7% vs. 93.9%, P > 0.05). Oocyte degeneration rates post-intracytoplasmic sperm injection (ICSI) were similar for vitrified-warmed and fresh oocytes (2.7-3.4% vs. 2.8%). Normal fertilization was lower for vitrified-warmed oocytes (79.5-79.6% vs. 83.0%, P < 0.05), while abnormal fertilization was higher (9.1-10.1% vs. 3.3%). Blastocyst formation and usable blastocyst formation were lower in the CWP group (57.5% and 35.4%) compared to MWP (77.3% and 51.4%) and fresh groups (69.2% and 48.5%). Ongoing pregnancy/live birth was higher in the MWP group than in the CWP group (66.7% vs. 50.4%, P < 0.05). Multivariate analysis showed a positive association between MWP and usable blastocyst formation (adjusted incidence rate ratio = 1.423, 95% CI = 1.268 to 1.597, P < 0.001), as well as ongoing pregnancy/live birth (adjusted odds ratio = 1.899, 95% CI = 1.002 to 3.6, P < 0.05).</p><p><strong>Conclusions: </strong>This study suggests that the MWP enhances the blastocyst formation potential and pregnancy outcomes of vitrified-warmed oocytes, making it similar to that of fresh oocytes. Thus, the MWP may replace the CWP as the standard protocol for optimizing donor cycle outcomes.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"187"},"PeriodicalIF":4.2,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862275","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":"PEDF-Expressing mesenchymal stem cells restore ovarian function via Tim-3-Mediated immune modulation in primary ovarian failure.","authors":"Seyida Yimamuyushan, Song Shi, Aikeremujiang Muheremu, Jinling Yi","doi":"10.1186/s13048-025-01778-0","DOIUrl":"10.1186/s13048-025-01778-0","url":null,"abstract":"<p><strong>Background: </strong>Primary ovarian failure (POF), characterized by premature ovarian dysfunction, remains a therapeutic challenge due to limited interventions addressing its immune dysregulation. Regulatory T cells (Tregs) and immune checkPOFnt pathways, such as Tim-3, are critical yet underexplored targets. Pigment epithelium-derived factor (PEDF), an immunomodulatory protein, offers promise for enhancing mesenchymal stem cell (MSC) therapy in POF.</p><p><strong>Methods: </strong>Using a cyclophosphamide-induced POF mouse model, we evaluated the therapeutic potential of PEDF-overexpressing bone marrow MSCs (BMSCs-PEDF). Mice were stratified into PBS, adenovirus-delivered PEDF (AD-PEDF), control BMSCs (BMSCs-LacZ), and BMSCs-PEDF groups. Outcomes included ovarian index, follicular histology, Treg cell populations, Tim-3/Gal-9 expression, and serum hormone/cytokine profiles.</p><p><strong>Results: </strong>BMSCs-PEDF outperformed other treatments, significantly restoring estrous cyclicity (2.1-fold increase in vaginal exfoliated cells vs. AD-PEDF, P < 0.05) and ovarian index (1.8-fold higher vs. AD-PEDF, P < 0.01). Histology revealed a 3.5-fold increase in viable follicles, with reduced atresia. Mechanistically, BMSCs-PEDF expanded Tim-3 + CD4 + CD25 + Tregs (4.2-fold vs. PBS) and upregulated ovarian Tim-3/Gal-9 expression (3.7-fold vs. AD-PEDF, P < 0.001), correlating with suppressed IFN-γ (62% reduction) and restored estrogen (2.4-fold increase) and progesterone levels.</p><p><strong>Conclusion: </strong>This study demonstrates that PEDF-engineered BMSCs rejuvenate ovarian function by dual mechanisms: enhancing Treg-mediated immune tolerance via the Tim-3/Gal-9 axis and promoting follicular survival. These findings position BMSCs-PEDF as a transformative, mechanism-driven therapy for POF, with broad implications for autoimmune-related infertility.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"182"},"PeriodicalIF":4.2,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855580","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":"Signaling networks and MiRNA crosstalk in ovarian cancer chemoresistance.","authors":"Raksha Nayak, Samyak Pandey, Dileep Kumar, Sachindra Kumar, K Sreedhara Ranganath Pai","doi":"10.1186/s13048-025-01770-8","DOIUrl":"10.1186/s13048-025-01770-8","url":null,"abstract":"<p><p>Epithelial ovarian cancer (EOC), accounting for 90-95% of all ovarian cancer (OC) cases, is the most lethal gynaecological malignancy, primarily due to late-stage diagnosis and the development of chemoresistance. While initial responses to Platinum- and Taxane-based chemotherapy are favorable, nearly 70% of patients relapse within five years. Although signaling pathways such as PI3K/AKT, MAPK, NF-κB, Notch, and Wnt/β-catenin have been individually studied in the context of chemoresistance, recent evidence highlights the importance of dynamic feedback loops and crosstalk among these networks in sustaining the resistant phenotype. Moreover, dysregulated microRNAs (miRNAs), as post-transcriptional regulators, fine-tune these pathways, creating self-sustaining circuits that promote drug efflux, inhibit apoptosis, and maintain cancer stemness. Reciprocal regulation between miRNAs and signaling components establishes robust networks that amplify chemoresistant phenotypes. The review provides a comprehensive overview of the molecular mechanisms driving chemoresistance, emphasising critical elements of signalling pathways and associated miRNAs that contribute to resistance and may function as biomarkers or therapeutic targets to mitigate chemoresistance. To improve clinical outcomes, future research should focus on identifying resistance-associated miRNA signatures and targeting nodal points within miRNA-signaling networks, thereby enabling the development of personalized therapies to overcome drug resistance in EOC.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"185"},"PeriodicalIF":4.2,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855581","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":"Comparison of oral dydrogesterone and vaginal progesterone for luteal phase support in natural and modified natural cycle frozen embryo transfers.","authors":"Yan-Xin Xie, Lin-Lin Jiang, Jia Huang, Lin Li, Qi Qiu, Ping Pan, Yu Li","doi":"10.1186/s13048-025-01765-5","DOIUrl":"10.1186/s13048-025-01765-5","url":null,"abstract":"<p><strong>Background: </strong>This study evaluates the effectiveness of oral dydrogesterone (DYD) for luteal phase support on pregnancy outcomes in patients undergoing frozen embryo transfer with natural cycle protocols (NC-FET), compared with micronized vaginal progesterone (MVP) and combined therapy.</p><p><strong>Methods: </strong>A retrospective study analyzed 2,035 NC-FET cycles, including both natural and modified natural cycles, conducted between January 2019 and August 2022. A total of 2,035 NC-FET cycles were analyzed. Participants were categorized into three groups based on luteal phase support regimens: Group A (699 cycles) received oral DYD, Group B (433 cycles) received MVP, and Group C (903 cycles) received combination therapy. The live birth rates and neonatal outcomes were compared among the groups.</p><p><strong>Results: </strong>The live birth rates were comparable across the groups (43.8%, 39.0%, and 42.1%; P > 0.05). No significant variations were found in clinical pregnancy rate, spontaneous miscarriage rate, ectopic pregnancy rate, premature birth rate, and newborn birth weights. Embryo implantation rates in Groups A and C were significantly higher than in Group B (44.1% and 42.9% vs. 37.8%; P = 0.029). Multi-factor regression analysis identified several independent variables influencing the live birth rate, but luteal support regimens did not significantly impact live birth rates (P > 0.05).</p><p><strong>Conclusion: </strong>In NC-FET cycles, oral DYD demonstrates clinical efficacy comparable to MVP and combined medication. As a monotherapy, oral DYD expands therapeutic options, offering a convenient and effective choice to improve adherence and achieve similar pregnancy outcomes. This finding is significant for guiding clinical practices towards optimal treatment strategies that prioritize patient compliance and satisfaction.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"183"},"PeriodicalIF":4.2,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855578","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":"The mechanism of Ningxin-Tongyu-Zishen formula regulating probdnf/mbdnf balance through PAI-1/tPA signaling pathway in the treatment of premature ovarian insufficiency.","authors":"Jiawen Ma, Chaofan Zhu, Lifang Xie, Shuaiqi An, Zaiyang Zhang, Keying Wang, Yizhou Zhang","doi":"10.1186/s13048-025-01769-1","DOIUrl":"10.1186/s13048-025-01769-1","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian insufficiency (POI) is a refractory gynecological endocrine disorder. Ningxin-Tongyu-Zishen formula (NTZF), developed based on the 'simultaneous heart-kidney regulation' principle, exhibits therapeutic efficacy in treating POI, potentially through regulating proBDNF/mBDNF balance. This study aimed to elucidate the molecular mechanism by which NTZF treats POI via proBDNF/mBDNF modulation.</p><p><strong>Methods: </strong>POI rat models were established using cyclophosphamide (CTX). The therapeutic effects of NTZF were evaluated by analyzing estrous cycles, ovarian indices, follicular development, serum sex hormone levels (FSH, E₂, AMH), and ovarian granulosa cells (OGCs) apoptosis. Following immunofluorescence staining to localize BDNF receptors, proBDNF/mBDNF protein expression was quantified in brain and ovarian tissues. The active metabolite of CTX, phosphoramide mustard (PM), was employed to induce damage in KGN cells. The regulatory effect of NTZF on proBDNF/mBDNF was investigated and compared with recombinant mBDNF protein. tPA and PAI-1 was screened, and their interactions with NTZF were analyzed. mRNA and protein expression of tPA, PAI-1, and tPA-PAI-1 complexes were assessed via q-PCR and Western Blot.</p><p><strong>Results: </strong>NTZF composition was characterized and shown to improve ovarian function in POI rats. Its mechanism involves correcting proBDNF/mBDNF imbalance in both brain and ovarian tissues. NTZF achieved this correction through the PAI-1/tPA signaling pathway, thereby inhibiting apoptosis in damaged KGN cells.</p><p><strong>Conclusion: </strong>Our findings demonstrate that NTZF attenuates PAI-1 expression, diminishes tPA-PAI-1 complex formation, and potentiates tPA-dependent proteolysis of proBDNF into mBDNF, thereby restoring their balance. This restores proBDNF/mBDNF balance, suppresses OGCs apoptosis, and ultimately ameliorates POI.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"184"},"PeriodicalIF":4.2,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855582","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":"Mitochondrial dysfunction in oocytes: implications for fertility and ageing.","authors":"Tong Wang, Peixin Xu, Jianlong Yuan, Hong Chen, Xin Guo, Jing Gao, Yurong Wang, Dongmei Yao, Xin Li, Bingchun Liu, Yang Liu","doi":"10.1186/s13048-025-01764-6","DOIUrl":"10.1186/s13048-025-01764-6","url":null,"abstract":"<p><p>The impact of environmental pollution on fertility has become an essential issue in global public health. Maturation, fertilisation, and embryonic development of oocytes depend on the energy provided by mitochondria; however, with increased environmental pollution and ageing, mitochondrial dysfunction and its subsequent functional and metabolic abnormalities have become leading causes of female fertility decline. When mitochondrial dysfunction occurs in the oocyte, reduced metabolic efficiency leads to impaired nuclear and cytoplasmic maturation of the oocyte, affecting the quality of the oocyte, which further contributes to decreased female fertility and increased risk of infertility, miscarriage, and aneuploid foetuses due to ovarian dysfunction. Several factors affect mitochondrial function, including excess reactive oxygen species (ROS)-induced mutations in mitochondrial DNA (mtDNA), changes in mtDNA copy number, oxidative stress (OS), damage to key cellular components and organelles, and changes in metabolic intermediates and byproducts at the cellular level, further affecting oocyte developmental competence. Mitochondrial dysfunction leads to problems such as abnormal spindle formation and chromosome misalignment, reducing fertilisation potential and embryonic developmental capacity. Mitochondrial dysfunction plays a key role in oocyte ageing and the decline in germ cell function, and an in-depth study of its molecular mechanisms and intervention strategies is highly important for slowing oocyte ageing, increasing fertility, and improving the success rate of assisted reproduction techniques. Clinical trial numberNot applicable.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"186"},"PeriodicalIF":4.2,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855579","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":"Smooth endoplasmic reticulum aggregates in oocytes: a comparison of progestin-primed and GnRH antagonist IVF protocols.","authors":"Hsien-Ming Wu, Cindy Hsuan Weng, Yen-Ju Sung, Le-Tien Hsu, Shang-Yu Huang, Chia-Lin Chang, Hong-Yuan Huang, Yung-Kuei Soong, Liang-Hsuan Chen","doi":"10.1186/s13048-025-01768-2","DOIUrl":"10.1186/s13048-025-01768-2","url":null,"abstract":"<p><strong>Background: </strong>Vitrification improves post-thawed embryo recovery and enables new strategies for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Due to its convenience and efficacy, progestin-primed ovarian stimulation (PPOS) gets more attention in daily practice. However, concerns about the impact of PPOS on oocyte and embryo quality still exist. We aimed to compare the embryological and pregnancy outcomes between PPOS and gonadotropin-releasing hormone (GnRH) antagonist protocol in IVF/ICSI cases.</p><p><strong>Methods: </strong>This was a retrospective cohort study of 545 women undergoing IVF/ICSI cycles from July 2017 to December 2018. The patients were allocated into two groups: the PPOS and GnRH antagonist group, based on 1:1 propensity score matching. In both groups, all viable embryos were cryopreserved for later transfer. The primary endpoint was the prevalence of smooth endoplasmic reticulum aggregates (SERa) in oocytes. Secondary outcomes included the cycle characteristics and pregnancy outcomes.</p><p><strong>Results: </strong>Ovarian stimulation duration and serum estradiol level on trigger day were significantly higher in the PPOS group compared to the GnRH antagonist group. The prevalence of SERa + cycles was 9.4% in our cohort (13.0% and 12.2% in the PPOS and GnRH antagonist groups, respectively, p = 0.221). There were more frozen embryos (5.3 ± 4.5 vs. 4.8 ± 4.0, p = 0.378) in the PPOS group than in the GnRH group, particularly for the subgroup of low responders (1.6 ± 1.2 vs. 1.2 ± 1.0, p = 0.043). No significant differences were observed between the groups regarding clinical pregnancy rate, miscarriage, live birth rate, and cumulative live birth rate in the following two years after oocyte retrieval.</p><p><strong>Conclusions: </strong>Our findings suggest that the PPOS protocol provides clinical benefits and safety with comparable oocyte quality and pregnancy outcomes to the GnRH antagonist protocol.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"181"},"PeriodicalIF":4.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835358","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":"Oleic acid activates TGFβ-Smad3 signaling to promote ovarian cancer progression.","authors":"Zhengyang Guo, Yinjia Li, Yunyun Guo, Aosong Zhang, Xiao Huo, Ying Song, Bing Li, Yuanjun Tang, Tianhui He, Tong Liu, Lixiang Xue, Yi Qu, Jiagui Song","doi":"10.1186/s13048-025-01763-7","DOIUrl":"10.1186/s13048-025-01763-7","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer represents the most aggressive and lethal gynecological cancer, frequently demonstrating a distinct propensity for abdominal metastasis. Malignant ascites caused by abdominal metastasis provide a tumor microenvironment (TME) in ovarian cancer. Notably, oleic acid is abundant in ovarian cancer ascites, though its functional significance in TME modulation and tumor metastatic regulation remains poorly characterized. Stearoyl-CoA desaturase 1 (SCD1) is the key enzyme in the synthesis of oleic acid. Our study systematically explores the pathological role of oleic acid and evaluates the therapeutic effects of SCD1 inhibitor in ovarian cancer progression.</p><p><strong>Results: </strong>Oleic acid treatment significantly enhanced proliferation of ovarian cancer cells and patient-derived organoids. Remarkably, oleic acid also increased membrane fluidity and promoted cell migration. Mechanistically, TGFβ-Smad3 signaling cascade is selectively activated by oleic acid, and inhibited by SCD1 suppression. Importantly, activation of Smad3 caused by oleic acid treatment triggered epithelial-mesenchymal transition of ovarian cancer cells. Clinical relevance was established that SCD1 expression was positively correlated with the activity of Smad3 in ovarian cancer tissues. Finally, in vivo studies showed that SCD1 inhibitor treatment suppressed tumor progression during intraperitoneal dissemination.</p><p><strong>Conclusion: </strong>This study provides novel insights into the supporting role of oleic acid in fueling tumor proliferation and metastasis, mechanistically associated with its specific activation of TGFβ-Smad3 signaling. Therapeutically, pharmacological targeting oleic acid synthesis by SCD1 inhibitor emerges as a promising strategy for precision oncology in ovarian cancer management.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"180"},"PeriodicalIF":4.2,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821637","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":"MYB/AKT3 axis is a key driver of ovarian cancer growth, aggressiveness, and chemoresistance.","authors":"Kunwar Somesh Vikramdeo, Orlandric Miree, Shashi Anand, Amod Sharma, Sanjeev Kumar Srivastava, Seema Singh, Rodney P Rocconi, Ajay Pratap Singh","doi":"10.1186/s13048-025-01761-9","DOIUrl":"10.1186/s13048-025-01761-9","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) remains the most lethal gynecologic malignancy in the United States due to its late diagnosis, aggressive nature, and poor responsiveness to existing therapies. Dissecting the molecular mechanisms and identifying molecular drivers of aggressiveness and therapy resistance is critical for devising new therapies and improving patient outcomes.</p><p><strong>Methods: </strong>MYB expression was evaluated in a panel of OC cell lines by immunoblotting. Gain and loss of function studies were performed by developing stable control and forced-MYB-expressing and -silenced cell lines, respectively. Functional assays included growth kinetics, clonogenicity, cell cycle, live-dead cell measurements, and annexin-V staining, followed by flow cytometry, migration and invasion assays, and MTT assays following drug treatment. Gene expression profiling was done using the nanoString PanCancer Progression panel. Chromatin immunoprecipitation (ChIP) was performed to confirm MYB binding to the responsive gene promoter, followed by siRNA-mediated silencing to establish the intermediary role in potentiating the downstream effects.</p><p><strong>Results: </strong>Low to high MYB expression was reported in all OC cell lines, with negligible expression reported in normal ovarian surface epithelial cells. MYB expression was significantly higher in aggressive (SKOV3-ip) and chemoresistant (A2780-CP) OC cell lines compared to the parental (SKOV3 and A2780) cells. Functional assays in MYB-overexpressing and -silenced OC cell lines demonstrated a role of MYB overexpression in increased cell proliferation, survival, migration, invasion, EMT, and chemoresistance. nanoString analysis and comparison of transcriptomic data of MYB-silenced SKOV3-ip and MYB-overexpressing SKOV3 cells with their respective control cells identified MYB-dependent genes. Interestingly, these target genes showed a limited overlap between cell lines, suggesting a cell-specific MYB-regulated gene regulation. AKT3 was consistently identified as a common MYB-regulated gene in multiple OC cell lines and confirmed as a direct transcriptional MYB target through confirmation of MYB binding to its promoter. Pathway analysis using the MYB-regulated transcriptomic data also identified PI3K/Akt signaling to be activated in MYB-overexpressing cells. siRNA-mediated silencing of AKT3 confirmed its role in potentiating the oncogenic actions of MYB in OC cells.</p><p><strong>Conclusion: </strong>MYB/AKT3 axis drives ovarian cancer growth, aggressiveness, and chemoresistance, highlighting its potential as a therapeutic target in ovarian cancer.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"179"},"PeriodicalIF":4.2,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821636","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}