Journal of Ovarian Research最新文献

{"title":"Luteinizing hormone change trajectories in gonadotropin-releasing hormone antagonist protocols are associated with assisted reproductive outcomes: results from a retrospective cohort study.","authors":"Xun Su, Qi Zheng, Dongyang Zhang, Qian Li, Hua Zhang, Yiqing Fan, Tao Yin, Weiwei Zou, Lei Zhang, Jie Zhang, Zhaolian Wei, Yunxia Cao, Chunmei Liang, Dongmei Ji","doi":"10.1186/s13048-026-02140-8","DOIUrl":"10.1186/s13048-026-02140-8","url":null,"abstract":"<p><strong>Context: </strong>Luteinizing hormone (LH) plays an integral role in follicular development. In gonadotropin-releasing hormone (GnRH) antagonist protocols, LH levels have been demonstrated to affect assisted reproductive technology (ART) outcomes. However, the exact nature of this relationship remains unclear, and LH measurements at a single time point may not be sufficient to capture it fully.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study on 4,953 infertile women who underwent their first ART cycle with the GnRH antagonist protocol. Four LH measurements (basal status, antagonist administration day and 24 h later, and ovulation trigger day) were obtain for all participants. We used group-based trajectory modeling (GBTM) to characterize the trajectories of LH level changes during antagonist protocol implementation. Factors influencing the different LH trajectories were explored. Associations between LH levels at different time points and their trajectories with the number of obtained oocytes and ART outcomes in embryo transfer (ET) cycles were analyzed.</p><p><strong>Results: </strong>Based on the statistical criteria, the model with 4 trajectories were selected as the best-fitting model, and the LH change trajectories during antagonist protocol can be grouped into stable (77.0%), rising (11.0%), decreasing (6.2%) and fluctuating (5.8%) types. Different trajectory groups exhibited significant differences in the number of retrieved oocytes. Compared with that in the stable trajectory group, the oocyte yield in the rising trajectory group decreased and that in the fluctuating trajectory group increased. Of these participants, 884 underwent fresh ET cycles, with no significant differences in pregnancy outcomes between the different trajectory groups. On ovulation trigger day, high LH levels predicted better pregnancy outcomes, indicating significant positive associations with the odds of biochemical pregnancy, clinical pregnancy and live birth.</p><p><strong>Conclusion: </strong>Oocyte yield differed significantly among the LH trajectory groups, suggesting that LH dynamics during antagonist controlled ovarian stimulation may be relevant to treatment outcomes. For individuals with risk factors for a rising trajectory (e.g., advanced age, higher body mass index), closer monitoring of LH profiles may be warranted. For fresh ET cycles, trigger-day LH levels may merit heightened clinical attention.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005589","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":"Two compound heterozygous MEIOSIN (likely) pathogenic variants cause female infertility with premature ovarian insufficiency through the disruption of meiosis-related gene transcription.","authors":"Xuan Sha, Yan Zhang, Xun Xia, Haitian Ding, Yuqian Li, Guotong Li, Rong Hua, Kuokuo Li, Rui Guo, Danli Du, Yuping Xu, Yunxia Cao, Huan Wu, Yingchun Liu","doi":"10.1186/s13048-026-02129-3","DOIUrl":"10.1186/s13048-026-02129-3","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian insufficiency (POI) is a major contributor to female infertility; however, its genetic basis remains insufficiently understood. MEIOSIN is crucial for initiating meiosis by activating a subset of key meiotic genes that regulate the transition from mitosis to meiosis in mammalian germ cells. Recent studies suggest that biallelic MEIOSIN variant may contribute to POI in humans, yet further analysis is required to confirm and clarify this role.</p><p><strong>Methods: </strong>To identify potential pathogenic variants associated with POI, whole-exome sequencing was conducted in the affected individuals, followed by Sanger sequencing for variant validation. To evaluate the functional consequences of these variants, a series of in vitro assays was performed, including Western blotting, immunostaining, and structural modeling of mutant proteins. Additionally, a dual-luciferase reporter assay was utilized to assess whether the identified variants influenced the transcriptional activity of MEIOSIN.</p><p><strong>Results: </strong>Two compound heterozygous variants in MEIOSIN-c.980T > C (p.Leu327Pro) and c.1068_1092del (p.His356fs*14)-were identified in two affected sisters, with the latter representing a novel variant. Sanger sequencing confirmed that the two variants were inherited from each parent, thereby establishing compound heterozygosity. Functional characterization revealed that the frameshift variant resulted in a truncated MEIOSIN protein with aberrant intracellular localization. While the missense variant did not impact MEIOSIN expression or localization, it disrupted the protein's 3D structure. Furthermore, dual-luciferase assays demonstrated that both variants impaired MEIOSIN's transcriptional regulation of downstream meiotic genes. According to the ACMG/AMP guidelines, the frameshift variant was classified as pathogenic, while the missense variant was classified as likely pathogenic.</p><p><strong>Conclusion: </strong>These findings provide compelling evidence that pathogenic biallelic variants in MEIOSIN represent a recurrent genetic cause of POI in humans.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13377809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005558","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":"Impact of salpingectomy on ovarian response to hormonal stimulation in in vitro fertilization (IVF) cycles.","authors":"Yohan Benchimol, Stéphane Sanchez, Catherine Racowsky, Rossana Cicinelli, Achraf Benammar, Jean-Marc Ayoubi","doi":"10.1186/s13048-026-02114-w","DOIUrl":"10.1186/s13048-026-02114-w","url":null,"abstract":"<p><strong>Background: </strong>The coagulation-section of the mesosalpinx during the salpingectomy can lead to injuries on the ovarian vascularization, and thus to the ovarian response to hormonal stimulation. Does salpingectomy affect negatively the follicles recruitment in in vitro fertilization (IVF) cycles? We conducted a monocentric retrospective case-control study including all patients undergoing IVF cycle with a history of unilateral salpingectomy for hydrosalpinx (HSX) or ectopic pregnancy (EP) (Group S), and each of them was matched to two controls (Group C) treated in the same month, according to their: age, AMH level, and BMI. The difference in follicle recruitment the day of trigger between the two ovaries of each patient was calculated. The primary endpoint was the difference between the two groups in the total number of follicles with a diameter ≥ 13 mm. Secondary endpoints were the difference between groups regarding the number of (1) mature follicles (diameter ≥ 16 mm) and intermediate follicles [13.0-15.5 mm]; (2) cycle cancellation rate; and (3) total number of oocytes and mature oocytes retrieved. The same comparisons were also carried out on subgroups according to the indication for salpingectomy (HSX or EP).</p><p><strong>Results: </strong>114 and 228 patients were included in Groups S and C, respectively. Compared to Group C, Group S patients showed a greater difference between ovaries in the total number of follicles recruited (0.76 ± 3.95 vs. -0.18 ± 3.37, p = 0.002) and in the number of mature follicles (0.51 ± 2.91 vs. -0.14 ± 2.85, p = 0.05). No significant differences were observed for the number of intermediate follicles, or the total number of oocytes or mature oocytes retrieved. However, the cycle cancellation rate was significantly higher in Group S (13.2% vs. 3.1%, p < 0.001). Subgroup analysis revealed no significant differences between each of the Group S subgroups (HSX and EP) regarding follicular recruitment. Nevertheless, both subgroups had significantly more cancelled cycles compared with their respective controls (HSX: 12.5% vs. 4.4%, p < 0.001; EP: 8.8% vs. 1.8%, p = 0.004).</p><p><strong>Conclusion: </strong>Salpingectomy has a negative impact on follicles recruitement in IVF cycles. This risk must be taken into consideration when scheduling this surgery.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005493","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":"Dissecting the transcriptomic signature of porcine oocyte during primordial follicle formation from single cell resolution.","authors":"Xin-Hao Zhang, Kai Zhang, Yu Tian, Gui-Li Ruan, Fa-Li Zhang, Ke-Xin Zhu, Ai-Ying Li, Wei Shen, Jun-Jie Wang","doi":"10.1186/s13048-026-02126-6","DOIUrl":"10.1186/s13048-026-02126-6","url":null,"abstract":"<p><strong>Background: </strong>Ovarian reserve, refers to the number of primordial follicle (PF) in mammals, is a decisive factor affecting the reproductive lifespan of females. However, the molecular mechanism of PF formation has not been fully elucidated, especially in large mammals. In the study, the ovarian tissues at embryonic day 95 (E95) and postnatal day 0 (PD0) were collected for single-nucleus transcriptome sequencing, attempting to investigate the transcriptome dynamic of porcine oocyte during PF formation at a single-cell level.</p><p><strong>Results: </strong>In the results, we identified in detail three germ cell clusters with different transcriptional modes. Moreover, through a comparative analysis of developmental trajectory in pig, mouse and monkey, several conserved regulatory genes that associated with the developmental fate of germ cells were identified. By employing SCENIC software, we identified 27 transcription factors specific to developmental stages of germ cells. In addition, a protein interaction network between transcription factors and conserved genes was constructed and it discovered a key transcription factor, enhancer of zeste homolog 2 (EZH2), which is expressed exclusively in oocytes during PF formation, and there is the asynchrony of its expression in germ cells between the medulla and cortex regions. Further, during the in vitro culture of mouse ovaries, the inhibition of EZH2 expression significantly decreased the number of oocytes and leading to the decline of protein expressions that essential for PF formation.</p><p><strong>Conclusions: </strong>This study provides a single-cell map of pig ovary in the late embryonic development and newly born periods, and enriches the public understanding of primordial follicle formation in mammals.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13466142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982178","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":"Oncofertility outcomes after fertility-sparing surgery for borderline ovarian tumors: results of a large retrospective study.","authors":"Rongmin Wang, Yinping Xiao, Taniya Fernando, Yanli Chen, Xiaoyong Zhu","doi":"10.1186/s13048-026-02142-6","DOIUrl":"10.1186/s13048-026-02142-6","url":null,"abstract":"<p><strong>Background: </strong>Fertility-sparing surgery (FSS) is a key therapeutic strategy for borderline ovarian tumors (BOTs) in young women. However, the optimal surgical approaches and the prognostic significance of clinicopathological features remain a subject of debate. This study aimed to evaluate the oncological safety and reproductive outcomes following FSS in a large cohort of young BOT patients.</p><p><strong>Methods: </strong>We retrospectively reviewed 533 patients (aged 20-40 years) diagnosed with BOTs who underwent FSS at a single academic medical center between 2010 and 2021. Survival outcomes were estimated using the Kaplan-Meier method. To identify independent prognostic factors for recurrence, variable selection was performed using the Least Absolute Shrinkage and Selection Operator regression, followed by multivariable Cox proportional hazards analysis with backward elimination.</p><p><strong>Results: </strong>Over a median follow-up of 61.90 months (range: 1.03-176.53months), 85 (15.95%) patients experienced recurrence, comprising 77 (14.45%) borderline recurrences and 8 (1.50%) invasive transformation. The 5-year and 10-year disease-free survival rates were 82.0% and 75.9%, respectively. Multivariable analysis identified bilateral ovarian lesions (HR 2.07, p = 0.017), exophytic growth (HR 3.66, p < 0.001), intraepithelial carcinoma (HR 4.23, p = 0.004), and FIGO stage III (HR 2.23, p = 0.014) as independent prognostic risk factors for recurrence. Notably, peritoneal biopsy was associated with a significantly lower recurrence risk (HR 0.42, p = 0.004). Histological stratification revealed that for serous BOTs, exophytic growth (HR 4.05, p < 0.001), cystectomy (HR 3.03, p = 0.008), FIGO stage III (HR 2.46, p = 0.011) were risk factors, while peritoneal biopsy (HR 0.44, p = 0.018) remained protective. For MBOT, intraoperative chromotubation was identified as a risk factor (HR 8.62, p < 0.001). Among 176 patients attempting conception, the live birth rate was 70.45%. In those utilizing assisted reproductive technology (n = 31), the pregnancy and live birth rates were 77.42% and 48.39%, respectively.</p><p><strong>Conclusions: </strong>FSS is oncologically safe and offers favorable reproductive outcomes for young women with BOTs. The identified prognostic factors were instrumental in tailoring individualized surveillance and management strategies.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987982","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":"Calcitriol is involved in maintaining primordial follicle reserve through the inhibition of the PI3K/Akt signaling pathway.","authors":"Shuang Liu, Ye Chen, Hongwei Wei, Huiyu Liu, Weiyong Wang, Yanli Sun, Luchun Zhang, Sihui He, Xiaodan Zhang, Jingjie Li, Meijia Zhang","doi":"10.1186/s13048-026-02135-5","DOIUrl":"10.1186/s13048-026-02135-5","url":null,"abstract":"<p><strong>Background: </strong>In mammals, precise regulation of primordial follicle activation is essential for maintaining the female reproductive lifespan. In this study, we demonstrated that the vitamin D receptor (VDR) is expressed in both pre-granulosa cells and oocytes within primordial follicles of mice and humans.</p><p><strong>Methods: </strong>The VDR ligand, calcitriol, was tested through ovarian culture and intraperitoneal injection experiments in neonatal mice. In addition, oral administration of the calcitriol precursor VD3 was performed in mice. Calcitriol was also tested on cultured human ovarian fragments.</p><p><strong>Results: </strong>Calcitriol inhibited the activation of primordial follicles in neonatal mice. Moreover, calcitriol promoted the formation of the VDR-RXR-p85α complex, thereby stabilizing the PI3K heterodimer (p85α/p110) and inhibiting activation of the PI3K/Akt signaling pathway. This resulted in reduced phosphorylation of FOXO3a in the ovaries and decreased nuclear export in oocytes of primordial follicles, thereby suppressing the activation of primordial follicles. Oral administration of VD3 significantly decreased the number of growing follicles and prolonged the reproductive age in mice compared with controls. Importantly, calcitriol also inhibited human primordial follicle activation and reduced p-Akt levels in cultured ovarian fragments.</p><p><strong>Conclusion: </strong>Thus, calcitriol inhibits the activation of both mouse and human primordial follicles by suppressing the VDR-mediated PI3K/Akt signaling pathway. As an oral medication, the calcitriol precursor VD3 may be used to maintain the primordial follicle reserve and extend the reproductive age in women.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147987980","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":"Ubiquitin-specific proteases in ovarian cancer: molecular mechanisms and therapeutic implications.","authors":"Lu Deng, Yuzhao Jiang, Danning Wang, Jing Yu, Lingying Wu","doi":"10.1186/s13048-026-02138-2","DOIUrl":"10.1186/s13048-026-02138-2","url":null,"abstract":"<p><p>Ovarian cancer (OC) remains one of the most lethal gynecological malignancies, largely due to late-stage diagnosis, frequent recurrence, and the development of resistance to standard therapies. These clinical challenges highlight the urgent need for a deeper understanding of the biological processes driving OC and the identification of novel therapeutic targets. The ubiquitin-proteasome system is a central mechanism for selective protein degradation. Accumulating evidence indicates that deubiquitinases, particularly ubiquitin-specific proteases (USPs), are key regulators of oncogenic signaling and therapy response in OC. This review provides a comprehensive overview of how dysregulated USPs shape major cancer hallmarks in OC, including cell-cycle control, DNA damage repair and genomic stability, apoptosis, metastasis, metabolic reprogramming, and immune evasion. We further summarize advances in developing USP-directed pharmacologic inhibitors, discuss emerging translational strategies, and evaluate the rationale for combining USP inhibition with established treatments such as platinum-based chemotherapy and poly-ADP ribose polymerase inhibitors (PARPis) to overcome resistance. Collectively, understanding USP-dependent networks may facilitate the identification of novel biomarkers and therapeutic targets, offering new strategies for precision treatment in OC.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13362014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147973284","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":"Ovarian tissue oocyte-in vitro maturation combined with ovarian tissue cryopreservation: a promising urgent fertility preservation strategy for hematological patients before HSCT.","authors":"Yingqiao Ding, Tiantian Su, Yanling Wan, Yanru Hou, Yuan Fan, Fang Fang, Peng Zuo, Xiaowei Li, Shengnan Duan, Nannan Huang, Jianliu Wang, Lanping Xu, Rong Liang, Li Tian","doi":"10.1186/s13048-026-02136-4","DOIUrl":"10.1186/s13048-026-02136-4","url":null,"abstract":"<p><strong>Background: </strong>Hematological diseases to be treated with HSCT are a definite indication for fertility preservation (FP). Ovarian tissue oocyte in vitro maturation (OTO-IVM) combined with ovarian tissue cryopreservation (OTC) may be a promising and urgent FP strategy for this population. This study aims to evaluate the efficacy of OTO-IVM for this population and identify which hematological diseases are more likely to benefit from OTO-IVM.</p><p><strong>Methods: </strong>This study included 44 hematological patients before HSCT who underwent the OTO-IVM combined with OTC for urgent FP. Patients were divided into the malignant hematological disease (MHD) and non-MHD groups and the OTO-IVM outcomes were retrospectively analysed. Donated ovarian tissues from MHD, non-MHD and control group were subjected to further molecular and pathological study.</p><p><strong>Results: </strong>Patients with non-MHD exhibited significantly higher serum anti-Müllerian hormone (AMH) levels (4.36 ± 3.14 vs. 2.08 ± 1.57, p = 0.017) and a greater number of retrieved immature oocytes (10.58 ± 7.54 vs. 4.85 ± 3.26, p = 0.012) than those with MHD. Although the maturation rate showed a non-significant decreasing trend in the non-MHD group (35.80 ± 28.12 vs. 49.83 ± 33.96, p = 0.163), multivariable analysis demonstrated that non-MHD was associated with a lower per-patient IVM rate. The final number of MII oocytes did not differ significantly between groups (3.58 ± 4.07 vs. 2.23 ± 2.01, p = 0.264). Notably, increased apoptosis of ovarian stromal cells may contribute to impaired oocyte maturation competence in patients with aplastic anemia (AA). Consistently, AA ovarian tissues displayed activation of apoptotic signalling pathways and dysregulated T cell activation-associated gene expression compared with MHD and impaired oocyte development and maturation compared with control group.</p><p><strong>Conclusions: </strong>OTO-IVM combined with OTC appears feasible for urgent fertility preservation in hematological patients prior to HSCT. Our exploratory findings suggest that ovarian stromal cell apoptosis may contribute to reduced oocyte maturation competence in AA, which warrants further validation and optimization of maturation rates.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147973203","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":"Progress of estrogen receptor and splice variants in ovarian carcinoma.","authors":"Ting Mo, Ziqi Hong, Youqiong Mo, Jing Tian, Jian Chen","doi":"10.1186/s13048-026-02122-w","DOIUrl":"10.1186/s13048-026-02122-w","url":null,"abstract":"<p><p>Ovarian cancer is a typical estrogen-dependent tumor, with its initiation and progression closely associated with estrogen regulation. Estrogen exerts physiological effects by binding to estrogen receptors (ERs), and aberrant activation of ER signaling pathways is a crucial mechanism in the pathogenesis of ovarian cancer. ERα promotes ovarian cancer cell proliferation and migration, and is linked to cisplatin resistance, while its splice variants modulate cancer cell sensitivity to tamoxifen. Conversely, ERβ functions as a tumor suppressor and counteracts the pro-tumorigenic effects of ERα. Distinct ERβ subtypes have divergent biological functions, and their agonists can enhance cancer cell chemosensitivity. G protein-coupled estrogen receptor 1 (GPER1), a membrane estrogen receptor, mediates the non-genomic effects of estrogen. Its role depends on clinical stages and subcellular localization, and its association with ovarian cancer prognosis is under debate. GPER1 may interact with ERα in ovarian cancer, yet the specific crosstalk mechanism remains unelucidated. Elucidating the complex functional crosstalk of estrogen and ERs, as well as the diverse roles of ER splice variants, is expected to provide novel insights for the early diagnosis and identification of therapeutic targets for ovarian cancer.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13339317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147930567","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":"Hyperhomocysteinemia reduces the high-quality embryo rate in PCOS patients undergoing IVF/ICSI: clinical evidence and a preliminary exploration of mechanisms in KGN cells.","authors":"Haofei Shen, Tianyu Jia, Xiaorong Luo, Jianxiu Zheng, Chunjie Zhang, Shan Gao, Xuehong Zhang, Junjun Huang","doi":"10.1186/s13048-026-02120-y","DOIUrl":"10.1186/s13048-026-02120-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Homocysteine (Hcy) is a sulfur-containing intermediate metabolite during methionine metabolism. Studies indicate that individuals with polycystic ovary syndrome (PCOS) have higher circulating Hcy levels relative to unaffected populations. Hyperhomocysteinemia (HHcy) has been implicated in multisystem cytotoxicity. This study was designed to evaluate the association between Hcy levels and embryo quality and pregnancy outcomes in PCOS patients undergoing assisted reproductive technologies (ART). Mechanistic insights were explored through in vitro assays and combined network pharmacology analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 599 patients with PCOS who were undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) were retrospectively analyzed. Patients were stratified into three groups based on Hcy levels (low, intermediate, and high). Comparative analyses of clinical and laboratory parameters were performed across strata. Multivariable logistic regression models were developed to evaluate the independent association between Hcy levels and reproductive outcomes after adjustment for potential confounders. In vitro assays were conducted using KGN cells, a human granulosa-like tumor-derived cell line. Cellular viability after exposure to graded concentrations of Hcy was quantified using the Cell Counting Kit-8 (CCK-8) assay, while cell apoptosis was observed via flow cytometry. For systems-level analysis, Hcy-associated targets were retrieved from SwissTargetPrediction, TargetNet, BATMAN-TCM, and PharmMapper databases. PCOS-related targets were curated from OMIM, GeneCards, DrugBank, and DisGeNET repositories. Overlapping targets were analyzed for protein-protein interaction (PPI) network construction using the STRING platform, followed by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Comparative univariate analysis showed a significant difference in the high-quality embryos among the three Hcy strata, whereas other clinical parameters did not reach statistical significance. Multivariable regression analysis identified a robust inverse association between Hcy level and high-quality embryo rate (β = -1.04, 95% CI: -1.36 to -0.72; p &lt; 0.0001), which remained stable after adjustment for confounding variables, including creatinine clearance rate (β = -1.06, 95% CI: -1.40 to -0.72; p &lt; 0.0001). In vitro results showed that exposure to Hcy (80-160 µM, 24 h) significantly reduced KGN cell viability and increased apoptotic rates in a concentration-dependent manner. Network pharmacology analysis identified 102 intersecting targets that may mediate Hcy-associated effects in PCOS. KEGG pathway enrichment revealed significant involvement in lipid metabolism and atherosclerosis, viral infections (i.e., hepatitis B and cytomegalovirus), the AGE-RAGE signaling pathways in diabetic complications, and the TNF","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13339867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147930522","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}