Journal of Ovarian Research最新文献

Background: Ovarian cancer is a widely prevalent gynecological malignancy associated with significant morbidity and mortality. Scutellaria barbata D. Don (SB), a traditional Chinese medicine, has been reported to have diverse biological effects, including anti-ovarian cancer effects. However, the specific effects and underlying mechanism of the alkaloid fraction, the active fraction isolated from SB, in ovarian cancer remain unclear. This study aimed to explore the anti-tumor effects and underlying mechanisms of the alkaloid fraction of Scutellaria barbata D. Don (SBA) in ovarian cancer.

Methods: SBA was extracted by alcohol solvent extraction, and its chemical composition was analyzed using chromogenic reaction and high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC/Q-TOF-MS). The effects of SBA on the proliferation, migration and apoptosis of human ovarian cancer cells (SKOV3) were detected by CCK-8 assay, clone formation assay, scratch assay, transwell assay, flow cytometry, Hoechst 33,342 staining and Western blot. SKOV3 xenograft nude mouse model was established to further investigate the in vivo effects of SBA. Serum and tissue samples were collected for molecular-biological indicators, and pathological changes were evaluated by hematoxylin-eosin, immunohistochemistry, and Western blot.

Results: A total of 38 nitrogen-containing compounds were detected in SBA. SBA inhibited the proliferation and migration of SKOV3 cells in a dose-dependent manner, in addition to inducing significant cell apoptosis. In the SKOV3 xenograft model, SBA attenuated ovarian cancer tumor growth with no significant organ toxicity. The anti-tumor effects of SBA were associated with downregulation of Bcl-2, N-cadherin, MMP2, MMP9, and upregulation of Bax, cleaved caspase-3/ caspase-3, cleaved caspase-9, E-cadherin, P-p38/ p38, and P-p53/ p53 both in vitro and in vivo. Additionally, SBA exhibited synergy with cisplatin (DDP) and alleviated cisplatin-induced renal damage.

Conclusion: SBA suppresses ovarian cancer by triggering apoptosis and inhibiting cell migration via the p38-p53 pathway. Combining SBA with DDP reduces drug toxicity and potentiates the anti-tumor effects. Therefore, SBA is a promising candidate for treating ovarian cancer, and mitigating the toxic side effects of DDP in ovarian cancer.

Background: The clinical implications of elevated luteinizing hormone (LH) levels in patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) fresh embryo transfer cycles remain unclear, particularly regarding oocyte maturation and pregnancy outcomes. We aimed to evaluate the impact of basal LH elevation on treatment outcomes and compare the efficacy of protocols involving gonadotropin-releasing hormone antagonist (GnRH-ant) and gonadotropin-releasing hormone agonist (GnRH-a) for ovarian stimulation in patients with PCOS undergoing in vivo IVF/ICSI.

Methods: This single-center, retrospective cohort study included 1,269 patients with PCOS who underwent IVF/ICSI treatment following a flexible GnRH-ant or long GnRH-a protocol with a human chorionic gonadotropin trigger between January 2013 and December 2023. Primary outcomes included the number of retrieved oocytes, metaphase II (MII) oocytes, two pronuclear embryos, high-quality embryos, and the ovarian hyperstimulation syndrome (OHSS) rate. Secondary outcomes included clinical pregnancy, miscarriage, and live birth rates following fresh embryo transfer.

Results: Among the participants, 492 (38.77%) exhibited basal LH levels of ≥ 10 mIU/mL, and 777 (61.23%) had LH levels of < 10 mIU/mL. Additionally, 465 (36.64%) and 804 (63.36%) participants underwent GnRH-ant and GnRH-a protocols, respectively. Elevated basal LH levels showed no significant associations with MII oocyte yield, fertilization rate, high-quality embryo count, or clinical pregnancy outcomes (all p > 0.05). However, patients with high LH levels demonstrated increased oocyte retrieval (p = 0.008), a high incidence of ovarian hyperstimulation syndrome (OHSS) (p < 0.001), and reduced fresh embryo transfer rates (p = 0.003). The GnRH-ant protocol required shorter stimulation duration (p < 0.001) and lower amounts of recombinant follicle-stimulating hormone (p < 0.001) than did the GnRH-a protocol. The GnRH-ant protocol also yielded significantly higher proportions of oocytes (p = 0.022), MII oocytes (p = 0.003), and high-quality embryos (p < 0.001); however, it exhibited lower fresh embryo transfer rates (p < 0.001). The two protocols showed no significant differences concerning clinical pregnancy success or OHSS risk.

Conclusions: Elevated basal LH levels did not impair the outcome of fresh embryo transfer in women with PCOS undergoing IVF/ICSI. However, the number of retrieved oocytes and the OHSS rate were significantly higher in patients with high basal LH levels. The GnRH-ant protocol is an efficient alternative for this subpopulation, particularly regarding stimulation efficiency.

Clinical trial number: Not applicable.

Background: Biallelic variants in meiosis inhibitor protein 1 (MEI1) have recently been implicated in embryonic developmental arrest. However, the genomic and transcriptomic consequences of these MEI1 variants remain only partially understood. This study aims to expand the known MEI1 variant spectrum and elucidate the molecular mechanisms by which these variants affect early embryonic development.

Results: Two unrelated infertile women experiencing embryonic developmental arrest were identified to carry novel biallelic MEI1 variants using whole-exome sequencing. The functional impact of these variants was characterized through a combination of in vivo and in vitro analyses. Additionally, genomic and transcriptomic sequencing was performed on embryos from one of the patients. Patient 1 carried compound heterozygous variants c.622T > C (p.Ser208Pro) and c.2647 C > T (p.Arg883Ter), while Patient 2 harbored c.3037T > G (p.Trp1013Gly) and c.2546_3525del (EX21-31del) variants. Genomic analysis of embryos demonstrated extensive chromosomal abnormalities and maternal triploidy, indicating a compromise in meiotic integrity due to biallelic MEI1 variants. Transcriptomic profiling revealed downregulation of meiotic cell cycle genes. Additionally, downregulation of epigenetic regulatory genes, particularly those involved in histone demethylation and deacetylation, was observed, suggesting abnormal transcriptional activation and genomic instability.

Conclusions: Our findings broaden the spectrum of MEI1 variants associated with embryonic developmental arrest and highlight the essential role of MEI1 in oocyte meiosis and early embryonic chromosomal stability.

Background: Ovarian tissue cryopreservation followed by transplantation after cancer remission is a fertility preservation strategy available for certain patient groups, such as pre-pubertal and adolescent girls, as well as adult females requiring urgent gonadotoxic therapy. Quantitative assessment of follicular density in cryopreserved cortical tissue is critical for evaluating tissue quality and estimating its reproductive potential. Conventional analysis, based on manual follicle counts in serial histological sections, is time-consuming, labor-intensive, and prone to variability from uneven follicle distribution and inconsistent tissue orientation. To address these limitations, we developed a high-throughput, automated method combining micro-CT, machine learning, and morphological analysis to quantify oocyte density and other morphological features throughout entire ovarian cortical tissue samples.

Results: Three-dimensional segmentation analysis enabled quantification of oocyte density in the samples within the cortical region 1 mm below the surface epithelium. Oocytes in pediatric samples were located significantly closer to the surface compared to those in adult tissue, with median distances of 139.4 μm and 370.2 μm, respectively (P < 0.0001) and exhibited markedly higher local oocyte neighbor counts, with median values of 6 and 2 in pediatric and adult tissues, respectively (P < 0.0001), consistent with higher oocyte density and clustered spatial organization in younger individuals. Simulated histology using every 10th virtual sections -corresponding to 40 μm separated histology slices- closely approximated full-volume micro-CT estimates of oocyte density. Analysis based on only five virtual sections aligned with micro-CT data exclusively in pediatric samples with high oocyte density, whereas in adult samples it led to substantial inaccuracies in oocyte density estimation.

Conclusion: Micro-CT scanning combined with machine learning analysis represents a novel high-throughput and automated approach for estimating oocyte count in cryopreserved ovarian cortical samples. In addition, three-dimensional analysis offers valuable insights into oocyte localization and spatial distribution within the ovarian cortex, presenting a promising alternative to conventional histology for future clinical and research applications.

This study aimed to design, synthesize, and evaluate a peptide vaccine based on nanoliposomes loading multi-epitopes (PVNLME) of P53, WT1, and CA125. We selected the best epitope for each targeted protein and then, PVNLME was synthesized and characterized. Subsequently, BALB/c mice were randomly divided into two groups receiving 10 mg/ml or 100 mg/ml of PVNLME. Then, 100 µl of the vaccine were injected into each mouse every seven days for three consecutive weeks. In the fourth week, blood samples were taken, and both antibody titer and the serum level of different cytokines were measured. To further investigate, each mouse's serum sample was exposed to the OVCAR3 cell line. Subsequently, BAX to BCL2 gene expression ratio, cell viability, and apoptosis were evaluated. Finally, the efficacy of the peptide vaccine was analyzed in humanized PDX model mice. Based on Bioinformatics analysis, a merged peptide EENLRKKGEPHHELPPKKKKCKTCQRKFSRSDHLKTKKKDTTPSMTTSHGAESSS was selected as a multi-epitope peptide. We found that the size distribution of PVNLME was 72-198 nm with a mean size of 112 nm, zeta potential of + 30 mV, and 96% peptide loading. The level of cytokines and the titer of antibodies increased with increasing doses of PVNLME. Furthermore, we showed that this vaccine can increase the ratio expression of BAX /BCL2, which promotes apoptosis. Also, there was a decrease in cell viability and an increase in apoptosis rate in both doses and exposure times. Following the administration of this multi-epitope vaccine in PDX humanized mice, a notable reduction in the tumor volume was observed.