Mogrosisde V improves follicular development and ovulation in PCOS rats induced by letrozole and high-fat diet through promoting glycolysis
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ABSTRACT:
PROVIDER: PRJNA800423 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
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| SRR17737361_1.fastq.gz | Fastqsanger.gz | |||
| SRR17737361_2.fastq.gz | Fastqsanger.gz | |||
| SRR17737362_1.fastq.gz | Fastqsanger.gz | |||
| SRR17737362_2.fastq.gz | Fastqsanger.gz | |||
| SRR17737363_1.fastq.gz | Fastqsanger.gz |
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Project description:Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. In this study, we induced a PCOS rat model by oral administration of letrozole combined with a high-fat diet and then treated with mogroside V (MV) to evaluate the protective roles on endocrine and follicle development in PCOS rats and the underlying mechanisms. Purpose: To detect the difference of ovary transcriptome profiling between PCOS model and Control rat and to evaluate the effect of mogroside V on the transcriptome profiling of ovaries of PCOS model rats. Methods: Ovarian mRNA profiles of 15-week-old Control, PCOS and PCOS-MV group rats (4 rats per group) were generated by deep sequencing,using Illumina PE150.
2022-04-20 | GSE194398 | GEO
Project description:Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease which leads to serious impairment of reproductive health in women of child-bearing age. Anovulation or oligo-ovulation is a common clinical manifestation of PCOS patients. The disturbance of ovarian immune microenvironment contributes to the disorders of follicle development and ovulation, and the mechanism remains unclear. Here we demonstrated the protective effect of immune factor interleukin-22 (IL-22) on PCOS follicle development and ovulation. Follicular IL-22 levels were significantly lower in PCOS patients than in the control group and were positively correlated with the oocyte fertilization rate and the high-quality embryo rate. Additionally, IL-22 evidently improved follicle development in vitro and promoted ovulation-related gene expression, which was disrupted by the depletion of interleukin-22 receptor 1 (IL-22R1) or inhibition of STAT3 in granulosa cells, indicating that IL-22 acted through IL-22R1 and STAT3 signalling pathway to promote follicle development and ovulation in PCOS. In summary, this study elucidated the vital role of ovarian immune microenvironment in follicle development and ovulation, the application of IL-22 may provide new insights into the treatment of PCOS patients.
2024-10-09 | GSE266340 | GEO
Project description:Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. In this study, we induced a young-adult PCOS rat model by oral administration of letrozole combined with a high-fat diet and then treated with mogroside V (MV) to evaluate the protective effects of MV on endocrine and follicle development in young-adult PCOS rats. MV (600 mg/kg/day) administration not only significantly reduced the body weight and ovary weight, but also attenuated the disrupted estrous cycle and decreased the level of testosterone. MV restored the follicular development, especially by increasing the number of corpus luteum and the thickness of the granular layer in young-adult POCS rats. Moreover, metabolomics showed that MV markedly increased the levels of D-Glucose 6-phosphate, lactate and GTP, while decreased the level of pyruvate. Bioinformatic analysis revealed that MV recovered multiple metabolism-related processes including gluconeogenesis, glycolysis and glucose metabolic process. Further real-time quantitative PCR analysis showed that MV upregulated the expression of lactate dehydrogenase A (Ldha), hexokinase 2 (Hk2) and pyruvate kinase M2 (Pkm2). Western blotting and immunohistochemistry analysis showed that MV restored the expression of lactate dehydrogenase A (Ldha), hexokinase 2 (Hk2) and pyruvate kinase M2 (Pkm2). Collectively, these findings indicated that MV could effectively improve the ovarian microenvironment by upregulating the expression of LDHA, HK2 and PKM2 in granulosa cells and enhancing lactate and energy production, which may contribute to follicle development and ovulation of young-adult PCOS rats.
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Project description:Roxadustat alleviates metabolic traits in letrozole-induced PCOS mice
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Project description:Polycystic ovary syndrome (PCOS) is a highly prevalent disorder, affecting one in eight women across the world. It is commonly accompanied by metabolic syndrome, including obesity, insulin resistance, impaired glucose tolerance and dyslipidemia. Activation of the hypoxia-inducible factor (HIF) pathway is known to alleviate metabolic defects and counteract obesity. Hence, this study utilized a preclinical PCOS mouse model to investigate the effects of chemically induced HIF activation on the metabolic traits of the syndrome.
2024-09-13 | GSE261300 | GEO
Project description:To compare the expression levels of long non-coding RNA (lncRNA) and messenger RNA (mRNA) in endometrium between patients with Polycystic Ovary Syndrome （PCOS）and normal ovulation undergoing in vitro fertilization-embryo transfer (IVF-ET） LncRNAs and mRNAs of endometrium were identified via RNA sequencing from 3 PCOS and 3 normal ovulation
2023-03-06 | GSE226146 | GEO
Project description:Ovulation disorder is the main characteristic of polycystic ovary syndrome (PCOS), but the concrete molecular mechanism is unclear. Phosphoglycerate kinase 1 (PGK1) plays an important role in the process of glycolytic cycles. Androgen and androgen receptor (AR) are considered as one of the critical factors in the prevalence of hyperandrogenemia and follicular development, and whether PGK1 participates in the metabolic reaction via AR in PCOS remains vague. PGK1 and AR proteins were highly expressed in PCOS luteinized granulosa cells and the PCOS-like mice ovary tissues. PGK1 increased lactate levels and deteriorated PCOS-like mouse metabolic disorder, and importantly, the phenotype of PCOS-like mice was rescued by PTX (paclitaxel) and the PGK1 and AR protein levels also decreased in the ovary. We demonstrated that PGK1 promoted AR translocation into the nuclear, and PGK1 was dependent on the E3 ligase Skp2 to repress the AR ubiquitination to improve the AR stability. In addition, we found that follicular development critical genes MAP2K6, KLF15, LRIG3 and MYOF were regulated by the PGK1-AR axis in the RNA-seq data, and axis also mediated cell proliferation and apoptosis. This study highlights the glycolysis key gene PGK1 to regulate metabolism in granular cell result in etiology of the PCOS. The PGK1-AR axis might provide a new therapy target of PCOS
2020-10-28 | GSE146856 | GEO
Project description:Vitrification is a method for long-term biological sample cryopreservation without causing intra- and extra-cellular ice formation. We recently established a novel closed vitrification system to cryopreserve mouse ovarian follicles. Using the 3D alginate hydrogel encapsulated in vitro follicle growth (eIVFG) method, we have demonstrated that compared to freshly-harvested follicles, vitrified follicles have normal follicle and oocyte reproductive outcomes. Our recent study further demonstrated the faithful preservation of molecular signatures of follicle-stimulating hormone (FSH)-stimulated follicle maturation in vitrified follicles. However, it is unknown whether ovulation, another crucial gonadotropin-dependent follicular event, and involved ovulatory gene regulatory pathways are well conserved in vitrified follicles. Fresh and vitrified follicles grown for 8 days by eIVFG were collected at 0, 1, 4 and 8-hour post human chorionic gonadotropin (hCG) treatment for the single-follicle RNA sequencing. Principal component analysis (PCA) and Pearson’s correlation analysis revealed that vitrified follicles have similar transcriptomic profiles to fresh follicles. Furthermore, the expression of several genes essential for ovulation were comparable between vitrified and fresh follicles. In summary, these results demonstrate that our closed vitrification system preserves follicular transcriptomic dynamics during ex vivo ovulation. Together with our previous findings that vitrification preserves FSH-stimulated follicle maturation, the integration of vitrification of immature follicles and eIVFG has a great potential to serve as an additional fertilization preservation approach for young cancer patients and endangerers species. Moreover, follicle vitrification enables a high-content ovarian follicle biobank, which can greatly improve the throughput of eIVFG for studying ovulation biology, anovulatory disease, toxicology, and novel contraceptive drug development targeting ovulation.
2023-09-20 | GSE227091 | GEO
Project description:Polycystic ovarian syndrome (PCOS) is characterized by hyperandrogenism, irregular ovulation and polycystic ovaries. In the present study, we utilized integrated analysis of whole transcriptome and DNA methylome by reduced representation bisulfite sequencing (RRBS) and RNA sequencing (RNA-seq) of the fetal side of placenta in women with PCOS. A cluster of neural function related genes, such as LIN7A and MAP1B, were identified with integrative analysis of methylome and transcriptome. Inflammatory disease and response process were spotlighted with GO enrichments analysis of differentially transcriptional gene cluster in PCOS, and the cellular growth and the development and function of nervous and endocrine system were also closely related to PCOS. With respect to neural function, the enriched GO terms in differential expressed gene cluster of PCOS group involved brain development, the proliferation and differentiation of neural precursor cell, neuron and neuroblast. Consistently, the enriched GO terms in differential methylated gene cluster of PCOS group were associated with neuropeptide and synaptic transmission, as well as cognition and learning or memory. As the gene expression changes in hypothalamus and hippocampus probably result in long standing neurobehavioural consequences in rodents, we conducted a global analysis of transcriptomic data of F1 pubertal female rats born to PCOS rats.
2020-08-12 | GSE154274 | GEO
Project description:BACKGROUND:Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disease with unknown pathogenesis. However, the treatment of Diane-35 combined with metformin can improve the endocrine and ovulation of PCOS. In this study, we investigated the effects of Diane-35 combined with metformin (DM) treatment on ovulation and glucose metabolism in a PCOS rat model. METHODS:Sprague Dawley rats were divided into 3 groups, control group, model group (PCOS group) and Diane-35 combined with metformin (PCOS + DM group). The mRNA expression levels were determined by qRT-PCR. The hormone levels were determined by enzyme-linked immunosorbent assay. Immunostaining detected the protein levels of lactate dehydrogenase A (LDH-A), pyruvate kinase isozyme M2 (PKM2) and sirtuin 1 (SIRT1) in the ovarian tissues. TNUEL assay was performed to determine cell apoptosis in the PCOS rats. The metabolites in the ovarian tissues were analyzed by liquid chromatography with tandem mass spectrometry. RESULTS:PCOS rats showed an increased in body weight, levels of luteinizing hormone and testosterone and insulin resistance, which was significantly attenuated by the DM treatment. The DM treatment improved disrupted estrous cycle and increased the granulosa cells of the ovary in the PCOS rats. The decreased proliferation and increased cell apoptosis of granulosa cells in the ovarian tissues of PCOS rats were significantly reversed by the DM treatment. The analysis of metabolics revealed that ATP and lactate levels were significantly decreased in PCOS rats, which was recovered by the DM treatment. Furthermore, the expression of LDH-A, PKM2 and SIRT1 was significantly down-regulated in ovarian tissues of the PCOS rats; while the DM treatment significantly increased the expression of LDH-A, PKM2 and SIRT1 in the ovarian tissues of the PCOS rats. CONCLUSION:In conclusion, our study demonstrated that Diane-35 plus metformin treatment improved the pathological changes in the PCOS rats. Further studies suggest that Diane-35 plus metformin can improve the energy metabolism of the ovary via regulating the glycolysis pathway. The mechanistic studies indicated that the therapeutic effects of Diane-35 plus metformin treatment in the PCOS rats may be associated with the regulation of glycolysis-related mediators including PKM2, LDH-A and SIRT1.
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