Project description:As somatic cells surround the oocyte, the endocrine functions exerted by ovarian granulosa cells (GCs) are crucial factors in maintaining follicle development, as oocyte development relies on the provision of energy substrates and cytokines by ovarian granulosa cells. The mRNA deadenylase level of granulosa cells precisely regulates the transcription processes of key molecules involved in oocyte maturation. In this study, we detect the expression level of the deadenylase CNOT6L in PCOS patients' granulosa cells and mouse models' ovaries. We found that the CNOT6L significantly upregulated in the ovarian granulosa cells of both PCOS patients and mouse models. Subsequently, we overexpressed CNOT6L granulosa cells to explore the alternations by which CNOT6L regulates ovarian granulosa cell function. We also found that overexpression of CNOT6L in granulosa cells significantly inhibited the glycolytic pathway, activated the mitochondrial oxidative phosphorylation pathway, led to a reduction in the generation of the intermediate product lactate, and resulted in impaired energy supply to the oocyte. Subsequently, we performed Full-length transcriptome sequencing on the granulosa cells and investigated the impact of mRNA poly(A) level differences on granulosa cell dysfunction in PCOS. This study offers new insights into the role of Cnot6l in regulating energy metabolism homeostasis and its involvement in follicular developmental disorders related to polycystic ovary syndrome.
Project description:Polycystic ovary syndrome (PCOS), one of the most common endocrinal diseases among reproductive-aged women,is characterized by hyperandrogenemia, chronic oligo/anovulation and polycystic ovarian morphology. In this research, we presented microarrays to identify the differential expressed protein-coding genes and lncRNAs expression profile in the luteinized granulosa cells obtained from PCOS and healthy control patients.
Project description:Obese or polycystic ovary syndrome (PCOS) women have encountered poor reproductive outcomes in natural as well as assisted conception. Furthermore, pregnancy complications of women with PCOS are profoundly worsened by obesity. Both obesity and PCOS affect function of granulosa cells, which is essential in offering the oocyte with nutrients and growth regulators.
Project description:Polycystic ovary Syndrome (PCOS) is a heterogeneous endocrine disorder that shows evidence of genetic predidposition among affected individuals. We have utilized the Microarray data from granulosa cells of normal and PCOS women for network construction. Human granulosa cells were isolated from ovarian aspirates from normal and PCOS women undergoing IVF and for each sample, RNA was extracted and hybridized to an Affymetrix GeneChip.
Project description:Polycystic ovary Syndrome (PCOS) is a heterogeneous endocrine disorder that shows evidence of genetic predidposition among affected individuals. We have utilized the Microarray data from granulosa cells of normal and PCOS women for network construction.
Project description:Aberration in miRNA expression or DNA methylation is a causal factor for numerous pathological conditions including polycystic ovarian syndrome PCOS, a common endocrine disorders and leading cause of infertility. The epigenetic interactions between miRNA and DNA methylation remain unexplored in PCOS. Our study identifies epigenetic alternation in ovarian granulosa cells from PCOS patients and helps to reveal the pathogenesis of PCOS.
Project description:Aberration in miRNA expression or DNA methylation is a causal factor for numerous pathological conditions including polycystic ovarian syndrome PCOS, a common endocrine disorders and leading cause of infertility. The epigenetic interactions between miRNA and DNA methylation remain unexplored in PCOS. Few studies have reported that the regulation of miRNAs in polycystic ovary syndrome(PCOS). Our study helps to understand the molecular pathogenesis of PCOS in human ovarian granulosa cells from the perspective of post-transcriptional level.
Project description:Polycystic ovary syndrome (PCOS) is the most common complex endocrine and metabolic disease in women of reproductive age. It is characterized by anovulatory infertility, hormone disorders, and polycystic ovarian morphology. Regarding the importance of granulosa cells (GCs) in the pathogenesis of PCOS, few studies have investigated the etiology at a single “omics” level, such as with an mRNA expression array or methylation profiling assay, but this can provide only limited insights into the biological mechanisms. Here, genome-wide DNA methylation together with lncRNA-miRNA-mRNA profiles were simultaneously detected in GCs of PCOS cases and controls. A total of 3579 lncRNAs, 49 miRNAs, 669 mRNAs, and 890 differentially methylated regions (DMR)-associated genes were differentially expressed between PCOS cases and controls. Pathway analysis indicated that these differentially expressed genes were commonly associated with steroid biosynthesis and metabolism-related signaling, such as glycolysis/gluconeogenesis. In addition, we constructed ceRNA networks and identified some known ceRNA axes, such as lncRNAs-miR-628-5p-CYP11A1/HSD17B7. We also identified many new ceRNA axes, such as lncRNAs-miR-483-5p-GOT2. Interestingly, most ceRNA axes were also closely related to steroid biosynthesis and metabolic pathways. These findings suggest that it is important to systematically consider the role of reproductive and metabolic genes in the pathogenesis of PCOS.
Project description:Aberration in miRNA expression or DNA methylation is a causal factor for numerous pathological conditions including polycystic ovarian syndrome PCOS, a common endocrine disorders and leading cause of infertility. The epigenetic interactions between miRNA and DNA methylation remain unexplored in PCOS. Few studies have reported that the key genes and pathways involved in polycystic ovary syndrome(PCOS). Our study helps to understand the molecular pathogenesis of PCOS in human ovarian granulosa cells and identifiy genes and pathways that may be potential therapeutic targets for PCOS treatment..