ABSTRACT: Differential genes in adipocytes induced from polycystic ovary syndrome-derived and non- polycystic ovary syndrome-derived human embryonic stem cells
Project description:To explore the molecular mechanisms of obesity and insulin resistance in the patients with polycystic ovary syndrome (PCOS) at the level of human embryonic stem cells (hESCs).Three PCOS-derived and one non-PCOS-derived hESC lines were induced into adipocytes, and then total mRNA was extracted from these adipocytes. The differential genes between PCOS-derived and non-PCOS-derived adipocytes were identified with GeneChip, and then were validated with real-time PCR.There were 153 differential genes. Of the 153 genes, 91 genes were up-regulated and 62 down-regulated. Nuclear receptor subfamily 0, group B, member 2 (NR0B2) was an up-regulated gene, and GeneChip software system indicated that it was associated with obesity and diabetes. Three PCOS-derived and one non-PCOS-derived hESC lines were induced into adipocytes, and then total mRNA was extracted from these adipocytes. The differential genes between PCOS-derived and non-PCOS-derived adipocytes were identified with GeneChip, and then were validated with real-time PCR.
Project description:To explore the molecular mechanisms of obesity and insulin resistance in the patients with polycystic ovary syndrome (PCOS) at the level of human embryonic stem cells (hESCs).Three PCOS-derived and one non-PCOS-derived hESC lines were induced into adipocytes, and then total mRNA was extracted from these adipocytes. The differential genes between PCOS-derived and non-PCOS-derived adipocytes were identified with GeneChip, and then were validated with real-time PCR.There were 153 differential genes. Of the 153 genes, 91 genes were up-regulated and 62 down-regulated. Nuclear receptor subfamily 0, group B, member 2 (NR0B2) was an up-regulated gene, and GeneChip software system indicated that it was associated with obesity and diabetes.
Project description:Polycystic ovarian syndrome (PCOS) is the most common gynaecological endocrine disease in women of reproductive age, with a prevalence rate of more than 12%, and is characterised by sporadic ovulation or anovulation, hyperandrogenism and polycystic ovarian changes. Polycystic ovary syndrome has a complex clinical presentation and, in addition to affecting follicular development and reproductive endocrine levels in women of childbearing age, it also impairs early embryonic development, affecting pregnancy outcome and offspring health, but its pathogenesis is unclear. In this study, we constructed a mouse model of PCOS using late-gestational hyperandrogen exposure, and examined the reproductive endocrine phenotype and glycolipid metabolism phenotype in mice. We found that PCOS model mice exposed to dihydrotestosterone in late pregnancy could exhibit hyperandrogenic manifestations, presenting elevated vaginal-anal index and delayed puberty establishment, as well as disturbed estrous cycle in adulthood. Ovulation number, number of mature oocytes, fertilisation rate and number of blastocysts were significantly lower in PCOS model mice compared to control mice. Subsequently, we assessed the follicular development and embryonic development ability of the mice using superovulation and in vitro fertilisation experiments, and obtained preimplantation embryonic RNA expression profiles of PCOS mice by performing Smart-seqII RNA sequencing to explore the possible mechanisms by which PCOS affects preimplantation embryonic development and offspring health. Bioinformatics analyses showed that 160 differentially expressed genes were identified out of 12,165 genes in blastocyst samples from both groups of mice, of which calcium/calmodulin-dependent protein kinase II β (CAMK2B2), melanoma-associated antigen B2 (MAGEB2), and the ADAM metallopeptidase domain (Adam4) were significantly differentially between the polycystic ovary syndrome and control groups Expression. Functional enrichment analyses revealed that the differential genes were mainly associated with pathways such as glandular development, nephron development, organ development and receptor catabolism. Our current study highlights the deleterious effects of intrauterine exposure to hyperandrogenism on the expression of polycystic ovary syndrome in mice, as well as resulting in impaired development of their eggs and early embryos. These findings may provide valuable insights into the early prevention of polycystic ovary syndrome.
Project description:Lean polycystic ovary syndrome (PCOS) women have a greater proportion of android (abdominal) fat, increased numbers of small subcutaneous (SC) abdominal adipocytes and preferential intra-abdominal fat accumulation. This study examines whether abnormal gene expression of SC abdominal adipose stem cells (ASCs) from lean PCOS women underlies this altered abdominal adipose structure-function. In this dataset, we include the expression data obtained from PCOS and NL subcutaneous adipose tissue. Differential expression of at least 1.5-fold change (P<0.05) were obtained in 120 genes (48 upregulated, 72 downregulated) of SC abdominal ASCs from PCOS versus NL women
Project description:In vitro studies of subcutaneous (SC) abdominal adipose stem cells (ASC) from women with polycystic ovary syndrome (PCOS) show altered ASC commitment to preadipocytes and differentiation to mature adipocytes related to hyperandrogenism. The goal of the study is to use microarrays to examine whether SC abdominal ASC gene expression are altered in normal-weight PCOS women and correlated with hyperandrogenemia and/or insulin resistance, which are prevalent clinical pathologies of PCOS.
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 endometrium during the window of implantation between the PCOS and healthy subjects.
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:Normal-weight polycystic ovary syndrome (PCOS) women exhibit adipose tissue dysfunction in vivo accompanied by enhanced subcutaneous (SC) abdominal adipose stem cell (ASC) development to adipocytes with greater lipid accumulation per cell in vitro. The goal of this study was to determine whether this phenomenon is associated with abnormal adipogenic gene transcription using RNA-sequencing to examine differential transcription patterns in PCOS vs controls. We found enhanced activation of adipogenic and adipocyte function genes and decreased expression of genes within the Wnt signaling pathway. In this study we conclude that this altered expression of genes in PCOS cells may underlie their exaggerated lipid accumulation in vitro and could predispose to adipose dysfunction in vivo when caloric intake exceeds energy utilization.
