Project description:Polycystic ovary syndrome (PCOS) is a common gynaecological disorder, characterised by elevated circulating androgens and increased expression of androgen receptor (AR) and by downregulation of Wilms Tumour 1 in the endometrium, The objectives of this study are: 1) Understand the functional role of WT1 in regulating decidualization response in healthy endometrial tissue, and 2) understand how interactions between aberrant WT1 and AR expression in PCOS patients result in dysregulation of deciduallization processes
Project description:Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women resulting in ovulation failure and other metabolic problems. However, the underlying mechanisms of it remain largely uncertain due to its complexity of clinical manifestations. Since PCOS is believed as a systemic disorder involved endocrine, metabolism, immune system and many organs, we therefore want to know what happen in the peripheral blood of patients with PCOS. To this purpose, gene expression patterns of peripheral blood from 10 PCOS patients and 10 healthy women were profiled by microarray. The significance analysis of microarray (SAM) software was employed to screen the differentially expressed genes (DEGs) and gene ontology (GO) was used for functional enrichment analysis. Also, quantitative reverse-transcription PCR (qRT-PCR) was performed to confirm the results from microarray. 181 DEGs with a fold change >2.0 and q-value <0.05 were identified between the groups. Of these genes, 149 were up-regulated and 32 down-regulated in PCOS. Importantly, 14 genes associated with inflammatory response pathway were highly enriched in PCOS. Furthermore, qPCR assays validated the dysregulated inflammatory response genes. Our observation reinforces the hypothesis that PCOS is characterized by the presence of systemic inflammatory changes and inflammation is implicated in the pathogenesis of this entity. Further elucidation of the aberrant expression of inflammation-related genes how to affect the pathogenesis of PCOS may lead to the development of novel preventative and therapeutic strategies.
Project description:Polycystic ovary syndrome is the most common endocrine condition in women and anovulatory cause of female infertility. While a pro-inflammatory cytokines and leukocyte bias in systemic circulation is well-documented in PCOS, it is not known how this inflammation extends to or affects the ovary. Additionally, the relationship between ovulation and inflammation in PCOS is not well-defined. We hypothesize that the ovarian follicular immune environment in PCOS is uniquely dysregulated, and that resolving anovulation through ovulation induction is not sufficient to alleviate this dysregulation. Using single-cell RNA and surface protein analysis of peripheral blood and follicular fluid from patients undergoing in vitro fertilization, we discovered that both control and PCOS follicles were immunologically distinct from circulation. At a systemic level, we find that ovulation induction in PCOS does not alleviate systemic inflammation. In contrast, while healthy control ovaries experienced acute immune-directed ovulatory signaling, PCOS ovarian follicles were deficient in key pro-ovulatory cell to cell communication, and displayed instead a chronic low-grade inflammatory state with fibrotic features. Taken together, a picture emerges where acute ovulation demonstrates a well-ordered series of follicle-specific immune information flows, which are disrupted and replaced by low grade chronic inflammation in the PCOS follicle.
Project description:Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovarian dysfunction and polycystic ovarian morphology and is classically considered as a disorder of the hypothalamic-pituitary-gonadal (HPG) axis. However, whether organs beyond the reproductive endocrine axis contribute to PCOS pathogenesis remains elusive. Herein, we identified a functional thymus-ovary axis involved in PCOS development.
Project description:Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovarian dysfunction and polycystic ovarian morphology and is classically considered as a disorder of the hypothalamic-pituitary-gonadal (HPG) axis. However, whether organs beyond the reproductive endocrine axis contribute to PCOS pathogenesis remains elusive. Herein, we identified a functional thymus-ovary axis involved in PCOS development.
