Gene expression profiling of cumulus cells isolated from MII oocytes of Iranian patients with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is a multifactorial, complex genetic, endocrine and metabolic disorder. It is clearly a heterogeneous syndrome, characterized by chronic anovulation, polycystic ovaries and biochemical and clinical manifestations of hyperandrogenism. PCOS is probably the most common cause of anovulatory infertility, associated with an increased risk of miscarriage after either spontaneous or assisted conception. However, with the recent technological advancements such as assisted reproductive technology (ART) that has been created to overcome the problem of infertility; these techniques are still expensive, and the success rate is low. Poor oocyte quality is the main cause of fertilization failure in ARTs. The selection of oocytes with the highest developmental potential for in vitro maturation (IVM) and in vitro fertilization (IVF) is currently based on morphological criteria, but it is generally acknowledged that its reliability requires further improvement. There is increasing evidence that communication between the oocyte and its surrounding cumulus cells (CCs) is vital for folliculogenesis and oocyte developmental competence acquisition. In this regard, it has been proposed that transcriptomic analysis of CCs will able us to predict oocyte developmental competence, as well as embryo and pregnancy outcomes during ART procedures (e.g., IVM and IVF).Objective: Therefore, the aim of the present study was to use a non-invasive method in identifying potential oocyte developmental competence biomarkers for the selection of the best oocyte from women with PCOS; and the use of this oocyte to increase IVF success rates.Materials and Methods: CCs from oocytes in metaphase II (MII) stage of PCOS and non-PCOS patients who underwent controlled ovarian stimulation were mechanically removed shortly before ICSI. Gene expression profiles were analyzed using the RNA-sequencing (RNA-seq) technology. Sequence reads were obtained from an Illumina HiSeq2500 platform and mapped onto the human genome (hg19) using TopHat aligner. The known gene annotation, functional annotation and gene-set enrichment analysis were performed using GO and KEGG databases on differentially expressed genes (DEGs) of CCs from PCOS and non-PCOS patients.Results: The analysis of these RNA-seq data identified 59 genes that were differentially modulated in the two CC groups, including 42 genes that were up-regulated and 17 genes that were down-regulated in CC samples from patients with PCOS in comparison with patients without PCOS. Some of these genes were identified to be involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation, oocyte maturation and regulation of luteinizing hormone.Conclusion: Gene expression profiles showed clear difference between CCs from non-PCOS and those from PCOS patients. This study identified candidate genes involved in cell cycle progression and differentiation and also oocyte maturation that may influence the function of granulosa cells in PCOS patients. Our results may be clinically important as they offer a new potential strategy for competent oocyte/embryo selection in PCOS patients.

Keywords:

Polycystic ovary syndrome , Cumulus cells , Gene expression , RNA-sequencing , Non-invasive biomarkers