Molecular abnormalities in oocytes from women with polycystic ovary syndrome revealed by microarray analysis

Context: Polycystic ovary syndrome ( PCOS), the most common cause of anovulatory infertility, is characterized by increased ovarian androgen production and arrested follicle development and is frequently associated with insulin resistance. These PCOS phenotypes are associated with exaggerated ovarian responsiveness to FSH and increased pregnancy loss. Objective: The objective of this study was to examine whether the perturbations in follicle growth and the intrafollicular environment affect gene expression and ultimately development of the PCOS oocyte. Design: Oocyte cDNA was subjected to microarray and PCR analysis. Setting: This study was conducted at a university laboratory. Patients: The study comprised 10 normal ovulatory women and nine women with PCOS. Intervention: The intervention was GnRH analog/ recombinant human FSH therapy for in vitro fertilization. Main Outcome Measure: The main outcome measure was mRNA abundance of oocyte-expressed genes. Results: Cluster analysis revealed differences in global gene expression profiles between normal and PCOS oocytes. Of the 8123 transcripts expressed in the oocytes, 374 genes showed significant differences in mRNA abundance in PCOS oocytes. Annotation of the data demonstrated that a subset of these genes was associated with chromosome alignment and segregation during mitosis and/or meiosis. Furthermore, 68 of the differentially expressed genes contained putative androgen receptor and/or peroxisome proliferating receptor gamma binding sites. Conclusions: These analyses demonstrated that normal and PCOS oocytes that are morphologically indistinguishable and of high quality exhibit different gene expression profiles. Promoter analysis suggests that androgens and other activators of nuclear receptors may play a role in differential gene expression in the PCOS oocyte. Likewise, annotation of the differentially expressed genes suggests that defects in meiosis or early embryonic development may contribute to reduced developmental competency of PCOS oocytes.