Gene expression microarray profiles of cumulus cells in lean and overweight-obese polycystic ovary syndrome patients

Abstract

The aim of this work was to study gene expression patterns of cultured cumulus cells from lean and overweight-obese polycystic ovary syndrome (PCOS) patients using genome-wide oligonucleotide microarray. The study included 25 patients undergoing in vitro fertilization and intra-cytoplasmic sperm injection: 12 diagnosed with PCOS and 13 matching controls. Each of the groups was subdivided into lean (body mass index (BMI) < 24) and overweight (BMI > 27) subgroups. The following comparisons of gene expression data were made: lean PCOS versus lean controls, lean PCOS versus overweight PCOS, all PCOS versus all controls, overweight PCOS versus overweight controls, overweight controls versus lean controls and all overweight versus all lean. The largest number of differentially expressed genes (DEGs), with fold change (FC) |FC| >or= 1.5 and P-value < 0.01, was found in the lean PCOS versus lean controls comparison (487) with most of these genes being down-regulated in PCOS. The second largest group of DEGs originated from the comparison of lean PCOS versus overweight PCOS (305). The other comparisons resulted in a much smaller number of DEGs (174, 109, 125 and 12, respectively). In the comparison of lean PCOS with lean controls, most DEGs were transcription factors and components of the extracellular matrix and two pathways, Wnt/beta-catenin and mitogen-activated protein kinase. When comparing overweight PCOS with overweight controls, most DEGs were of pathways related to insulin signaling, metabolism and energy production. The finding of unique gene expression patterns in cumulus cells from the two PCOS subtypes is in agreement with other studies that have found the two to be separate entities with potentially different pathophysiologies.

Aberrant expression of long noncoding RNAs in cumulus cells isolated from PCOS patients

“…In this study, 623 lncRNAs and 260 mRNAs were differentially expressed between CC samples from PCOS and normal patients. The differentially expressed mRNAs (n=260) isolated in this study were not identical to those published in previous reports [2,13]. This difference may be due to differences in the samples (oocyte, ovarian tissue, or cumulus cells) and the gene chips between ours and the previous studies.…”

“…This difference may be due to differences in the samples (oocyte, ovarian tissue, or cumulus cells) and the gene chips between ours and the previous studies. Notably, because previous reports have shown that the lean PCOS group is the source of the unique characteristics of Bauthentic^PCOS and obesity may be regarded as modifier of the syndrome or as a separate pathological mechanism that results in similar consequences [13], we selected lean PCOS patients with lower BMI (21.6±1.5) in this study to reduce the differences in gene expression caused by obesity. In fact, PCOS in lean and obese individuals should be regarded as separate subentities.…”

“…Many studies have reported gene expression profiles based on tissues from PCOS and control patients. These studies utilized cDNA microarrays in theca cells [9], whole ovaries [10,11], oocytes [12], and cumulus cells [13]. The data from these studies revealed a number of the genes associated with PCOS are primarily involved in the insulin receptor signaling pathway, steroid biosynthesis, and the regulation of gonadotropin secretion [14].…”

Gene expression profiling of granulosa cells from PCOS patients following varying doses of human chorionic gonadotropin

“…These observations were further supported by subsequent studies that measured global gene expression of cumulus cells, which was concluded to be a non-invasive test for oocyte/embryo quality [2,3,15,41]. Granulosa and cumulus cell gene expression profiling has also been used to compare the effects of recombinant FSH vs. human menopausal gonadotrophin (hMG) [6,14], floating vs. cumulus granulosa cells [22], cumulus cells from lean vs. overweight-obese PCOS patients [21], and ovarian reserve status in young women with diminished ovarian reserve [39].…”

Granulosa cell biomarkers to predict pregnancy in ART: pieces to solve the puzzle

“…Patient BMI alters CC gene expression in both polycystic ovarian syndrome (PCOS) (Kenigsberg et al 2009) and non-PCOS women (Robker et al 2009). Therefore, studies with a large range of ages or BMIs may show DRGE profiles that would not exist if the age ranges or BMI were controlled for in the studies.…”