Mol. Hum. Reprod. Advance Access originally published online on January 13, 2009
Molecular Human Reproduction 2009 15(2):89-103; doi:10.1093/molehr/gan082
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Gene expression microarray profiles of cumulus cells in lean and overweight-obese polycystic ovary syndrome patients
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1The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev, Ben-Gurion University, Beer-Sheva 84105, Israel 2Fertility and IVF Unit, Soroka University Medical Center, Beer-Sheva 84101, Israel 3Bioinformatics Core Facility at the National Institute for Biotechnology in the Negev (NIBN), Ben-Gurion University, Beer-Sheva 84105, Israel 4Genetics Institute at Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University, PO Box 151, Beer-Sheva 84105, Israel
5 Corresponding author: Tel: +972 8-6403439; Fax: +972 8-6400042; Email: obirk{at}bgu.ac.il
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| 
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/β-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.
Key words: PCOS/cumulus/microarray/infertility/insulin resistance
The first two authors contributed equally to the study.
Recipient of the American Physician Fellowship for Medicine in Israel.
Submitted on October 6, 2008; resubmitted on December 6, 2008; accepted on December 19, 2008.