Polycystic ovarian syndrome is accompanied by repression of gene signatures associated with biosynthesis and metabolism of steroids, cholesterol and lipids
Research
1 Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, Endenicher Allee 15, Bonn 53115, Germany
2 Reproductive Biology Unit and Division of Reproductive Medicine, Department of Obstetrics Gynecology and Cellular Molecular Medicine, Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa K1H 8L6, ON, Canada
3 Chronic Disease Program, Ottawa Hospital Research Institute, The Ottawa Hospital (General Campus), Critical Care Wing, 3rd Floor, Room W3107, 501 Smyth Road, Ottawa K1H 8L6, ON, Canada
4 Department of Animal Breeding and Genetics, Bangladesh Agricultural University, Mymensingh 2202, Bangladesh
5 Department of Agricultural Biotechnology, World Class University Major in Biomodulation, College of Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea
Journal of Ovarian Research 2015, 8:24Â
doi:10.1186/s13048-015-0151-5
Published: 13 April 2015
Abstract (provisional)
Background Polycystic ovarian syndrome (PCOS) is a spectrum of heterogeneous disorders
of reproduction and metabolism in women with potential systemic sequel such as diabetes
and obesity. Although, PCOS is believed to be caused by genetic abnormalities, the
genetic background that can be associated with PCOS phenotypes remains unclear due
to the complexity of the trait. In this study, we used a rat model which exhibits
reproductive and metabolic abnormalities similar to the human PCOS to unravel the
molecular mechanisms underlining this complex syndrome. Methods Female Sprague–Dawley
rats were randomly assigned to DHT and control (CTL) groups. Rats in the DHT group
were implanted with a silicone capsule continuous-releasing 83Â ?g 5?-dihydrotestosterone
(DHT) per day for 12Â weeks to mimic the hyperandrogenic state in women with PCOS.
The animals were euthanized at 15Â weeks of age and the pairs of ovaries were excised
and the ovarian cortex tissues were used for gene expression analysis. Total RNA was
from the ovarian cortex was amplified, labeled and hybridized to the Affymetrix GeneChip®
Rat Genome 230 2.0 Array. A linear model system for microarray data analysis was used
to identify genes affected in DHT treated rat ovaries and the molecular pathway of
those genes were analyzed using the Database for Annotation, Visualization and Integrated
Discovery (DAVID) analysis tool. Results A total of 573 gene transcripts, including
CPA1, CDH1, INSL3, AMH, ALDH1B1, INHBA, CYP17A1, RBP4, GAS6, GAS7 and GATA4, were
activated while 430 others including HSD17B7, HSD3B6, STAR, HMGCS1, HMGCR, CYP51,
CYP11A1 and CYP19A1 were repressed in DHT-treated ovaries. Functional annotation of
the dysregulated genes revealed that biosynthesis and metabolism of steroids, cholesterol
and lipids to be the most top functions enriched by the repressed genes. However,
cell differentiation/proliferation, transcriptional regulation, neurogenesis, cell
adhesion and blood vessel development processes were enriched by activated genes.
Conclusion The dysregulation of genes associated with biosynthesis and metabolism
of steroids, cholesterol and lipids, cell differentiation/proliferation in DHT- treated
ovaries could be a molecular clue for abnormal steroidogenesis, estrous cycle irregularity,
abnormal folliculogenesis, anovulation and lipid metabolism in PCOS patients.