RESEARCH Open Access
Polycystic ovarian syndrome is accompanied by
repression of gene signatures associated with
biosynthesis and metabolism of steroids,
cholesterol and lipids
Dessie Salilew-Wondim
1
, Qi Wang
2,3
, Dawit Tesfaye
1
, Karl Schellander
1
, Michael Hoelker
1
, Md Munir Hossain
4
and Benjamin K Tsang
2,3,5*
Abstract
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 83 μg5α-dihydrotestosterone (DHT) per day for
12 weeks to mimic the hyperandrogenic state in women with PCOS. The animals were euthanized at 15 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.
(Continued on next page)
* Correspondence: btsang@ohri.ca
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
Full list of author information is available at the end of the article
© 2015 Salilew-Wondim et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the
Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public
Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this
article, unless otherwise stated.
Salilew-Wondim et al. Journal of Ovarian Research (2015) 8:24
DOI 10.1186/s13048-015-0151-5