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Altered expression of miRNAs in a dihydrotestosterone-induced rat PCOS model

BACKGROUND: The polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine condition characterized by hyperandrogenism, hyperinsulinemia, insulin resistance and chronic anovulation. Regulation and interaction of a multitude of genes required for follicular development are found to be...

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Autores principales: Hossain, Md Munir, Cao, Mingju, Wang, Qi, Kim, Ji Young, Schellander, Karl, Tesfaye, Dawit, Tsang, Benjamin K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682887/
https://www.ncbi.nlm.nih.gov/pubmed/23675970
http://dx.doi.org/10.1186/1757-2215-6-36
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author Hossain, Md Munir
Cao, Mingju
Wang, Qi
Kim, Ji Young
Schellander, Karl
Tesfaye, Dawit
Tsang, Benjamin K
author_facet Hossain, Md Munir
Cao, Mingju
Wang, Qi
Kim, Ji Young
Schellander, Karl
Tesfaye, Dawit
Tsang, Benjamin K
author_sort Hossain, Md Munir
collection PubMed
description BACKGROUND: The polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine condition characterized by hyperandrogenism, hyperinsulinemia, insulin resistance and chronic anovulation. Regulation and interaction of a multitude of genes required for follicular development are found to be altered in PCOS. MicroRNAs (miRNAs) mediate posttranscriptional gene regulation by binding to the 3´ untranslated region of mRNAs to either inhibit or enhance translation. However, the extent and regulation of miRNA expression in PCOS is poorly understood and the current study is the first to describe altered expression of miRNAs in PCOS. METHODS: A chronically androgenized [5α-dihydrotestosterone (DHT)-treated] rat model which recapitulates many of the phenotypes of human PCOS, and miRNA PCR array was used to investigate the expression of 349 miRNAs in DHT treated rat ovaries. The ovarian expression of several selected miRNAs was also analyzed by in situ localization experiment. RESULTS: DHT-treated rats exhibit increased body weight, disrupted estrus cyclicity, decreased insulin sensitivity and decreased ovarian weight, with the latter phenomenon readily rescued by gonadotropin treatment in vivo. In general, 24% of the 349 miRNAs investigated were found to be differentially expressed between DHT-treated and control rats. Most of the differentially expressed miRNAs were found to be predominantly localized in the theca cells of the follicles. In silico analysis of the potential target genes of dysregulated miRNAs revealed their possible involvement in various pathways in the regulation of ovarian function. CONCLUSION: Our current findings suggest that miRNAs are differentially regulated in hyperandrogenism, a condition possibly involved in the dysregulation of steroid hormone receptors and intra-ovarian factors, and that miRNAs may be involved in the etiology of PCOS.
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spelling pubmed-36828872013-06-15 Altered expression of miRNAs in a dihydrotestosterone-induced rat PCOS model Hossain, Md Munir Cao, Mingju Wang, Qi Kim, Ji Young Schellander, Karl Tesfaye, Dawit Tsang, Benjamin K J Ovarian Res Research BACKGROUND: The polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine condition characterized by hyperandrogenism, hyperinsulinemia, insulin resistance and chronic anovulation. Regulation and interaction of a multitude of genes required for follicular development are found to be altered in PCOS. MicroRNAs (miRNAs) mediate posttranscriptional gene regulation by binding to the 3´ untranslated region of mRNAs to either inhibit or enhance translation. However, the extent and regulation of miRNA expression in PCOS is poorly understood and the current study is the first to describe altered expression of miRNAs in PCOS. METHODS: A chronically androgenized [5α-dihydrotestosterone (DHT)-treated] rat model which recapitulates many of the phenotypes of human PCOS, and miRNA PCR array was used to investigate the expression of 349 miRNAs in DHT treated rat ovaries. The ovarian expression of several selected miRNAs was also analyzed by in situ localization experiment. RESULTS: DHT-treated rats exhibit increased body weight, disrupted estrus cyclicity, decreased insulin sensitivity and decreased ovarian weight, with the latter phenomenon readily rescued by gonadotropin treatment in vivo. In general, 24% of the 349 miRNAs investigated were found to be differentially expressed between DHT-treated and control rats. Most of the differentially expressed miRNAs were found to be predominantly localized in the theca cells of the follicles. In silico analysis of the potential target genes of dysregulated miRNAs revealed their possible involvement in various pathways in the regulation of ovarian function. CONCLUSION: Our current findings suggest that miRNAs are differentially regulated in hyperandrogenism, a condition possibly involved in the dysregulation of steroid hormone receptors and intra-ovarian factors, and that miRNAs may be involved in the etiology of PCOS. BioMed Central 2013-05-15 /pmc/articles/PMC3682887/ /pubmed/23675970 http://dx.doi.org/10.1186/1757-2215-6-36 Text en Copyright © 2013 Hossain et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Hossain, Md Munir
Cao, Mingju
Wang, Qi
Kim, Ji Young
Schellander, Karl
Tesfaye, Dawit
Tsang, Benjamin K
Altered expression of miRNAs in a dihydrotestosterone-induced rat PCOS model
title Altered expression of miRNAs in a dihydrotestosterone-induced rat PCOS model
title_full Altered expression of miRNAs in a dihydrotestosterone-induced rat PCOS model
title_fullStr Altered expression of miRNAs in a dihydrotestosterone-induced rat PCOS model
title_full_unstemmed Altered expression of miRNAs in a dihydrotestosterone-induced rat PCOS model
title_short Altered expression of miRNAs in a dihydrotestosterone-induced rat PCOS model
title_sort altered expression of mirnas in a dihydrotestosterone-induced rat pcos model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682887/
https://www.ncbi.nlm.nih.gov/pubmed/23675970
http://dx.doi.org/10.1186/1757-2215-6-36
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