Reproductive Biology Unit and Division of Reproductive Medicine, Department of Obstetrics & Gynecology and Cellular & Molecular Medicine, University of Ottawa; Chronic Disease Program, Ottawa Hospital Research Institute, The Ottawa Hospital (General Campus), Ottawa, ON K1H 8L6, Canada.
J Ovarian Res. 2013 May 15;6(1):36. doi: 10.1186/1757-2215-6-36.
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.
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.
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.
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.
多囊卵巢综合征（PCOS）是一种复杂且异质性的内分泌疾病，其特征为高雄激素血症、高胰岛素血症、胰岛素抵抗和慢性无排卵。现已发现，多囊卵巢中卵泡发育所必需的多种基因的调控和相互作用发生改变。微小 RNA（miRNA）通过与 mRNAs 的 3´非翻译区结合来介导转录后基因调控，从而抑制或增强翻译。然而，PCOS 中 miRNA 表达的程度和调控仍知之甚少，本研究首次描述了 PCOS 中 miRNA 的表达改变。
本研究使用慢性雄激素化[5α-二氢睾酮（DHT）处理]大鼠模型来模拟人类 PCOS 的许多表型，并使用 miRNA PCR 阵列来研究 DHT 处理大鼠卵巢中 349 种 miRNA 的表达。还通过原位定位实验分析了几种选定 miRNA 的卵巢表达。
DHT 处理的大鼠表现出体重增加、发情周期紊乱、胰岛素敏感性降低和卵巢重量降低，后者通过体内给予促性腺激素治疗很容易得到挽救。总的来说，在所研究的 349 种 miRNA 中，有 24%被发现存在于 DHT 处理的大鼠与对照组大鼠之间的差异表达。大多数差异表达的 miRNA 主要定位于卵泡的间质细胞中。对失调 miRNA 的潜在靶基因进行计算机分析表明，它们可能参与了调节卵巢功能的各种途径。
我们目前的研究结果表明，miRNA 在高雄激素血症中存在差异表达，这种情况可能与类固醇激素受体和卵巢内因子的失调有关，并且 miRNA 可能参与了 PCOS 的发病机制。
