Identification and Functional Verification of MicroRNAs in the Obese Rat With Erectile Dysfunction

Yunlong Bai; Liangshuan Zhang; Yanan Jiang; Jiaming Ju; Guiyang Li; Juan Xu; Xing Jiang; Peng Zhang; Linchuan Lang; Olga Sadkovaya; Peter V Glybochko; Wei Zhang; Baofeng Yang

doi:10.1016/j.esxm.2017.06.006

Identification and Functional Verification of MicroRNAs in the Obese Rat With Erectile Dysfunction

Sex Med. 2017 Dec;5(4):e261-e271. doi: 10.1016/j.esxm.2017.06.006. Epub 2017 Sep 29.

Authors

Yunlong Bai¹, Liangshuan Zhang², Yanan Jiang², Jiaming Ju³, Guiyang Li², Juan Xu⁴, Xing Jiang², Peng Zhang², Linchuan Lang², Olga Sadkovaya⁵, Peter V Glybochko⁵, Wei Zhang³, Baofeng Yang⁶

Affiliations

¹ Department of Pharmacology, State Province Key Laboratories of Biomedicine and Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, People's Republic of China. Electronic address: baiyunlong@ems.hrbmu.edu.cn.
² Department of Pharmacology, State Province Key Laboratories of Biomedicine and Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, People's Republic of China.
³ North China Translational Medicine Research and Cooperation Center, Harbin Medical University, Harbin, People's Republic of China.
⁴ College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, People's Republic of China.
⁵ Sechenov First Moscow State Medical University, Moscow, Russia.
⁶ Department of Pharmacology, State Province Key Laboratories of Biomedicine and Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, People's Republic of China; Department of Pharmacology and Therapeutics, Melbourne School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.

Abstract

Introduction: Obesity is a potential risk factor for erectile dysfunction (ED). MicroRNAs (miRNAs) regulate the expression of genes involved in various pathophysiologic processes.

Aim: To identify the miRNA profile in the corpus cavernosum (CC) of obese rats with ED and elucidate the potential function of miRNA in the pathogenesis of ED.

Methods: Obesity was induced in rats by a high-fat diet. After the erectile function test, experimental animals were divided into two groups: obese rats with ED and obese rats with normal erectile function. The CCs from these rats were collected for miRNA microarray analysis. The results were verified by real-time polymerase chain reaction analysis. Subsequently, the targets of differentially expressed miRNAs were predicted. Bioinformatics analysis was applied to predict the functions of differentially expressed miRNAs in ED. Apomorphine-induced penile erection and intracavernous pressure measurements were used to evaluate the effects of miRNA on the erectile function of rats.

Main outcome measures: MiRNA expression in the CC of obese rats with ED and those with normal erectile function was detected by miRNA microarray analysis. Candidate miRNAs were validated by real-time polymerase chain reaction. Bioinformatics analysis was used to predict the functions of miRNAs. Apomorphine-induced penile erection and intracavernous pressure measurements were used to reflect the erectile function of rats.

Results: Sixty-eight miRNAs were differentially expressed in the CC of obese rats with ED (≥1.5-fold change). The real-time polymerase chain reaction results were consistent with the miRNA microarray analysis results. Specifically, miR-328a was significantly upregulated in rats with ED compared with control rats and was chosen for functional evaluation in the pathogenesis of ED. Overexpression of miR-328a noticeably decreased the erectile response to apomorphine and the expression of heme oxygenase-1.

Conclusion: MiRNAs are involved in the pathogenesis of obesity-related ED. MiR-328a might facilitate the induction of ED. Bai Y, Zhang L, Jiang Y, et al. Identification and Functional Verification of MicroRNAs in the Obese Rat With Erectile Dysfunction. Sex Med 2017;5:e261-e271.

Keywords: Erectile Dysfunction; MiR-328a; MicroRNA Microarray Analysis; Obesity.