miR-424/322 is downregulated in the semen of patients with severe DNA damage and may regulate sperm DNA damage
Kai Zhao A , Yaoping Chen A , Ruifeng Yang A , Yang Bai B , Cuiling Li A , Honggang Li A B C and Chengliang Xiong A B C
+ Author Affiliations
- Author Affiliations
A Family Planning Research Institute/Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
B Wuhan Tongji Reproductive Medicine Hospital, Wuhan 430014, China.
C Corresponding authors. Emails: lhgyx@hotmail.com; clxiong951@sina.cn
Reproduction, Fertility and Development 28(10) 1598-1607 https://doi.org/10.1071/RD15052
Submitted: 3 October 2014 Accepted: 6 March 2015 Published: 15 April 2015
Abstract
Sperm DNA integrity is an essential factor for accurate transmission of genetic information. Human sperm DNA damage is a common cause of male infertility but the exact mechanism remains poorly understood. Considering the vital role of microRNA (miRNA) in multiple pathophysiological processes, we hypothesised that testicular miRNA is involved in sperm DNA damage during spermatogenesis. Infertile patients with high sperm DNA fragment index (DFI; n = 94) were selected from 1090 infertile men and a total of 18 testis-specific seminal miRNAs previously identified from human seminal plasma were chosen and tested. miR-29c and miR-424 were downregulated in men with high DFI. The inhibition of these two miRNAs in mice confirmed the role of miR-424 (murine homologue miR-322) in sperm DNA damage during spermatogenesis; by contrast, miR-29c exhibited a negative result. Thus, miR-424/322 is involved in sperm DNA damage. Furthermore, the dysregulation of this miRNA can induce DNA double-strand breaks during spermatogenesis.
Additional keywords: cell-free RNA, microRNA, spermatogenesis.
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