Low long non-coding RNA HOTAIR expression is associated with down-regulation of Nrf2 in the spermatozoa of patients with asthenozoospermia or oligoasthenozoospermia

Int J Clin Exp Pathol. 2015 Nov 1;8(11):14198-205. eCollection 2015.

Abstract

HOTAIR, a long noncoding RNA, regulates development and progression of tumor cells and function of normal stem cells. However, the role and the molecular mechanism of HOTAIR in the spermatozoa of patients with asthenozoospermia and oligoasthenozoospermia are still unclear. Herein, 45 healthy control, 45 asthenozoospermic patients and 45 oligoasthenozoospermic patients were enrolled. Initially, through analyzing HOTAIR expression, we observed a decreased level of HOTAIR expression in patients. Subsequently, we found that there was a positive correlation between HOTAIR expression and Nrf2 expression in patients. The low expression of HOTAIR was also observed to be associated with specific sperm function parameters, including motility and vitality. In the ejaculated spermatozoa from patients, low level of histone H4 acetylation of the Nrf2 gene promoter was observed. Finally, we found that downregulation of HOTAIR expression reduced histone H4 acetylation in Nrf2 promoter and Nrf2 expression. Therefore, this study demonstrated that HOTAIR expression was low in the spermatozoa of patients with asthenozoospermia and oligoasthenozoospermia, which resulted in down-regulation of Nrf2 expression. Our data suggested the decrease of HOTAIR expression led to ROS related defects in sperm function.

Keywords: HOTAIR; Nrf2; ROS; asthenozoospermia and oligoasthenozoospermia; histone acetylation.

MeSH terms

  • Acetylation
  • Adult
  • Asthenozoospermia / diagnosis
  • Asthenozoospermia / genetics
  • Asthenozoospermia / metabolism*
  • Asthenozoospermia / pathology
  • Case-Control Studies
  • Cell Line
  • Cell Survival
  • Down-Regulation
  • Histones / metabolism
  • Humans
  • Male
  • Middle Aged
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Oligospermia / diagnosis
  • Oligospermia / genetics
  • Oligospermia / metabolism*
  • Oligospermia / pathology
  • Promoter Regions, Genetic
  • RNA Interference
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Reactive Oxygen Species / metabolism
  • Sperm Motility
  • Spermatozoa / metabolism*
  • Spermatozoa / pathology
  • Superoxide Dismutase / metabolism
  • Transfection

Substances

  • HOTAIR long untranslated RNA, human
  • Histones
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • RNA, Long Noncoding
  • Reactive Oxygen Species
  • Superoxide Dismutase