Zhang Lixin, Liu Zhineng, Li Xiaokang, Zhang Ping, Wang Jia, Zhu Dandan, Chen Xinping, Ye Lihua
Department of Reproductive Medicine, Taizhou People's Hospital Affiliated of Nantong University of Medicine Taizhou 225300, China.
Int J Clin Exp Pathol. 2015 Nov 1;8(11):14198-205. eCollection 2015.
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.
HOTAIR是一种长链非编码RNA，可调节肿瘤细胞的发育和进展以及正常干细胞的功能。然而，HOTAIR在弱精子症和少弱精子症患者精子中的作用及分子机制仍不清楚。本研究纳入了45名健康对照者、45名弱精子症患者和45名少弱精子症患者。首先，通过分析HOTAIR表达，我们观察到患者中HOTAIR表达水平降低。随后，我们发现患者中HOTAIR表达与Nrf2表达呈正相关。还观察到HOTAIR的低表达与特定的精子功能参数有关，包括活力和存活率。在患者射出的精子中，观察到Nrf2基因启动子的组蛋白H4乙酰化水平较低。最后，我们发现HOTAIR表达下调会降低Nrf2启动子中的组蛋白H4乙酰化和Nrf2表达。因此，本研究表明，弱精子症和少弱精子症患者的精子中HOTAIR表达较低，这导致Nrf2表达下调。我们的数据表明，HOTAIR表达的降低导致了精子功能中与活性氧相关的缺陷。
