Hypoxia-related long noncoding RNAs are associated with varicocele-related male infertility.

One of the main molecular causes that contributes to varicocele-related male infertility is excess production of reactive oxygen species (ROS). It is believed that hypoxia is an important stimulator of ROS in this condition. Recently, the significant roles of long non-coding RNAs (lncRNAs) in hypoxia response have emerged. Despite the investigation of hypoxia, there is scant information about the role of hypoxia-responding lncRNAs in varicocele-related male infertility. In the present study, we deduced eight hypoxia-responding lncRNAs based on high-throughput RNA sequencing data from two Gene Expression Omnibus (GEO) datasets. We used qRT-PCR to assess the expression levels of some of these lncRNAs in 42 ejaculated spermatozoa samples from 25 infertile men with varicocele and 17 fertile men as controls. We identified significant increases in expression levels of hypoxia-related lncRNAs, MIR210HG and MLLT4-AS1 in ejaculated spermatozoa of infertile men with varicocele. These lncRNAs also showed significant positive correlations with ROS levels and meaningful negative correlations with sperm parameters (count and motility). Besides, in silico studies identified several hypoxia response elements (HREs) within selected lncRNAs promoters. Delineation of hypoxia-related lncRNAs in varicocele-related infertility provides a valuable insight into male infertility.