Long non-coding RNAs (lncRNAs) in spermatogenesis and male infertility

Abstract

Background Long non-coding RNAs (lncRNAs) have a size of more than 200 bp and are known to regulate a host of crucial cellular processes like proliferation, differentiation and apoptosis by regulating gene expression. While small noncoding RNAs (ncRNAs) such as miRNAs, siRNAs, Piwi-interacting RNAs have been extensively studied in male germ cell development, the role of lncRNAs in spermatogenesis remains largely unknown. Objective In this article, we have reviewed the biology and role of lncRNAs in spermatogenesis along with the tools available for data analysis. Results and conclusions Till date, three microarray and four RNA-seq studies have been undertaken to identify lncRNAs in mouse testes or germ cells. These studies were done on pre-natal, post-natal, adult testis, and different germ cells to identify lncRNAs regulating spermatogenesis. In case of humans, five RNA-seq studies on different germ cell populations, including two on sperm, were undertaken. We compared three studies on human germ cells to identify common lncRNAs and found 15 lncRNAs (LINC00635, LINC00521, LINC00174, LINC00654, LINC00710, LINC00226, LINC00326, LINC00494, LINC00535, LINC00616, LINC00662, LINC00668, LINC00467, LINC00608, and LINC00658) to show consistent differential expression across these studies. Some of the targets of these lncRNAs included CENPB, FAM98B, GOLGA6 family, RPGR, TPM2, GNB5, KCNQ10T1, TAZ, LIN28A, CDKN2B, CDKN2A, CDKN1A, CDKN1B, CDKN1C, EZH2, SUZ12, VEGFA genes. A lone study on human male infertility identified 9879 differentially expressed lncRNAs with three (lnc32058, lnc09522, and lnc98497) of them showing specific and high expression in immotile sperm in comparison to normal motile sperm. A few lncRNAs (Mrhl, Drm, Spga-lncRNAs, NLC1-C, HongrES2, Tsx, LncRNA-tcam1, Tug1, Tesra, AK015322, Gm2044, and LncRNA033862) have been functionally validated for their roles in spermatogenesis. Apart from rodents and humans, studies on sheep and bull have also identified lncRNAs potentially important for spermatogenesis. A number of these non-coding RNAs are strong candidates for further research on their roles in spermatogenesis.

Changes in Phenotypes and DNA Methylation of In Vitro Aging Sperm in Common Carp Cyprinus carpio

“…The effect of environmental changes on the altered gene expression are largely implemented by the changes in the epigenome, which further interacts with a networks of DNA methylation reader proteins playing a role in a cascade of gene expression regulation. This assumption led to the identification of a sperm-specific catalogue of transcripts and characterization of gene expression profiles in normal [ 65 , 66 ] and infertile sperm in vertebrates which yielded several promising candidate transcripts that are currently in use as markers of male sperm quality and fertility [ 50 , 62 , 67 , 68 , 69 ]. The methylation changes that occurred in the subvital and aberrant sperm cells at 24 HPS might have been driven by the changes in the gene expression and thus by altered representation of transcripts that could have led to the observed hypermethylation with subsequent deterioration of sperm quality traits and eventual death of these cells.…”

Microinjection of Antisense Oligonucleotides into Living Mouse Testis Enables LncRNA Function Study

“…Besides, ASOs can act in the nucleus and intervene in transcription, which makes ASOs widely used in pre-clinical studies of singlegene disorders [56]. The method we established for ASO-mediated testis knockdown in vivo also offers possibility for pre-clinical application of ASOs in humans with regards to male contraception or improvement of reproductive health [57][58][59].…”

Long Non-Coding RNA LINC00467 Correlates to Poor Prognosis and Aggressiveness of Breast Cancer

“…LINC00467 (ID in NCBI database: 84791), a LncRNA has attracted much attention recently, was reported to be dysregulated in spermatogenesis and male infertility ( 11 , 12 ). Besides, it was also reported that LINC00467 expression was associated with Vogt-Koyanagi-Harada Disease and Behcet’s Disease ( 13 ).…”

“…In general, LncRNAs function via interacting with proteins, chromatin DNA or other types of RNAs to mediate their stability or activity in different aspects of tumor biology (7)(8)(9)(10). LINC00467 (ID in NCBI database: 84791), a LncRNA has attracted much attention recently, was reported to be dysregulated in spermatogenesis and male infertility (11,12). Besides, it was also reported that LINC00467 expression was associated with Vogt-Koyanagi-Harada Disease and Behcet's Disease (13).…”