Role of MicroRNAs in Controlling Gene Expression in Different Segments of the Human Epididymis

Abstract

BackgroundThe molecular mechanisms implicated in regionalized gene expression in the human epididymis have not yet been fully elucidated. Interestingly, more than 200 microRNAs (miRNAs) have been identified in the human epididymis and could be involved in the regulation of mRNA stability and post-transcriptional expression in this organ.MethodsUsing a miRNA microarray approach, we investigated the correlation between miRNA signatures and gene expression profiles found in three distinct regions (caput, corpus and cauda) of human epididymides from 3 donors. In silico prediction of transcript miRNA targets was performed using TargetScan and Miranda software's. FHCE1 immortalized epididymal cell lines were cotransfected with mimic microRNAs and plasmid constructs containing the 3′UTR of predicted target genes downstream of the luciferase gene.ResultsWe identified 35 miRNAs differentially expressed in the distinct segments of the epididymis (fold change ≥2, P-value≤0.01). Among these miRNAs, miR-890, miR-892a, miR-892b, miR-891a, miR-891b belonging to the same epididymis-enriched cluster located on the X chromosome, are significantly more expressed in the corpus and cauda regions than in the caput. Interestingly, a strong negative correlation (r = −0,89, P-value≤0.001) was found between the pattern of expression of miR-892b and its potential mRNA target Esrrg (Estrogen Related Receptor Gamma) and with miR-145 and Cldn10 mRNA (r = −0,92, P-value≤0.001). We confirmed that miR-145 and miR-892b inhibit the expression of the luciferase reporter via Cldn10 and Esrrg 3′ UTRs, respectively.ConclusionOur study shows that the expression of miRNAs is segmented along the human epididymis and correlates with the pattern of target gene expression in different regions. Therefore, epididymal miRNAs may be in control of the maintenance of gene expression profile in the epididymis, which dictates segment-specific secretion of proteins and establishes physiological compartments that directly or indirectly affect sperm maturation and fertility.

miR-888 is an expressed prostatic secretions-derived microRNA that promotes prostate cell growth and migration

“…The miR-888 cluster was initially identified via small RNA sequencing in human epididymis tissue, an organ important for male fertility. 40,42,66 miR-888 is expressed consistently throughout the human epididymis, unlike its clustered members miR-890/892a/892b/891a/891b, which are expressed more robustly in the corpus and cauda regions of this organ. 42 These findings imply a role for the miR-888 cluster in the development and/or physiology of the epididymis.…”

“…miR-888 is a conserved member of the miR-743 family with no characterized function. This miRNA resides within a genomic cluster consisting of 7 miRNAs on human chromosome Xq27.3 that were initially classified as epididymisspecific genes [40][41][42] (Fig. 1A).…”

A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

“…They are expressed in various testicular cell populations as well as epididymis, indicating a critical role in the various steps of the highly organized process of spermatogenesis, sperm maturation and maintenance of male fertility. More than 200 miRNAs have also been identified in the human epididymis and this could suggest their potential involvement in regulating the physiological functions of sperm maturation and morphogenesis [181]. Members of the miR-888 cluster (miR-890, miR-891a, miR-891b, miR-892a and miR-892b) are significantly more abundant in the corpus/cauda regions of the epididymis, indicative of a prominent role of the miR-888 cluster in regulating physiological functions of the human epididymis.…”

Identifying functional cancer-specific miRNA–mRNA interactions in testicular germ cell tumor

“…Specifically,

hsa-miR-892b is member of miR-888 gene family that has restricted expression in adult testicular germ cells. They are known as Cancer-testis (CT) antigens which are clustered near the end of the long arm of the X chromosome (Xq27-Xq28) and contain several reported miRNAs like hsa-miR-888, hsa-miR-890, hsa-miR-891a, hsa-miR-891b, hsa-miR-892a, and hsa-miR-892b [68–70];

hsa-miR23a and hsa-miR-23b are involved in epididymal maturation of sperm and express in epididymides [71]; hsa-miR-33 *—including both hsa-miR-33a and hsa-miR-33b —has been shown to be differentially expressed in testes [72]; moreover, according to [73] hsa-miR-33a-5p directly targets EEF1A1; hsa-miR-148a and hsa-miR-148b have been found to affect the modification of susceptibility to oligozoospermia [74];by comparing fertile and infertile populations of men hsa-miR-152-3p has been found to be correlated with sperm concentration [75]; miR-181b and miR-181c were found up-regulated in adult in mouse testis tissue [76], and are involved in transcriptional regulation in haploid germ cells by targeting rsbn1, a gene postulated to be involved in transcriptional regulation in haploid germ cells; miR-155 and miR-146a have been found to be present in male serum [77] and to be correlated with each other; however, while miR-155 is associated with male sub-fertility independent of Low-Grade Systemic Inflammation (LGSI) or androgens, miR-146a is only weakly associated with sub-fertility and LGSI;by comparing miRNA expression patterns for abnormal semen from infertile males and normal semen from healthy males, hsa-miR-130a has been found to be significantly under-expressed in the abnormal semen compared with the normal semen [78]. …”