Differential expression of miR-23a/b-3p and its target genes in male patients with subfertility

Abstract

Objective: To elucidate the potential regulatory function of miR-23a/b-3p on spermatogenesis-specific genes. Design: Reverse transcription quantitative polymerase chain reaction (RT-qPCR) validation, Northern blot, dual luciferase assay, and Western blot confirmation. Setting: University research and clinical institutes. Patient(s): A total of 115 men presenting at an infertility clinic. Intervention(s): None. Main Outcome Measure(s): Significant higher abundance levels of miR-23a/b-3p and lower abundance levels of PFKFB4, HMMR, SPATA6, and TEX15 in oligoasthenozoospermic men compared with those in normozoospermic men. Result(s): In oligoasthenozoospermic men, the abundance levels of miR-23a/b-3p were significantly higher when compared with controls as determined by RT-qPCR. After in silico prediction of potential targets of miR-23a/b-3p, PFKFB4, HMMR, SPATA6, and TEX15 have been identified as direct targets by dual luciferase assays. Mutations in the miR-23a/b-3p binding site within the 3 0 UTRs resulted in abrogated responsiveness to miR-23a/b-3p. PFKFB4, HMMR, SPATA6, and TEX15 mRNA and HMMR and SPATA6 protein levels were significantly lower in oligoasthenozoospermic men compared with in normozoospermic men. Correlation analysis showed that the sperm count, motility, and morphology were negatively correlated with miR-23a/b-3p and positively correlated with PFKFB4, HMMR, SPATA6, and TEX15 abundance levels (lower DCt, the higher abundance levels). Conclusion(s): This study establishes a link between up-regulation of miR-23a/b-3p and the coincident down-regulation of four expressed genes in the sperm of men with oligoasthenozoospermia, compared with men with normozoospermia. This study provides a novel insight into some of the mechanisms leading to male subfertility, offering a possible therapeutic target for treatment, or even for male contraception. (Fertil Steril Ò 2019;112:323-35. Ó2019 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

A systems biology framework integrating GWAS and RNA-seq to shed light on the molecular basis of sperm quality in swine

“…Several miRNAs of interest including miR-23a, miR-27a and miR-122 correlated with seven, eight and eight semen quality traits, respectively (see Additional file 9 : Table S7). miR-23a, is dysregulated in subfertile men [ 92 ], abundance of miR-27a in spermatozoa is associated with lower progressive motility and normal morphology [ 93 ], and expression of miR-122 is associated with abnormal sperm development [ 94 ] and dysregulated in subfertile men [ 95 ].…”

MicroRNA signature in spermatozoa and seminal plasma of proven fertile men and in testicular tissue of men with obstructive azoospermia

“…Additionally, miR‐449a and miR‐199a‐3p were highly expressed in cryptorchid testicle tissues (TANG et al, ). The miR‐23 family (miR‐23a, miR‐23b and miR‐23c) was highly deregulated in spermatozoa, seminal plasma‐derived exosomes and testicular tissue of subfertile men compared with fertile men (Abu‐Halima et al, , , ; Abu‐Halima, Backes, et al, ). More recently, the miR‐23 family was found to be highly expressed in the spermatozoa and testicular tissue of patients with different spermatogenic and testicular impairments.…”

“…The miR‐23 family targets many spermatogenesis‐specific genes like PFKFB4, HMMR, SPATA6 and TEX15. These genes have been identified to be involved in the spermatogenesis process of male infertility (Abu‐Halima et al, ).…”

“…In mammalian spermatogenesis, evidence indicates that even a slight alteration in miRNA expression activities can be detrimental to germ cell function, ultimately leading to impaired spermatogenesis and compromised fertility (Chang et al, ; Hayashi et al, ; Maatouk, Loveland, McManus, Moore, & Harfe, ). Altered expression of miRNAs in men with reduced fertility has been investigated (Abu‐Halima et al, , , ; Abu‐Halima, Backes, et al, ; Abu‐Halima, Hammadeh, et al, ). Specifically, differentially expressed miRNAs were reported in spermatozoa of infertile men with normozoospermic versus.…”

An integrative systems biology approach to identify the molecular basis of sperm quality in swine

“…Several miRNAs of interest including miR-23a, miR-27a and miR-122 correlated with 7, 8 and 8 semen quality traits, respectively (Additional file 7). miR-23a, has been found to be dysregulated in men's subfertility (Abu-Halima et al, 2019). miR-27a…”