Dysregulation of an X-linked primate-specific epididymal microRNA cluster in unexplained asthenozoospermia

Abstract

Asthenoszoopermia, characterized by reduced sperm motility, is one of the primary forms of male infertility. Whereas most cases were diagnosed into unexplained asthenozoospermia (UA) because the etiology cannot be identified. In animal models, epigenetic dysregulation in epididymis can impair sperm maturation and result in asthenozoospermia. However, researches of epididymal epigenetic regulation on humans are impeded by the difficulty in obtaining epididymal tissues. We previously identified cell-free seminal microRNAs predominately derived from epididymis in human ejaculate. In the present study, these microRNAs were used to screen and validate the microRNA dysregulation in men with UA, which were divided into screening set and validation set. The expression of five miRNAs (miR-891b, miR-892b, miR-892a, miR-888 and miR-890) was found and confirmed to be dysregulated in men with UA. Interestingly, these five miRNAs belong to a primate-specific miRNA cluster located on the X chromosome with epididymis specific expression. Moreover, obvious coherent dysregulation of these miRNAs were observed in 13% men with UA. Regression analysis demonstrated that levels of these miRNAs were significantly correlated with progressive sperm motility. Functions and pathways of predicted target genes of this cluster suggested its role in sperm maturation. Dysregulation of this miRNA cluster might be an epigenetic basis for some patients with UA. We also showed a noninvasive and feasible approach to get epigenetic information of human epididymis.

A micro RNA cluster in the Fragile‐X region expressed during spermatogenesis targets FMR 1

“…Given that germ cells are in direct contact with SCs [64], this supports a model in which miR-743b-3p and miR-878 regulate gene expression in SCs to influence germ cell differentiation. In support of the possibility that the Fx-mir cluster is important for spermatogenesis, a recent study reported that several human FX-MIR family members-including miR-891b, miR-892b, miR-892a, miR-888, and miR-890-are dysregulated in men with asthenozoospermia [65].…”

MiR‐4485‐3p expression reduced in spermatozoa of men with idiopathic asthenozoospermia

“…In trying to unravel the molecular mechanisms of idiopathic AZS, recent studies have demonstrated dysregulation of miRNAs in total semen (Liu, Cheng, Gao, Wang, & Liu, ; Tian et al, ) seminal plasma (Qing et al, ; Wang et al, ; Zhou, Wang, et al, ; Zhou et al, ) and spermatozoa (Abu‐Halima et al, ; Salas‐Huetos et al, ; Zhou, Zhou, et al, ; Zhou et al, ) of AZS men. Dysregulation of miRNAs may arise from numerous mechanisms containing polymorphisms and/or mutation in these noncoding RNA (Lu et al, ), and also, these dysregulated miRNAs may enact through various mechanisms in molecular pathology of AZS.…”

MicroRNA profiling in spermatozoa of men with unexplained asthenozoospermia

“…Dysregulation of miRNAs is probable to play an important role in male infertility (Khazaie & Nasr Esfahani, ). Previous studies demonstrated altered miRNAs in total semen (Tian et al, ), seminal plasma (Qing et al, ; Wang et al, ; Zhou, Wang, et al, ) and spermatozoa (Abu‐Halima et al, ; Salas‐Huetos et al, ; Zhou et al, ; Zhou et al, ) of AZS men. In line with these studies, it was intended to evaluate the miRNA expression profile in spermatozoa of unexplained AZS men.…”