Seminal plasma microRNAs: potential biomarkers for spermatogenesis status

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs (18-25 nt), playing important regulatory roles via interaction with cellular messenger RNAs. The altered expression of miRNAs in specific tissues has been associated with diseases such as cancer and diabetes. We examined the presence of two selected miRNAs (miR-19b and let-7a) in human seminal plasma from fertile men and idiopathic infertile patients with oligozoospermia and non-obstructive azoospermia (NOA) using quantitative real-time PCR. We detected miRNAs in the seminal plasma of humans. The levels of miRNAs in the seminal plasma were reproducible in repeat samples from the same individuals. In addition, we examined the expression patterns of two selected miRNAs in 96 idiopathic infertile males (48 oligozoospermia and 48 NOA) and 48 fertile controls. Another 48 individuals of each group were used for verification. Our data showed that the expression levels of these two miRNAs in the seminal plasma significantly increased in idiopathic infertile males with NOA compared with fertile controls, whereas the expression levels were similar between idiopathic infertile males with oligozoospermia and fertile controls. In conclusion our results indicate that the expression of miR-19b and let-7a in the seminal plasma are reproducible and stable. Aberrant over-expression levels of miR-19b and let-7a may be an indicator of spermatogenic failure.

Comparative profiling of small RNAs of pig seminal plasma and ejaculated and epididymal sperm

“…miR-34c, which is also present in humans, mice and bull sperm (Amanai et al 2006, Krawetz et al 2011, Stowe et al 2014, was detected in all the three libraries from pig ejaculated sperm, epididymal sperm and seminal plasma, indicating that this miRNA species is highly conserved across mammals and confirming that it plays a significant biological role in spermatogenesis or in early embryonic development. We also found that three miRNAs (ssc-let-7a, ssc-miR26a and ssc-miR-10b) were shared in the top 10 most abundant miRNAs in the three libraries, and one of them (miR-let-7a) was detected in mouse epididymal sperm and human seminal plasma (Liu et al 2012a, Wu et al 2012, Cheong et al 2014) and shown to be involved in the regulation of embryo implantation in mice (Liu et al 2012a, Cheong et al 2014). Furthermore, the expression level of let-7a in human seminal plasma was significantly associated with male infertility (Wu et al 2012).…”

“…We also found that three miRNAs (ssc-let-7a, ssc-miR26a and ssc-miR-10b) were shared in the top 10 most abundant miRNAs in the three libraries, and one of them (miR-let-7a) was detected in mouse epididymal sperm and human seminal plasma (Liu et al 2012a, Wu et al 2012, Cheong et al 2014) and shown to be involved in the regulation of embryo implantation in mice (Liu et al 2012a, Cheong et al 2014). Furthermore, the expression level of let-7a in human seminal plasma was significantly associated with male infertility (Wu et al 2012). Studies have shown that both miR-26a and miR10b, which are also present in mouse and bull sperms (Amanai et al 2006, Bissonnette et al 2009), appear to be associated with carcinogenesis (Ma et al 2007, Kato et al 2015, but their role in spermatogenesis and in early embryonic development remains unknown.…”

“…The seminal plasma is a mixture of fluids secreted by the sexual glands (seminal vesicles, the prostate and the bulbourethral glands) and other male sexual organs (testis and epididymis) and provides a nutritive and protective medium for sperm after ejaculation (Juyena & Stelletta 2012). The presence of RNA molecules in human seminal plasma was first identified by Huang and coworkers (Huang et al 2009), and then confirmed by several studies (Huang et al 2009, Weber et al 2010, Wu et al 2012, Xiong 2014. In seminal plasma, these RNA molecules display remarkable stability and resistance to degradation, possibly because of their association with protein complexes or because they are enclosed within membrane-bound nanovesicles referred to as 'exosomes' that are produced by the diverse sexual glands and organs (Sullivan et al 2005, Piehl et al 2013.…”

“…Therefore, it is impossible to compare RNA profiles between ejaculated sperm and epididymal sperm in the same species (humans or mice). Seminal plasma is also relatively easy to collect in humans than that in mice, and several RNA species have been identified within seminal plasma (Wu et al 2012, Xiong 2014, Hong et al 2016. However, comparatively little is known about the distribution of RNAs in epididymal sperm, seminal plasma and ejaculated sperm.…”

Molecular analysis of testis biopsy and semen pellet as complementary methods with histopathological analysis of testis in non-obstructive azoospermia

“…In addition, Wu and his colleagues showed that seminal plasma microRNAs can be regarded as potential biomarkers for the evaluation of spermatogenesis. The miR19b and let-7a miRNAs have shown aberrant over-expression in the seminal plasma of men with idiopathic NOA compared with fertile controls that may be an indicator of spermatogenic failure [28].…”