Using Small Non-Coding RNAs in Extracellular Vesicles of Semen as Biomarkers of Male Reproductive System Health: Opportunities and Challenges

Abstract

Reproductive dysfunction and urogenital malignancies represent a serious health concern in men. This is in part as a result of the absence of reliable non-invasive tests of diagnosis/prognosis. Optimizing diagnosis and predicting the patient’s prognosis will affect the choice of the most appropriate treatment and therefore increase the chances of success and the result of therapy, that is, it will lead to a more personalized treatment of the patient. This review aims firstly to critically summarize the current knowledge of the reproductive roles played by extracellular vesicle small RNA components, which are typically altered in diseases affecting the male reproductive tract. Secondly, it aims to describe the use of semen extracellular vesicles as a non-invasive source of sncRNA-based biomarkers for urogenital diseases.

Extracellular vesicles as carriers of mRNA: Opportunities and challenges in diagnosis and treatment

“…Important to consider though, are unique microbiomes that colonize the vaginal and gastrointestinal environments, which may make isolation of host-derived EVs difficult. Seminal fluid has high concentrations of EVs, and has been utilized for investigations into both male fertility and prostate cancer 97 , 98 . It is important to consider differences in EVs isolated from different biofluids.…”

Small Non-Coding RNAs in Male Reproduction

“…155 sncRNA composition of the seminal fluid is likely to reflect the spermatogenic activity in the testis, and, therefore, seminal plasma sncRNA analysis is considered as a promising approach for the diagnosis of male infertility. 7 For the diagnosis of azoospermia (the absence of sperm in the ejaculate), the seminal plasma sncRNA analysis provides a potential tool to differentiate between nonobstructive azoospermia due to spermatogenesis failure and obstructive azoospermia, the latter being characterized by full testicular spermatogenesis and high likelihood to obtain sperm for MAR treatment using testicular biopsy. Testicular sperm retrieval is also used as a treatment of nonobstructive azoospermia, and in these cases, seminal plasma sncRNA analysis could predict the success of sperm retrieval, which is greatly dependent on the type of spermatogenic defect.…”

“…Some studies have indeed revealed that semen extracellular sncRNA content (including miRNAs, piRNAs, tsRNAs) can be used to predict the presence of sperm in testicular tissue and the success of testicular sperm retrieval in nonobstructive azoospermia patients. 7,[156][157][158][159]…”

“…6 Considering the association of aberrant expression of sncRNAs with abnormal sperm production, sncRNAs have clinical relevance as potential indicators or biomarkers of male subfertility/infertility and other disorders of male reproductive health. 7 8 In addition, cumulative evidence shows that sperm sncRNAs can transmit epigenetic information on father's acquired conditions such as metabolic or psychiatric disorders to the offspring; therefore, they not only contribute to male reproductive health but also play a role in the health of the offspring. 9 This further highlights the significance of understanding sncRNA functions in the germline to improve human health.…”

“…6 Considering the association of aberrant expression of sncRNAs with abnormal sperm production, sncRNAs have clinical relevance as potential indicators or biomarkers of male subfertility/infertility and other disorders of male reproductive health. 7,8 In addition, cumulative Keywords ► small non-coding RNA ► miRNA ► piRNA ► male germline ► sperm ► fertility…”