MicroRNAs in spermatogenesis dysfunction and male infertility: clinical phenotypes, mechanisms and potential diagnostic biomarkers

Abstract

Infertility affects approximately 10–15% of couples worldwide who are attempting to conceive, with male infertility accounting for 50% of infertility cases. Male infertility is related to various factors such as hormone imbalance, urogenital diseases, environmental factors, and genetic factors. Owing to its relationship with genetic factors, male infertility cannot be diagnosed through routine examination in most cases, and is clinically called ‘idiopathic male infertility.’ Recent studies have provided evidence that microRNAs (miRNAs) are expressed in a cell-or stage-specific manner during spermatogenesis. This review focuses on the role of miRNAs in male infertility and spermatogenesis. Data were collected from published studies that investigated the effects of miRNAs on spermatogenesis, sperm quality and quantity, fertilization, embryo development, and assisted reproductive technology (ART) outcomes. Based on the findings of these studies, we summarize the targets of miRNAs and the resulting functional effects that occur due to changes in miRNA expression at various stages of spermatogenesis, including undifferentiated and differentiating spermatogonia, spermatocytes, spermatids, and Sertoli cells (SCs). In addition, we discuss potential markers for diagnosing male infertility and predicting the varicocele grade, surgical outcomes, ART outcomes, and sperm retrieval rates in patients with non-obstructive azoospermia (NOA).

Genome and Epigenome Disorders and Male Infertility: Feedback from 15 Years of Clinical and Research Experience

“…Recently, small non-coding RNAs were assessed clinically in the context of male infertility. Some micro-RNAs were suggested to be potential biomarkers for infertility diagnosis as well as for other diseases like varicocele, and predictors of surgical and in vitro fertilization outcomes [ 61 ].…”

Integrative Assessment of Seminal Plasma Biomarkers: A Narrative Review Bridging the Gap between Infertility Research and Clinical Practice

“…Male fertility is adversely affected by varicocele through a number of processes. Sperm concentration, total sperm motility, and good sperm morphology are all positively correlated with low expression of seminal miR-122/-181a/-34c5, which is also linked to greater varicocele grades and bilateral varicocele [ 62 ]. With a negative correlation to both sperm count and seminal inhibin-B, seminal plasma miR-210-3p is a viable biomarker for predicting aberrant semen quality brought on by varicocele [ 57 ].…”

“…Not all NOA patients are able to obtain sperm utilizing micro-TESE. ICSI is a method of choice for successful fertilization in such cases, but positive results are not guaranteed [ 62 ].…”

“…Patients with NOA were found to have higher mean blood plasma levels, which were found to be adversely linked with both left and right testicular size and serum total testosterone. Alternatively explained, the most plausible diagnostic markers for NOA include miR-10b-3p, miR-34b-5p, miR-122, miR-31-5p, miR-141, miR-429, miR-7-1-3p, hsa-miR-34b*, miR-19b, miR-let-7a, miR−192a, miR-34c-5p, miR-146b-5p, miR-181a, miR-374b, miR-509-5p, miR-513a-5p, and miR-20a-5p [ 62 ].…”

“…Sperm hsa-miR-34c-5p is the only noncoding RNA in semen that has a significant predictive value for male idiopathic infertility receiving ICSI cycles, according to one study. In addition, 10 miRNAs in total, including a panel of three, have shown good to exceptional diagnostic potential, particularly for non-obstructive azoospermia and asthenozoospermia [ 62 ]. Several studies documented SP and sperm piRNAs’ diagnostic potential, with findings suggesting a predictive utility for separating sperm quality states [ 80 ].…”