Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Male subfertility is often associated with sub-optimal health status and traditional semen and hormone analysis reveal only limited information about the reduced fertility potential. Circulating small non-coding RNAs (sncRNAs) are paracrine and endocrine messengers, with prognostic potential. Here, we utilised small RNA-Seq to identify novel cell-free circulating sncRNAs that could act as potential biomarkers of male subfertility. We analysed sera from twelve subfertile men and four controls. The subfertile men were further sub-divided into the three groups based on reproductive hormone levels: group 1 (n = 4): hormone levels similar to the controls, group 2 (n = 4) showing elevated FSH levels, and group 3 (n = 4) with low total testosterone (TT). Total RNA was extracted from serum and sequenced to identify miRNAs and piRNAs. Selected sncRNAs were qPCR validated in a larger and independent cohort of subfertile men (n = 57) and normozoospermic controls (n = 19). RNA-Seq resulted in the identification of 1123 and 330 circulating miRNAs and piRNAs, respectively. Several miRNAs and piRNAs were differentially (p = 0.05) present between controls and subfertile men. Subfertile men with low TT appeared to have a distinct sncRNA profile, compared to group 1 and 2. Validation of two miRNAs (hsa-miR-542-5p and hsa-let-7i-3p) and one piRNA (hsa-piR-26399) in an independent cohort confirmed a significant difference in circulating levels between subfertile and control men. Enrichment analysis of the putative miRNA targets showed association with steroid biosynthesis pathway highlighting a potential regulatory role of these miRNAs. We propose that circulating sncRNAs may represent new important functional biomarkers in male reproductive endocrinology.

Original publication




Journal article


Molecular and Cellular Endocrinology

Publication Date