Identification of circulating small non-coding RNAs in relation to male subfertility and reproductive hormones.

Autor: Kumar K; Molecular Reproductive Medicine, Department of Translational Medicine, Lund University, Malmö, Sweden; Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark; International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Denmark., Trzybulska D; Molecular Reproductive Medicine, Department of Translational Medicine, Lund University, Malmö, Sweden., Tsatsanis C; Molecular Reproductive Medicine, Department of Translational Medicine, Lund University, Malmö, Sweden; Department of Clinical Chemistry, School of Medicine, University of Crete, Heraklion, Greece., Giwercman A; Molecular Reproductive Medicine, Department of Translational Medicine, Lund University, Malmö, Sweden; Reproductive Medicine Centre, Skåne University Hospital, Malmö, Sweden., Almstrup K; Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Denmark; International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Denmark. Electronic address: kristian.almstrup@regionh.dk.
Jazyk: angličtina
Zdroj: Molecular and cellular endocrinology [Mol Cell Endocrinol] 2019 Jul 15; Vol. 492, pp. 110443. Date of Electronic Publication: 2019 May 08.
DOI: 10.1016/j.mce.2019.05.002
Abstrakt: 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.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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