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

Kumar, Kishlay LU ; Trzybulska, Dorota LU ; Tsatsanis, Christos LU ; Giwercman, Aleksander LU and Almstrup, Kristian (2019) In Molecular and Cellular Endocrinology 492.
Abstract

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... (More)

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.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Male subfertility, miRNAs, piRNAs, Reproductive endocrinology, Sequencing, Small RNAs
in
Molecular and Cellular Endocrinology
volume
492
publisher
Elsevier
external identifiers
  • scopus:85065515899
ISSN
0303-7207
DOI
10.1016/j.mce.2019.05.002
language
English
LU publication?
yes
id
8817f199-95db-4f6f-a285-f8df2b508a23
date added to LUP
2019-05-21 21:12:23
date last changed
2019-07-01 11:53:49
@article{8817f199-95db-4f6f-a285-f8df2b508a23,
  abstract     = {<p>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.</p>},
  articleno    = {110443},
  author       = {Kumar, Kishlay and Trzybulska, Dorota and Tsatsanis, Christos and Giwercman, Aleksander and Almstrup, Kristian},
  issn         = {0303-7207},
  keyword      = {Male subfertility,miRNAs,piRNAs,Reproductive endocrinology,Sequencing,Small RNAs},
  language     = {eng},
  month        = {05},
  publisher    = {Elsevier},
  series       = {Molecular and Cellular Endocrinology},
  title        = {Identification of circulating small non-coding RNAs in relation to male subfertility and reproductive hormones},
  url          = {http://dx.doi.org/10.1016/j.mce.2019.05.002},
  volume       = {492},
  year         = {2019},
}