Identification of circulating small non-coding RNAs in relation to male subfertility and reproductive hormones
(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.
(Less)
- author
- Kumar, Kishlay LU ; Trzybulska, Dorota LU ; Tsatsanis, Christos LU ; Giwercman, Aleksander LU and Almstrup, Kristian
- organization
- publishing date
- 2019-05-08
- 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
- article number
- 110443
- publisher
- Elsevier
- external identifiers
-
- scopus:85065515899
- pmid:31077744
- 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
- 2024-05-14 10:19:22
@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>}},
author = {{Kumar, Kishlay and Trzybulska, Dorota and Tsatsanis, Christos and Giwercman, Aleksander and Almstrup, Kristian}},
issn = {{0303-7207}},
keywords = {{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}},
doi = {{10.1016/j.mce.2019.05.002}},
volume = {{492}},
year = {{2019}},
}