A1 Refereed original research article in a scientific journal

Aging and serum exomiR content in women-effects of estrogenic hormone replacement therapy




AuthorsKangas R, Tormakangas T, Fey V, Pursiheimo J, Miinalainen I, Alen M, Kaprio J, Sipila S, Saamanen AM, Kovanen V, Laakkonen EK

PublisherNATURE PUBLISHING GROUP

Publication year2017

JournalScientific Reports

Journal name in sourceSCIENTIFIC REPORTS

Journal acronymSCI REP-UK

Article numberARTN 42702

Volume7

Number of pages14

ISSN2045-2322

DOIhttps://doi.org/10.1038/srep42702

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/19206367


Abstract
Exosomes participate in intercellular messaging by transporting bioactive lipid-, protein-and RNA-molecules and -complexes. The contents of the exosomes reflect the physiological status of an individual making exosomes promising targets for biomarker analyses. In the present study we extracted exosome microRNAs (exomiRs) from serum samples of premenopausal women (n = 8) and monozygotic postmenopausal twins (n = 10 female pairs), discordant for the use of estrogenic hormone replacement therapy (HRT), in order to see whether the age or/and the use of HRT associates with exomiR content. A total of 241 exomiRs were detected by next generation sequencing, 10 showing age, 14 HRT and 10 age + HRT-related differences. When comparing the groups, differentially expressed miRs were predicted to affect cell proliferation processes showing inactivation with younger age and HRT usage. MiR-106-5p, -148a-3p, -27-3p, -126-5p, -28-3p and -30a-5p were significantly associated with serum 17 beta-estradiol. MiRs formed two hierarchical clusters being indicative of positive or negative health outcomes involving associations with body composition, serum 17 beta-estradiol, fat-, glucose-and inflammatory markers. Circulating exomiR clusters, obtained by NGS, could be used as indicators of metabolic and inflammatory status affected by hormonal changes at menopause. Furthermore, the individual effects of HRT-usage could be evaluated based on the serum exomiR signature.

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