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Open AccessArticle

A Two-Cohort RNA-seq Study Reveals Changes in Endometrial and Blood miRNome in Fertile and Infertile Women

Institute of Clinical Medicine, Department of Obstetrics and Gynecology, University of Tartu, 50406 Tartu, Estonia
Competence Centre on Health Technologies, 50410 Tartu, Estonia
Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Granada, 18071 Granada, Spain
Lifesequencing SL, 46980 Valencia, Spain
Igenomix Foundation/INCLIVA, 46010 Valencia, Spain
Igenomix SL, 46980 Valencia, Spain
Department of Obstetrics and Gynecology, Valencia University, 46010 Valencia, Spain
Institute of Biomedicine and Translational Medicine, Department of Biomedicine, University of Tartu, 50412 Tartu, Estonia
Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, FI-00014 Helsinki, Finland
Department of Chemistry and Biotechnology, Tallinn University of Technology, 12618 Tallinn, Estonia
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Genes 2018, 9(12), 574;
Received: 25 September 2018 / Revised: 7 November 2018 / Accepted: 7 November 2018 / Published: 23 November 2018
(This article belongs to the Special Issue microRNA Regulation in Health and Disease)
The endometrium undergoes extensive changes to prepare for embryo implantation and microRNAs (miRNAs) have been described as playing a significant role in the regulation of endometrial receptivity. However, there is no consensus about the miRNAs involved in mid-secretory endometrial functions. We analysed the complete endometrial miRNome from early secretory (pre-receptive) and mid-secretory (receptive) phases from fertile women and from patients with recurrent implantation failure (RIF) to reveal differentially expressed (DE) miRNAs in the mid-secretory endometrium. Furthermore, we investigated whether the overall changes during early to mid-secretory phase transition and with RIF condition could be reflected in blood miRNA profiles. In total, 116 endometrial and 114 matched blood samples collected from two different population cohorts were subjected to small RNA sequencing. Among fertile women, 91 DE miRNAs were identified in the mid-secretory vs. early secretory endometrium, while no differences were found in the corresponding blood samples. The comparison of mid-secretory phase samples between fertile and infertile women revealed 21 DE miRNAs from the endometrium and one from blood samples. Among discovered novel miRNAs, chr2_4401 was validated and showed up-regulation in the mid-secretory endometrium. Besides novel findings, we confirmed the involvement of miR-30 and miR-200 family members in mid-secretory endometrial functions. View Full-Text
Keywords: endometrial receptivity; infertility; microRNA; recurrent implantation failure; small RNA-seq endometrial receptivity; infertility; microRNA; recurrent implantation failure; small RNA-seq
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Rekker, K.; Altmäe, S.; Suhorutshenko, M.; Peters, M.; Martinez-Blanch, J.F.; Codoñer, F.M.; Vilella, F.; Simón, C.; Salumets, A.; Velthut-Meikas, A. A Two-Cohort RNA-seq Study Reveals Changes in Endometrial and Blood miRNome in Fertile and Infertile Women. Genes 2018, 9, 574.

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