A Two-Cohort RNA-seq Study Reveals Changes in Endometrial and Blood miRNome in Fertile and Infertile Women
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AuthorRekker, Kadri; Altmae, Signe; Suhorutshenko, Marina; Peters, Maire; Martinez-Blanch, Juan F.; Codoñer, Francisco M.; Vilella, Felipe; Simón, Carlos; Salumets, Andres; Velthut-Meikas, Agne
Endometrial receptivityInfertilityMicroRNARecurrent implantation failureSmall RNA-seq
Rekker, K. [et al.]. A Two-Cohort RNA-seq Study Reveals Changes in Endometrial and Blood miRNome in Fertile and Infertile Women. Genes 2018, 9, 574; doi:10.3390/genes9120574.
SponsorshipThis research was funded by Estonian Ministry of Education and Research (grant IUT34-16); Enterprise Estonia (grant EU48695); the EU-FP7 Eurostars program (grant NOTED, EU41564); the EU-FP7 Marie Curie Industry-Academia Partnerships and Pathways (IAPP, grant SARM, EU324509); Horizon 2020 innovation programme (WIDENLIFE, 692065); grant from the University of Granada (Incorporación de jóvenes doctores) and grant from the Spanish Ministry of Economy, Industry and Competitiveness–MINECO–(RYC-2016-21199 and grant ENDORE SAF2017-87526).
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.