Altered microRNA and Piwi-interacting RNA profiles in cumulus cells from patients with diminished ovarian reserve

Abstract

Diminished ovarian reserve (DOR) is defined as decreased number or quality of follicles and oocytes in a woman at childbearing age. It is estimated that up to 10% of women in the general population may suffer from DOR. This study aims to comprehensively characterize microRNA (miRNA) and Piwi-interacting RNA (piRNA) expression profiles in cumulus cells of DOR patients. Cumulus cells were collected from 20 women of similar chronological age who received assisted reproductive technology treatment: 10 with DOR and 10 with normal ovarian reserve (NOR). The small RNAs were extracted from each sample and reverse transcribed. Deep sequencing and bioinformatic analysis were performed to identify the small noncoding RNA profiles. The rRNAs were the most abundant small RNA class in cumulus cells derived from human MII oocytes, following were miRNAs and tRNAs. Twenty-six piRNAs, 79 annotated miRNAs, and 5 novel miRNAs were identified differentially expressed. In DOR group, the chromosomal strand bias patterns of piRNAs on chromosome 1, 3, 5, and X were distinct from its counterpart in NOR group. The involved biological pathways from the putative target genes of differentially expressed miRNAs were enriched by using GO analysis and KEGG pathway annotations, and mTOR pathway and meiosis-associated biological processes were enriched. This study provided additional information on the dysfunctions of cumulus cells in patients with diminished ovarian reserve. Future investigations will involve the characterization of specific functional roles of noncoding small RNA in ovarian reserve regulation.

Keywords: cumulus cells; deep sequencing; diminished ovarian reserve; miRNAs; piRNAs.