The expression of small RNAs in exosomes of follicular fluid altered in human polycystic ovarian syndrome

Abstract

Polycystic ovary syndrome (PCOS) can cause reproductive disorders that may affect oocyte quality from punctured follicles in human follicular fluid (HFF). The non-coding RNA family includes micro RNA (miRNA), piwi-interacting RNA (piRNA) and transfer RNA (tRNA); these non-coding RNA transcripts play diverse functions and are implicated in a variety of diseases and health conditions, including infertility. In this study, to explore the role of HFF exosomes in PCOS, we extracted and sequenced RNA from HFF exosomes of PCOS patients and compared the analysis results with those of non-PCOS control group. The HFF exosomes were successfully isolated and characterized in a variety of ways. The sequencing results of the HFF exosomal RNA showed that about 6.6% of valid reads in the PCOS group and 8.6% in the non-PCOS group were successfully mapped to the human RNA database. Using a hierarchical clustering method, we found there were ten small RNA sequences whose expression was significantly different between the PCOS and non-PCOS groups. We chose six of them to predict target genes of interest for further GO analysis, and pathway analysis showed that the target genes are mainly involved in biosynthesis of amino acids, glycine, serine and glycosaminoglycan, as well as threonine metabolism. Therefore, the small RNA sequences contained in HFF EXs may play a key role in the mechanism that drives PCOS pathogenesis, and thereby can act as molecular biomarkers for PCOS diagnosis in the future.

Roles of Extracellular Vesicles in Human Reproduction

“…The amount of EVs (mainly exosomes) in plasma of patients with PCOS are significantly increased and positively correlated with the number of follicles [73]. The expression of non-coding RNAs altered in exosomes of FF in PCOS, including miRNAs, piRNAs, and tRNAs [74]. Further study found that there is differential expression of miRNAs in plasma exosomes of women with PCOS, which was related to the menstrual cycle, antral follicle count (AFC, means the number of antral follicle) and hormone levels [75].…”

Exosomes as Biomarkers for Female Reproductive Diseases Diagnosis and Therapy

“…These miRNAs were related to pathways of different amino acid metabolism. They also showed that a variety of tRNAs and piwi-interacting RNAs (piRNAs) were differentially expressed in HFF exosomes from PCOS patients [ 66 ]. PiRNAs are small non-coding RNA molecules that are abundant in the germline cells of animals [ 67 ].…”

Tetraspanins, More than Markers of Extracellular Vesicles in Reproduction

“…Later, the uptake of EVs (CD63-positive) by bovine granulosa and cumulus cells was documented, and EVs were identified in cumulus cells and in transzonal projections [ 142 ]. CD63- and CD81-positive exosomes have also been isolated from human FF [ 143 , 144 ]. The impact of EVs on ovarian function was documented for the first time by Hung et al [ 145 ] in cattle.…”