Abstract
During folliculogenesis, cumulus cells surrounding the oocyte differentiate into corona radiata cells (CRCs) and cumulus oophorus cells (COCs), which are involved in gonadal steroidogenesis and the development of germ cells. Several studies suggested that microRNAs (miRNAs) play an important regulatory role at the post-transcriptional level in cumulus cells. However, comparative miRNA profiles and associated processes in human CRCs and COCs have not been reported before. In this study, miRNA profiles were obtained from CRCs and COCs using next generation sequencing in women undergoing controlled ovarian stimulation for IVF. A total of 785 and 799 annotated miRNAs were identified in CRCs and COCs, while high expression levels of six novel miRNAs were detected both in CRCs and in COCs. In addition, different expression patterns in CRCs and COCs were detected in 72 annotated miRNAs. To confirm the miRNA profile in COCs and CRCs, quantitative real-time PCR was used to validate the expression of annotated miRNAs, differentially expressed miRNAs, and novel miRNAs. The miRNAs in the let-7 family were found to be involved in the regulation of a broad range of biological processes in both cumulus cell populations, which was accompanied by a large amount of miRNA editing. Bioinformatics analysis showed that amino acid and energy metabolism were targeted significantly by miRNAs that were differentially expressed between CRCs and COCs. Our work extends the current knowledge of the regulatory role of miRNAs and their targeted pathways in folliculogenesis, and provides novel candidates for molecular biomarkers in the research of female infertility.
Highlights
Ovarian follicles, which are a densely packed shell of granulosa cells that contain an immature or mature oocyte, are responsible for the development, maturation, and release of a mature egg for fertilisation
Dysfunctional granulosa cells are associated with abnormal folliculogenesis, e.g., polycystic ovary syndrome (PCOS)
An increased number of reports have indicated that ovarian granulosa cells are strictly regulated post-transcriptionally, while small RNAs are the key regulators at this level [11,12,13,14,15,16,17]
Summary
Ovarian follicles, which are a densely packed shell of granulosa cells that contain an immature or mature oocyte, are responsible for the development, maturation, and release of a mature egg for fertilisation. They are responsible for synthesising and secreting hormones that are essential for follicular development, the maintenance of the reproductive tract and menstrual cycle, and the development of female secondary sex characteristics [1]. CRCs are connected to the oocyte via transzonal cytoplasmic projections until ovulation. The close interactive and mutual relationship between the oocyte, CRCs and COCs supports the follicular development and maturation of oocytes via sterol
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