The granulosa cells in the mammalian ovarian follicle respond to gonadotropin signalling and are involved in the processes of folliculogenesis and oocyte maturation. Studies on gene expression and regulation in human granulosa cells are of interest due to their potential for estimating the oocyte viability and IVF success. However, the post-transcriptional gene expression studies on microRNA (miRNA) level in the human ovary have been scarce.
The current study determined the miRNA profile by deep sequencing of the two intrafollicular somatic cell types: mural and cumulus granulosa cells (MGC and CGC, respectively) isolated from women undergoing controlled ovarian stimulation and in vitro fertilization. Altogether 936 annotated and nine novel miRNAs were identified. Ninety of the annotated miRNAs were differentially expressed between MGC and CGC. Bioinformatic prediction revealed that TGFβ, ErbB signalling and heparan sulphate biosynthesis were targeted by miRNAs in both granulosa cell populations, while extracellular matrix remodelling, Wnt and neurotrophin signalling pathways were enriched among miRNA targets in MGC. Two of the novel miRNAs found were of intronic origin: one from the aromatase and the other from the FSH receptor gene. The latter miRNA was predicted to target the activin signalling pathway.
In addition to revealing the genome-wide miRNA signature in human granulosa cells, these results suggest that post-transcriptional regulation of gene expression by miRNAs could play an important role in the modification of gonadotropin signalling. miRNA expression studies could therefore lead to new prognostic markers in assisted reproductive technologies.
- Velthut-Meikas A, Simm J, Tuuri T, Tapanainen JS, Metsis M, Salumets A. (2013) Research Resource: Small RNA-seq of human granulosa cells reveals miRNAs in FSHR and aromatase genes. Mol Endocrinol [Epub ahead of print]. [abstract]