MicroRNA-10b suppresses goat granulosa cell proliferation by targeting brain-derived neurotropic factor.

ABSTRACT

Brain-derived neurotropic factor (BDNF) and its high-affinity receptor, tyrosine kinase receptor B, have been assumed to be involved in female reproduction and have recently shown to play an essential role in follicle activation and oocyte maturation. In this study, we analyzed the expression of miR-10b and BDNF in the ovary and discovered that the expression of miR-10b was higher in monotocous goat ovaries than in polytocous goat ovaries, whereas the expression pattern of BDNF in ovary was opposite. Moreover, human chorionic gonadotropin induced rapid and transient expression of BDNF messenger RNA and protein. In contrast, human chorionic gonadotropin upregulated miR-10b expression in a time-dependent manner. The BDNF gene was identified as a direct target of miR-10b using a dual-luciferase reporter assay. Transfection of granulosa cells with miR-10b decreased BDNF messenger RNA and protein levels. MiR-10b overexpression inhibited cell proliferation, whereas BDNF promoted cell proliferation. However, a combined treatment with miR-10b and BDNF promoted cell proliferation, indicating that the reintroduction of BDNF reversed the suppressive effect of miR-10b. These results demonstrate that miR-10b downregulates BDNF expression in granulosa cells by directly targeting the 3' untranslated regions and plays an important role in inhibiting granulosa cell proliferation by targeting BDNF.