FGF21 Promotes Proliferation and Estradiol Synthesis in Porcine Granulosa Cells

Background: The proliferation and estradiol synthesis in granulosa cells (GCs) directly promotes follicular development. Previous studies had found that FGF21 regulated the hypothalamic-pituitary-gonad axis in response to the control of fertility. However, the functions and mechanisms of FGF21 in GCs are unclear. Results: : Here, we found that the mRNA and protein levels of FGF21 in the ovarian tissue of high-yielding sows ( Sus scrofa ) was higher than that in low-yielding sows. Moreover, FGF21 was predominantly expressed in porcine GCs. Additionally, ELISA assay showed estradiol was significantly increased when overexpression of FGF21 in porcine GCs. Meanwhile, overexpressed FGF21 up-regulated both the mRNA and protein levels of key estradiol synthesis-related genes in porcine GCs, including StAR , CYP11A1 and CYP19A1 . Corresponsingly, knockdown FGF21 inhibited estradiol levels and its synthesis-related genes expression. Besides, overexpression of FGF21 promoted the proliferation of porcine GCs, displayed as increasing the percentage of S-phase cells in cell cycle and EdU positive cells, including cell viability, and upregulated cell cycle genes, including cell cycle protein B (Cyclin B) and protein E (Cyclin E). Corresponsingly, knockdown FGF21 in porcine GCs suppressed the cell cycle and cell viability, as well as EdU positive cell number. Conclusions: : These findings highlight that FGF21 is associated with the development of GCs and may be a novel underlying regulator of porcine follicular development.