期刊
THERIOGENOLOGY
卷 194, 期 -, 页码 1-12出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.theriogenology.2022.09.020
关键词
FGF21; Granulosa cells; PI3K/AKT; Proliferation; Estradiol; Pig
资金
- National Natural Science Foundation of China [32272849]
- National Key R&D Program of China [2021YFF1000602]
- China Agriculture Research System of MOF and MARA
The research found that fibroblast growth factor 21 (FGF21) promotes the proliferation and estradiol (E2) synthesis in porcine ovarian granulosa cells (GCs) by activating signaling pathways.
The proliferation and steroidogenesis of mammalian ovarian granulosa cells (GCs) are related to follicular development. Previous studies found that fibroblast growth factor 21 (FGF21) regulated female fertility through the hypothalamicepituitaryegonad axis. However, FGF21 receptors are expressed on GCs, so we speculate that it might affect female reproduction by regulating their physiological activities. Here, we showed that FGF21, fibroblast growth factor receptor-1(FGFR1), and beta-klotho (KLB) were expressed in porcine GCs. ELISA assays showed that estradiol (E2) production was increased significantly when treating GCs with recombinant FGF21 (rFGF21). In addition, rFGF21 upregulated the mRNA and protein levels of E2 synthesis-related genes including StAR, CYP11A1, and CYP19A1 in porcine GCs. Correspondingly, FGF21 siRNA inhibited E2 levels and its synthesis-related gene expression. After rFGF21 treatment, CCK8 showed increased cell viability, and flow cytometry showed that the number of S phase increased, and cycle-related genes also increased. However, treatment with FGF21 siRNA to porcine GCs suppressed the cell cycle, viability, and EdU positive cell number. Consequently, FGF21/FGFR1/KLB forms a complex to activate the phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR signaling pathway and further promote the proliferation and E2 synthesis in porcine GCs. Collectively, these findings suggests that FGF21 regulates porcine ovarian folliculogenesis.
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