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Background: Fibroblast growth factors (FGFs) are growth factors that have diverse biological activities including broad mitogenic and cell survival activities. They function through the activation of a specific tyrosine kinase receptor that transduces the signal by activating several intracellular signaling pathways. Objective: To identify the different signaling pathways involved in the mechanism of action of FGF8 and FGF18 on ovine granulosa cells using mass spectrometry. Materials and Methods: Ovine ovarian granulosa cells were harvested from adult sheep independently at the stage of the estrous cycle and were cultured at a density of 500,000 viable cells in 1 ml DMEM/F12 medium for five days. The cells were then treated on day 5 of culture with 10 ng/mL FGF8 and FGF18 for 30 minutes, and total cell protein was collected for mass spectrometry. Results: Mass spectrometry showed that both FGF8 and FGF18 significantly induce simultaneous upregulation of several proteins, including ATF1, STAT3, MAPK1, MAPK3, MAPK14, PLCG1, PLCG2, PKCA, PIK3CA, RAF1, GAB1, and BAG2 (> 1.5-fold; p < 0.01). Conclusion: ATF1 and STAT3 are important transcription factors involved in cell growth, proliferation and survival, and consequently can hamper or rescue the normal ovine reproductive system function.

Granulosa cells exposed to fibroblast growth factor 8 and 18 reveal early onset of cell growth and survival