Fenvalerate-induced Ca transients via both intracellular and extracellular way in mouse GC-2spd (ts) cells

Fenvalerate (Fen) is a widely used synthetic pyrethroid insecticide which is considered to impede the male reproductive function. However, little is known about its underlying mechanism. In this study, we found that fenvalerate affected the Ca²⁺ homeostasis, inducing Ca²⁺ transients via both intracellular Ca²⁺ release and extracellular Ca²⁺ influx. Ca²⁺ influx was via store-operated channel (SOC). Therefore, the effects of fenvalerate on Ryanodine receptors (RyRs) and Inositol (1,4,5)-trisphosphate receptors (IP₃Rs) which involved in forming Ca²⁺ transient was assessed by pharmacological way. We also demonstrated that fenvalerate affected the expression of both receptors and hindered cell proliferation as well. In addition, we discovered that 2-APB, an antagonist of IP₃Rs, inhibited GC-2spd (ts) cells (GC-2 cells) proliferation. Cell cycle analysis of GC-2 cells treated with fenvalerate and 2-APB indicated that both of which showed a slight S-phase accumulation. In conclusion, our results demonstrate that fenvalerate-induced Ca²⁺ transients from both calcium release through RyRs or IP₃Rs and calcium influx via SOC. IP₃Rs seem to serve a predominant role in triggering Ca²⁺ transients which could participate to the regulation of GC-2 cell proliferation.