Fenvalerate-induced Ca2+ 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.