Okadaic Acid Inhibits Protein Phosphatases to Suppress Spermatogonial Cell Proliferation

Abstract Okadaic acid (OA) is a marine toxin which inhibits protein phosphatases. Its toxicities in several tissues have been well established, but the influence of exposure to low OA concentrations in male reproductive system is poorly understood. Here we aimed to explore the potential reproductive toxicity of OA and the mechanism behind it. The GC-1 cells were exposed to OA, and the changes of proliferation rates were detected. TUNEL assay was also conducted to determine the GC-1 cell apoptosis. Effects of OA on cytoskeleton and cyclin expression were investigated by fluorescein conjugated phalloidin. Potential molecular regulation on proliferation was analyzed based on transcriptomic analysis. OA inhibited the proliferation of GC-1 cells apparently with loss of cell-cell junctions and focal aggregated around the cells. The cyclin D/E mRNA and protein levels significantly decreased and the phosphorylation of ERK1/2 was blocked concordantly in OA treated cells. PPI network analysis pointed out ERK1 as a key node of responsive gene to the injury. In conclusion, OA shows apparent cytotoxicity on spermatogonial cells of male reproductive system and the cytotoxicity present was revealed by affecting the activation of ERK1/2 MAPK pathway which hinders the cyclin expression and actin stress fiber formation further.