Podophyllotoxin affects porcine oocyte maturation by inducing oxidative stress-mediated early apoptosis

Abstract

Podophyllotoxin (PPT) is a lignan extracted from podophyllum genera and it shows potent antitumor activity since it could effectively inhibit the assembly of microtubule in tumor cells. However, the effects of podophyllotoxin exposure on porcine oocyte quality is still unclear. In present study we tried to examine whether podophyllotoxin exposure was toxic to porcine oocyte maturation. Our results showed that podophyllotoxin exposure inhibited porcine oocyte maturation, showing with the failure of polar body extrusion, and the inhibitory effects of podophyllotoxin on porcine oocytes was dose-depended. Moreover, the meiotic spindle formation was disturbed and the chromosomes were misaligned in the podophyllotoxin-treated porcine oocytes. However, there was no different expression for p-MAPK and ace-tubulin between the control and podophyllotoxin treatment group. In addition, after 0.01 μM podophyllotoxin treatment, the intracellular reactive oxygen species (ROS) levels and the Annexin-V signal at MI stage significantly increased compared to the control group, indicating the occurrence of oxidative stress and early apoptosis. Taken together, our results suggested that the toxic effects of podophyllotoxin exposure on porcine oocyte maturation might be through its effects on spindle formation and the induction of oxidative stress-mediated early apoptosis.

Keywords: Apoptosis; Meiosis; Oocyte; Podophyllotoxin; ROS.