ROS-independent cytotoxicity of 9,10-phenanthrenequinone inhibits cell cycle progression and spindle assembly during meiotic maturation in mouse oocytes

Abstract

Diesel exhaust particles (DEPs) are major components of ambient particulate matter and are associated with various adverse health effects. Typically, DEPs contain a vast number of organic compounds, among which 9,10-phenanthrenequinone (9,10-PQ), the quinone derivative of the polycyclic aromatic hydrocarbon phenanthrene, is one of the most abundant and toxic. 9,10-PQ can produce excessive reactive oxygen species (ROS) via redox cycling and exhibit cytotoxicity in various cells. However, the underlying mechanisms involved in cytotoxicity of 9,10-PQ remain elusive. In this study, we investigated the effects of exposure to 9,10-PQ using mouse oocytes as a model system. We found that 9,10-PQ compromised meiotic maturation by impairing acentriolar microtubule organizing center (MTOC) assembly and subsequent spindle formation during meiotic maturation. Moreover, 9,10-PQ exposure prevented cell cycle progression by inhibiting Cdk1 activation via disturbance of cyclin B1 accumulation. Importantly, meiotic defects induced by 9,10-PQ exposure were not rescued by decreasing ROS levels, revealing that 9,10-PQ has ROS-independent activity that regulates cell cycle progression and spindle assembly. Therefore, our findings reveal that 9,10-PQ has novel activity that regulates cell-cycle progression and spindle formation in an ROS-independent manner during meiotic maturation in mouse oocytes.