Ochratoxin A exposure causes meiotic failure and oocyte deterioration in mice

Abstract

Ochratoxin A (OTA) is a mycotoxin produced by fungi and occurs naturally in various foodstuffs and some animal-derived products. This mycotoxin can cause deleterious effects on kidney, liver, central nervous, and immune system. However, potential mechanisms regarding how OTA disrupts the mammalian oocyte quality have not been clearly defined. In this study, we proved that OTA weakened oocyte quality by impairing oocyte meiotic maturation. We found that female mice treated with 1 mg/kg body weight OTA by intraperitoneal (IP) injection for 7 days displayed ovarian dysfunction and decreased offspring number. We also found that OTA treatment at 7.5 μM for 16 h decreased the rate of first polar body extrusion by disrupting spindle and chromosome alignment. In addition, OTA caused oxidative stress by inducing the accumulation of reactive oxygen species and consumption of antioxidants during meiosis, consequently resulting in oocytes apoptosis. Mitochondrial damage and insufficient energy supply were also observed in OTA-pretreated oocytes, which led to the meiotic failure of oocyte. Moreover, the epigenetic modifications were also affected, showing with altered 5 mC, 5hmC, H3K9ac, and H3K9me3 levels in mice oocytes. In summary, these results showed that OTA could decrease oocyte maturation and fertility by inducing oxidative stress and epigenetic changes.