Exposure to citrinin induces DNA damage, autophagy, and mitochondria dysfunction during first cleavage of mouse...

Citrinin (CTN) is a mycotoxin, which is isolated from Penicillium citrinum and widely existed in the contaminated feeds. It is reported that CTN is toxic to heart, liver, and reproductive system. Previous studies indicated that CTN induced apoptosis in oocytes and embryos. In this study, we reported the potential causes of CTN on embryo development. Our results showed that 40 μM CTN exposure significantly reduced the first cleavage of mouse embryos, showing with the low rate of 2-cell embryos. We found that CTN induced DNA damage, showing the higher positive γH2A.X signals. Autophagy was occurred since more LC3 positive autophagosomes were found in the cytoplasm. This could be confirmed by the enhanced lysosome function, since higher accumulated lysosome distribution were found and LAMP2 was also increased under CTN exposure. Besides, we showed that mitochondria distribution was disturbed, indicating that CTN could disrupt mitochondria function, which could be the possible reason for the oxidative stress and apoptosis in CTN-exposed embryos. In conclusion, our study showed that CTN exposure had adverse effects on the early embryo development during first cleavage through its effects on the induction of DNA damage, autophagy, and mitochondria dysfunction.