Effects of Ochratoxin A exposure on DNA damage in porcine granulosa cells in vitro

Toxicol Lett. 2020 May 23:330:167-175. doi: 10.1016/j.toxlet.2020.05.011. Online ahead of print.

Abstract

Ochratoxin A (OTA), a feed mycotoxin, tends to impair the reproductive performance of animals. Our previous studies have demonstrated that OTA exposure inhibits porcine ovarian granulosa cell (GC) proliferation and induces their apoptosis, but the underlying toxic mechanism is still uncertain. In this study, we explored the OTA exposure on porcine GCs in vitro and found that OTA exposure inhibited the proliferation of porcine GCs and arrested cell cycle of GCs in the G2/M phase. The results based on RNA-Seq revealed that 20 μM and 40 μM OTA exposure increase DNA damage of porcine GCs in vitro. The differentially expressed genes (DEGs) of 40 μM OTA exposure were enriched in the pathways of mismatch repair, nucleotide excision repair and homologous recombination in DNA replication compared with control group and 20 μM OTA exposure group. Meanwhile, OTA exposure increased the expression levels of DNA double-strand breaks (DSBs) gene γ-H2AX, and DNA repair related genes, such as BRCA1, XRCC1, PARP1, and RAD51. Above all, our research revealed that OTA might exert deleterious effects on porcine ovarian GCs, influencing DNA repair-related biological processes and causing DNA damage response.

Keywords: DNA damage; Ochratoxin A; Porcine granulosa cells; RNA-Seq.