Zearalenone exposure triggered porcine granulosa cells apoptosis via microRNAs-mediated focal adhesion pathway.

Abstract Zearalenone (ZEA), a metabolite of Fusarium, which is commonly found in moldy feed crops, is a well-known exogenous endocrine disruptor and has serious negative effects on animal reproduction. In order to understand the toxic effects of ZEA exposure on porcine granulosa cells (pGCs), which were exposed to 10 μM and 30 μM ZEA for 48 h in vitro, several methods were used for analysis. Flow cytometry and TUNEL analysis showed that the apoptosis of pGCs significantly increased in a dose-dependent manner after ZEA exposure compared with that of the control group. Whole transcriptome RNA-seq analysis was performed to reveal the mRNAs and miRNAs expression changes of pGCs after ZEA exposure and it was found that the expression of apoptosis-related genes was altered after ZEA exposure, and miRNAs were also significantly different among the experimental groups. In particular, ZEA exposure affected the expression of miRNAs associated with apoptosis-related pathways, such as miR-744, miR-1343 and miR-331-3p, as well as focal adhesion pathways related genes, Pak4 and Elk1, which were also involved in the apoptosis-related pathways. Moreover, the regulation networks between apoptosis-related mRNA and miRNAs were confirmed with the results of RT-qPCR and immunofluorescence. In conclusion, our results here demonstrated that ZEA exposure impaired pGCs growth and apoptosis via miRNAs-mediated focal adhesion pathway.