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Effects of Ochratoxin A exposure on DNA damage in porcine granulosa cells in vitro
Toxicology Letters ( IF 2.9 ) Pub Date : 2020-09-01 , DOI: 10.1016/j.toxlet.2020.05.011
Tian-Yu Zhang 1 , Li Kong 2 , Jia-Xing Hao 3 , Han Wang 2 , Zi-Hui Yan 2 , Xiao-Feng Sun 2 , Wei Shen 2
Affiliation  

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.

中文翻译:


赭曲霉毒素A暴露对体外猪颗粒细胞DNA损伤的影响



赭曲霉毒素 A (OTA) 是一种饲料霉菌毒素,往往会损害动物的繁殖性能。我们前期的研究表明,OTA暴露可抑制猪卵巢颗粒细胞(GC)增殖并诱导其凋亡,但潜在的毒性机制仍不确定。在本研究中,我们在体外探索了OTA暴露对猪GCs的影响,发现OTA暴露抑制了猪GCs的增殖,并使GCs的细胞周期停滞在G2/M期。基于 RNA-Seq 的结果表明,20 μM 和 40 μM OTA 暴露会增加体外猪 GC 的 DNA 损伤。与对照组和20 μM OTA暴露组相比,40 μM OTA暴露的差异表达基因(DEG)在DNA复制中的错配修复、核苷酸切除修复和同源重组途径中富集。同时,OTA暴露增加了DNA双链断裂(DSB)基因γ-H2AX和DNA修复相关基因(例如BRCA1、XRCC1、PARP1和RAD51)的表达水平。最重要的是,我们的研究表明,OTA 可能对猪卵巢 GC 产生有害影响,影响 DNA 修复相关的生物过程并引起 DNA 损伤反应。
更新日期:2020-09-01
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