Ochratoxin A Exposure Impairs Porcine Granulosa Cell Growth via the PI3K/AKT Signaling Pathway

J Agric Food Chem. 2019 Mar 6;67(9):2679-2690. doi: 10.1021/acs.jafc.8b06361. Epub 2019 Feb 25.

Abstract

The mycotoxin ochratoxin A (OTA), a naturally occurring food contaminant, has a toxic effect on the growth and development of follicles in pigs. However, little is known regarding the specific toxic effects of OTA exposure on oocytes and granulosa cells (GCs). In this study, we cultured porcine ovarian GCs and exposed them to OTA in vitro in order to explore the mechanism causing the negative effects. Initially, it was found that OTA exposure inhibited cell viability in a time and dose dependent manner. We also showed that OTA exposure increased oxidative stress, decreased proliferation ratio, and increased apoptosis ratio in GCs. We revealed an important role for the PI3K/AKT signal pathway in GC proliferation and apoptosis by RNA-seq analysis. The results not only showed that OTA treatment significantly affected the expression of genes within the PI3K/AKT pathway but also demonstrated a concrete relationship between the PI3K/AKT pathway and GC cell proliferation and apoptosis. In conclusion, the results demonstrated that OTA exposure impaired porcine GC growth via the PI3K/AKT signaling pathway.

Keywords: Granulosa cells; Ochratoxin A; PI3K/AKT signaling pathway; RNA-seq.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Female
  • Gene Expression / drug effects
  • Glutathione / analysis
  • Granulosa Cells / drug effects
  • Granulosa Cells / physiology*
  • Ochratoxins / toxicity*
  • Oxidative Stress / drug effects
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*
  • Swine*

Substances

  • Ochratoxins
  • ochratoxin A
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Glutathione