Fipronil induces apoptosis and cell cycle arrest in porcine oocytes during in vitro maturation

Abstract

Fipronil (FPN) is a widely used phenylpyrazole pesticide that can kill pests by blocking γ-aminobutyric acid (GABA)-gated chloride channels. In addition, there are lack of studies on the effects of FPN on the female mammalian gametes. In this study, porcine oocytes were used to investigate the effects of FPN on the oocyte maturation process. The results showed that the first polar body extrusion rate significantly decreased (100 μM FPN vs. control, 18.64 ± 2.95% vs. 74.90 ± 1.50%, respectively), and oocytes were arrested at the germinal vesicle stage in 100 μM FPN group. Meanwhile, the FPN caused a significant increase in reactive oxygen species (ROS) levels and severe DNA damage inside the oocytes. Furthermore, apoptosis was enhanced along with decreases in mitochondrial membrane potential, BCL-xL, and the release of cytochrome C in FPN-treated group. Additionally, low CDK1 activity and delayed cyclin B1 degradation during germinal vesicle breakdown were found in the FPN-treated group, which resulted from the activation of ATM-P53-P21 pathway. In conclusion, FPN induces apoptosis and cell cycle arrest in porcine oocyte maturation because of increased ROS levels and DNA damage. This suggests that the FPN in the environment may have potential detrimental effects on the female mammalian reproductive system.

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Acknowledgement

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. 2018R1A2B6001173), Republic of Korea. Also, I would like to thank Doctor Namgoong for providing cyclin B1-GFP and H2B-mCherry expression plasmid.

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Correspondence to Jing Guo or Xiang-Shun Cui.

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Electronic supplementary material

Movie S1. Time-lapse imaging of control group during in vitro maturation.

Supplementary material 1 The oocytes were injected with H2B-mcherry (red) and cyclin B1-GFP (green) mRNAs and cultured in vitro for time-lapse imaging (AVI 15978 kb)

Movie S2. Time-lapse imaging of 100

Supplementary material 2  μM fipronil (FPN)-treated group during in vitro maturation. The oocytes were injected with H2B-mcherry (red) and cyclin B1-GFP (green) mRNAs and cultured in vitro for time-lapse imaging with 100 μM FPN treatment (AVI 13788 kb)

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Zhou, W., Niu, YJ., Nie, ZW. et al. Fipronil induces apoptosis and cell cycle arrest in porcine oocytes during in vitro maturation. Apoptosis 24, 718–729 (2019). https://doi.org/10.1007/s10495-019-01552-w

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Keywords

  • Fipronil
  • Porcine
  • Oocyte maturation
  • Apoptosis
  • MPF