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PsA inhibits the development of bovine embryos through epigenetic and oxidative stress

Xin Ma1, Chenglin Zhan1, Panpan Ma1,2

  • 1College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin, China.

American Journal of Veterinary Research
|February 16, 2023
PubMed
Abstract

Insights

Psammaplin A (PsA) inhibits bovine embryo development by decreasing pluripotency gene expression and increasing oxidative stress. This suggests careful clinical application of PsA to avoid reproductive toxicity.

Area of Science:

  • Reproductive biology and developmental toxicology.
  • Epigenetics and its role in early development.
  • Histone deacetylase inhibitors (HDACi) and their effects on cellular processes.

Background:

  • Histone deacetylases (HDACs) regulate crucial processes like embryo development and tumor progression.
  • HDACs are frequently dysregulated in tumor cells and somatic cell nuclear transfer (SCNT) embryos.
  • Psammaplin A (PsA) is a potent HDAC inhibitor with potential therapeutic applications.

Purpose of the Study:

  • To investigate the impact of PsA on the preimplantation development of bovine parthenogenetic (PA) embryos.
  • To analyze the effects of PsA on key developmental genes and epigenetic modifications in bovine embryos.
  • To evaluate the potential reproductive toxicity of PsA.

Main Methods:

  • Treatment of approximately 2,400 bovine PA embryos with varying concentrations and durations of PsA.
  • Analysis of blastocyst formation rates.
  • Assessment of pluripotency gene (Nanog) expression.
  • Measurement of histone acetylation (H3K9), DNA methylation, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), and superoxide dismutase 1 (SOD1) activity.

Main Results:

  • PsA significantly reduced blastocyst formation rates in a dose- and time-dependent manner.
  • PsA decreased Nanog expression and inhibited HDAC1 and DNMT1.
  • PsA enhanced H3K9 acetylation, increased ROS generation, and decreased MMP and SOD1 activity, indicating oxidative stress.

Conclusions:

  • PsA inhibits bovine preimplantation PA embryo development, highlighting the need for caution in clinical applications to prevent reproductive toxicity.
  • The reproductive toxicity of PsA may be linked to increased oxidative stress in embryos.
  • Combining PsA with antioxidants like melatonin could be a viable strategy for clinical use, mitigating adverse effects.

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