Effects of Trichostatin A and PXD101 on the In Vitro Development of Mouse Somatic Cell Nuclear Transfer Embryos

Xiaoyan Qiu1, Haihong You1, Xiong Xiao1

  • 1Embryo Engineering Laboratory, School of Animal Science and Technology, Southwest University , Chong Qing, P.R. China .

Cellular Reprogramming
|January 24, 2017
PubMed

Insights

Histone deacetylase inhibitors (HDACis) improve animal cloning. This study found that trichostatin A (TSA) and PXD101 significantly enhance mouse somatic cell nuclear transfer (SCNT) embryo development and stem cell establishment.

Area of Science:

  • Reproductive biology
  • Developmental biology
  • Epigenetics

Background:

  • Somatic cell nuclear transfer (SCNT) cloning has low success rates due to epigenetic reprogramming issues.
  • Histone deacetylase inhibitors (HDACis) are known to improve SCNT embryo development.
  • Trichostatin A (TSA) is a known HDACi that enhances SCNT embryo development in various species.

Purpose of the Study:

  • To compare the efficacy of two different SCNT protocols using TSA.
  • To investigate the effect of a new HDACi, PXD101 (belinostat), on mouse SCNT embryo development for the first time.
  • To optimize TSA concentration and treatment timing for SCNT.

Main Methods:

  • Mouse SCNT embryos were treated with either TSA (5 nM) or PXD101 (50 nM) during and after activation.
  • Developmental rates to blastocyst stage were assessed.
  • The ability to establish nuclear transfer-derived embryonic stem cells (NT-ESCs) was evaluated.

Main Results:

  • TSA treatment resulted in a 39.1% blastocyst development rate, while PXD101 treatment yielded 40.2%.
  • Both TSA and PXD101 treatments significantly increased blastocyst rates compared to non-treated SCNT embryos (11.5%).
  • NT-ESC establishment rates were significantly higher in both treatment groups (38.1% for TSA, 40.9% for PXD101) compared to the control group (11.8%).

Conclusions:

  • Optimized TSA concentration and treatment timing enhance mouse SCNT embryo development.
  • PXD101 significantly improves in vitro development of mouse SCNT embryos and NT-ESC establishment.
  • HDACis represent a promising strategy for improving SCNT efficiency and reprogramming in mammals.