Relief of endoplasmic reticulum stress enhances DNA damage repair and improves development of pre-implantation embryos

PLoS One. 2017 Nov 3;12(11):e0187717. doi: 10.1371/journal.pone.0187717. eCollection 2017.

Abstract

Early-cleaving embryos are known to have better capacity to reach the blastocyst stage and produce better quality embryos compared to late-cleaving embryos. To investigate the significance of endoplasmic reticulum (ER) stress on early embryo cleavage kinetics and development, porcine embryos produced in vitro were separated into early- and late-cleaving groups and then cultured in the absence or presence of the ER stress inhibitor tauroursodeoxycholic acid (TUDCA). Developing embryos were collected at days 3 to 7 of culture for assessment of ER stress status, incidence of DNA double-strand breaks (DSBs), development and total cell number. In the absence of TUDCA treatment, late-cleaving embryos exhibited ER stress, higher incidence of DNA DSBs, as well as reductions in development to the blastocyst stage and total embryo cell numbers. Treatment of late-cleaving embryos with TUDCA mitigated these effects and markedly improved embryo quality and development. These results demonstrate the importance of stress coping responses in early developing embryos, and that reduction of ER stress is a potential means to improve embryo quality and developmental competence.

MeSH terms

  • Animals
  • Blastocyst*
  • DNA Damage*
  • DNA Repair*
  • Embryonic Development / genetics*
  • Endoplasmic Reticulum Stress / drug effects*
  • Female
  • Real-Time Polymerase Chain Reaction
  • Swine
  • Taurochenodeoxycholic Acid / pharmacology*

Substances

  • Taurochenodeoxycholic Acid
  • ursodoxicoltaurine

Grants and funding

This study is supported by grants (262085-2011 to V.B. and 2015-04390 to L.B.A.) from the Natural Sciences and Engineering Research Council of Canada (NSERC). K.G. and R.C.B. are recipients of Science Without Borders Program Scholarships from the Brazilian Council of Scientific and Technological Development. N.D. is a recipient of an Alexander Graham Bell Canada Graduate Scholarship from the Natural Sciences and Engineering Research Council of Canada. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.