Involvement of CDKN1A (p21) in cellular senescence in response to heat and irradiation stress during preimplantation development

Cell Stress Chaperones. 2020 May;25(3):503-508. doi: 10.1007/s12192-020-01090-4. Epub 2020 Apr 6.

Abstract

This study examined the role of cyclin-dependent kinase inhibitor 1a (CDK1A, p21) in response to exogenous stressors during mouse preimplantation embryo development. CDKN1A knockdown (KD) one-cell zygotes were exposed to 39 °C heat stress (HS) for 4 days or irradiated by 1 (1-Gy) or 3 (3-Gy) Gy X-rays, and their developmental competence and gene expression were compared with control embryos. CDKN1A KD and HS did not influence early cleavage or subsequent embryonic development; however, HS delayed cavitation and induced elevated Cdkn1a expression in control embryos. Exposure to 1- or 3-Gy had no effect on development to the morula stage; however, a significant number of morulae failed to develop to the blastocyst stage. Interestingly, under the 1-Gy condition, the blastocyst rate of CDKN1A KD embryos (77.7%) was significantly higher than that of the controls (44.4%). In summary, exposure to cellular stressors resulted in the upregulation of Cdkn1a in embryos exposed to HS or X-ray irradiation, particularly in response to heat stress or low-dose X-ray irradiation, and depleting Cdkn1a mRNA alleviated cell cycle arrest. These findings suggest that CDKN1A plays a vital role in cellular senescence during preimplantation embryo development.

Keywords: Cdkn1a; Heat stress; Irradiation; Preimplantation; Senescence; p21.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / metabolism
  • Blastocyst / radiation effects
  • Cellular Senescence*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21 / physiology
  • DNA Damage
  • Embryonic Development* / radiation effects
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Hot Temperature
  • Mice
  • RNA, Messenger / metabolism
  • Stress, Physiological* / genetics
  • X-Rays

Substances

  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • RNA, Messenger