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

Ock, Sun-A; Knott, Jason G.; Choi, Inchul

doi:10.1007/s12192-020-01090-4

Original Paper
Published: 06 April 2020

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

Cell Stress and Chaperones volume 25, pages 503–508 (2020)Cite this article

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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.

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Funding

The work was supported by Chungnam National University (2019-0635-01 to IC), Republic of Korea, and by R01HD095371 from the National Institute of Child Health and Development to J.G.K.

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Affiliations

Rural Development Administration, National Institute of Animal Science, 1500 Kongjwipatjwi-ro, Isero-myeon, Wanju-gun, Jeollabuk-do, 55365, Republic of Korea
Sun-A Ock
Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University, East Lansing, MI, USA
Jason G. Knott
Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, East Lansing, MI, USA
Jason G. Knott
Division of Animal and Dairy Sciences, College of Agriculture and Life Sciences, Chungnam National University, Daejeon, 34134, Republic of Korea
Inchul Choi

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Sun-A Ock
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Jason G. Knott
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Inchul Choi
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Correspondence to Jason G. Knott or Inchul Choi.

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Ock, SA., Knott, J.G. & Choi, I. Involvement of CDKN1A (p21) in cellular senescence in response to heat and irradiation stress during preimplantation development. Cell Stress and Chaperones 25, 503–508 (2020). https://doi.org/10.1007/s12192-020-01090-4

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Received: 01 October 2019
Revised: 15 February 2020
Accepted: 10 March 2020
Published: 06 April 2020
Issue Date: May 2020
DOI: https://doi.org/10.1007/s12192-020-01090-4

Keywords

Cdkn1a
p21
Heat stress
Senescence
Irradiation
Preimplantation