PMID- 32253738 OWN - NLM STAT- MEDLINE DCOM- 20210524 LR - 20240209 IS - 1466-1268 (Electronic) IS - 1355-8145 (Print) IS - 1355-8145 (Linking) VI - 25 IP - 3 DP - 2020 May TI - Involvement of CDKN1A (p21) in cellular senescence in response to heat and irradiation stress during preimplantation development. PG - 503-508 LID - 10.1007/s12192-020-01090-4 [doi] AB - 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 degrees 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. FAU - Ock, Sun-A AU - Ock SA AD - Rural Development Administration, National Institute of Animal Science, 1500 Kongjwipatjwi-ro, Isero-myeon, Wanju-gun, Jeollabuk-do, 55365, Republic of Korea. FAU - Knott, Jason G AU - Knott JG AD - Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University, East Lansing, MI, USA. knottj@msu.edu. AD - Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, East Lansing, MI, USA. knottj@msu.edu. FAU - Choi, Inchul AU - Choi I AUID- ORCID: 0000-0001-5011-2658 AD - Division of Animal and Dairy Sciences, College of Agriculture and Life Sciences, Chungnam National University, Daejeon, 34134, Republic of Korea. icchoi@cnu.ac.kr. LA - eng GR - R01 HD095371/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200406 PL - Netherlands TA - Cell Stress Chaperones JT - Cell stress & chaperones JID - 9610925 RN - 0 (Cdkn1a protein, mouse) RN - 0 (Cyclin-Dependent Kinase Inhibitor p21) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Blastocyst/metabolism/radiation effects MH - *Cellular Senescence MH - Cyclin-Dependent Kinase Inhibitor p21/genetics/*metabolism/physiology MH - DNA Damage MH - *Embryonic Development/radiation effects MH - Gene Expression Regulation, Developmental MH - Gene Knockdown Techniques MH - Hot Temperature MH - Mice MH - RNA, Messenger/metabolism MH - *Stress, Physiological/genetics MH - X-Rays PMC - PMC7193008 OTO - NOTNLM OT - Cdkn1a OT - Heat stress OT - Irradiation OT - Preimplantation OT - Senescence OT - p21 COIS- The authors declare that they have no conflicts of interest. EDAT- 2020/04/08 06:00 MHDA- 2021/05/25 06:00 PMCR- 2020/11/01 CRDT- 2020/04/08 06:00 PHST- 2019/10/01 00:00 [received] PHST- 2020/03/10 00:00 [accepted] PHST- 2020/02/15 00:00 [revised] PHST- 2020/04/08 06:00 [pubmed] PHST- 2021/05/25 06:00 [medline] PHST- 2020/04/08 06:00 [entrez] PHST- 2020/11/01 00:00 [pmc-release] AID - S1355-8145(23)01220-8 [pii] AID - 1090 [pii] AID - 10.1007/s12192-020-01090-4 [doi] PST - ppublish SO - Cell Stress Chaperones. 2020 May;25(3):503-508. doi: 10.1007/s12192-020-01090-4. Epub 2020 Apr 6.