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Involvement of CDKN1A (p21) in cellular senescence in response to heat and irradiation stress during preimplantation development.
Cell Stress and Chaperones ( IF 3.8 ) Pub Date : 2020-04-06 , DOI: 10.1007/s12192-020-01090-4
Sun-A Ock 1 , Jason G Knott 2, 3 , Inchul Choi 4
Affiliation  

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.

中文翻译:

植入前发育过程中,CDKN1A(p21)参与细胞衰老,以响应热量和辐射压力。

这项研究检查了细胞周期蛋白依赖性激酶抑制剂1a(CDK1A,p21)在小鼠植入前胚胎发育过程中对外源应激源的响应中的作用。将CDKN1A敲低(KD)单细胞合子暴露于39°C的热应激(HS)下4天或用1(1-Gy)或3(3-Gy)Gy X射线照射,及其发育能力和基因将表达与对照胚胎进行比较。CDKN1A KD和HS不影响早期卵裂或随后的胚胎发育。但是,HS延迟了空化并导致Cdkn1a升高在对照胚胎中的表达。暴露于1-Gy或3-Gy对发育到桑ula壳阶段没有影响。但是,许多桑ula无法发育到胚泡期。有趣的是,在1-Gy条件下,CDKN1A KD胚胎的胚泡发生率(77.7%)显着高于对照(44.4%)。总之,暴露于细胞应激因素会导致暴露于HS或X射线辐射的胚胎中Cdkn1a的上调,特别是对热应激或低剂量X射线辐射的响应,并且耗尽Cdkn1a mRNA可以减轻细胞周期停滞。这些发现表明,CDKN1A在植入前胚胎发育过程中的细胞衰老中起着至关重要的作用。
更新日期:2020-04-06
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