Zheng Ping, Schramm R Dee, Latham Keith E
The Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Biol Reprod. 2005 Jun;72(6):1359-69. doi: 10.1095/biolreprod.104.039073. Epub 2005 Feb 9.
DNA repair is essential for maintaining genomic integrity, and may be required in the early embryo to correct damage inherited via the gametes, damage that arises during DNA replication, or damage that arises in response to exposure to genotoxic agents. The capacity of preimplantation stage mammalian embryos to repair damaged DNA has not been well characterized, particularly in primate embryos. In this study, we examined the expression of 48 mRNAs related to sensing different kinds of DNA damage, repairing that DNA damage, and controlling the cell cycle to provide an opportunity for DNA repair. The expression data reveal dynamic temporal changes, indicating a changing ability of the rhesus embryo to detect and repair different kinds of DNA damage. Low expression or overexpression of specific DNA repair genes may limit the ability of the embryo to respond to DNA damage at certain stages. Additionally, our data reveal that in vitro culture may lead to dysregulation of many such genes and a potentially impaired ability to repair DNA damage, thus affecting cellular viability and long-term embryo viability via effects on genome integrity. This effect of in vitro culture on nonhuman primate embryos may be relevant to assessing the potential advantages and disadvantages of prolonged in vitro culture of human embryos.
DNA修复对于维持基因组完整性至关重要,在早期胚胎中可能需要修复通过配子遗传的损伤、DNA复制过程中出现的损伤或因暴露于基因毒性剂而产生的损伤。着床前阶段哺乳动物胚胎修复受损DNA的能力尚未得到充分表征,尤其是在灵长类胚胎中。在本研究中,我们检测了48种与感知不同类型DNA损伤、修复该DNA损伤以及控制细胞周期以提供DNA修复机会相关的mRNA的表达。表达数据揭示了动态的时间变化,表明恒河猴胚胎检测和修复不同类型DNA损伤的能力在不断变化。特定DNA修复基因低表达或过表达可能会限制胚胎在某些阶段对DNA损伤作出反应的能力。此外,我们的数据表明,体外培养可能导致许多此类基因失调,并可能损害修复DNA损伤的能力,从而通过影响基因组完整性影响细胞活力和胚胎长期存活能力。体外培养对非人灵长类胚胎的这种影响可能与评估人类胚胎延长体外培养的潜在优缺点有关。