Department of Biological Sciences, Federal University of São Paulo, São Paulo, Brazil.
School of Bioprocess Engineering and Biotechnology, Federal University of Technology, Parana, Brazil.
Mol Reprod Dev. 2018 Nov;85(11):810-820. doi: 10.1002/mrd.23040. Epub 2018 Nov 8.
Exposure of the preimplantation embryo to heat stress triggers a series of cellular, molecular, and adaptive changes preventing a normal embryonic development. Heat stress disrupts the embryo cytoskeleton, intracellular calcium levels, mitochondrial function, and induces apoptosis. Moreover, heat stress can act indirectly through induction of reactive oxygen species (ROS), leading to a variety of cellular damage. Embryonic resistance to heat shock is determined by factors such as genotype, developmental stage, apoptosis, redox status, and regulatory molecules. The early embryo is very susceptible to heat stress; it acquires resistance to elevated temperature as development advances. One of the mechanisms involved in the developmental acquisition of thermotolerance is heat-induced apoptosis, which acts as a quality control mechanism to remove damaged blastomeres allowing the embryo to survive after stress. Although embryos at >8-cell stage can activate the apoptotic cascade as an adaptive response to stress, embryos at the two-cell stage are resistant to proapoptotic signals. This lack of apoptotic response has been associated to mitochondrial resistance to depolarization and epigenetic regulations, such as DNA methylation and histone deacetylation. Even though the cellular mechanisms triggered by heat stress have been studied, very little attention has been paid to the vulnerability of the epigenome to drastic temperature changes during the preimplantation period. Therefore, this review aims to characterize the effects of elevated temperature on the bovine embryo, especially addresissing developmental, cellular, and epigenetic alterations triggered in response to temperature.
胚胎暴露于热应激会引发一系列细胞、分子和适应性变化，从而阻止正常胚胎发育。热应激会破坏胚胎细胞骨架、细胞内钙离子水平、线粒体功能，并诱导细胞凋亡。此外，热应激还可以通过诱导活性氧（ROS）间接作用，导致多种细胞损伤。胚胎对热休克的抵抗力取决于遗传因素、发育阶段、凋亡、氧化还原状态和调节分子等因素。早期胚胎对热应激非常敏感；随着发育的进行，它会获得对高温的抗性。参与热耐受性发育获得的机制之一是热诱导的细胞凋亡，它作为一种质量控制机制，可去除受损的卵裂球，使胚胎在应激后存活。虽然 8 细胞期以上的胚胎可以激活凋亡级联作为对应激的适应性反应，但 2 细胞期的胚胎对促凋亡信号具有抗性。这种缺乏凋亡反应与线粒体对去极化的抗性和表观遗传调控有关，如 DNA 甲基化和组蛋白去乙酰化。尽管已经研究了热应激引发的细胞机制，但对于胚胎在植入前阶段经历剧烈温度变化时的表观基因组易损性却关注甚少。因此，本综述旨在描述高温对牛胚胎的影响，特别是探讨为应对温度变化而引发的发育、细胞和表观遗传改变。
