EFFECTS OF HEAT-SHOCK RESPONSE ON MAMMALIAN DEVELOPMENT

假设。一定比例的哺乳动物发育错误的基础 是不是基本基因座未能转录成信使核糖核酸并被翻译 在胚胎生命的关键时刻转化为蛋白质 细胞转录和翻译机制的先发制人 当时通过诱导所谓的热休克反应(HSR)。 实验性的。与胚胎应激假说有关的证据 通过研究热休克蛋白来寻找致畸机制(刚才所说的) 小鼠胚胎(HSP)的诱导：(I)小鼠组织在 制造高铁的各个发展阶段将被确定。(Ii) 无论是已知的还是可疑的致畸剂，都将接受检查 在器官发生期间到达胚胎并诱导HSR的能力(例如， 高温、乙醇和乙醛、沙利度胺、阿司匹林)。(Iii) 高铁蛋白血症胎儿发育缺陷的发生率和类型 是否在胚胎期被诱导将被确定。 意义重大。高铁在临界期的诱发 器官发生可能构成一种共同的途径，通过这种途径，不同的物理 和化学制剂会导致类似的畸形，品种和 缺陷的特异性取决于发育阶段 在诱导响应时已达到，并在 响应，而不是代理本身。

Hypothesis. The basis for a proportion of mammalian developmental errors is the failure of essential loci to be transcribed into mRNA and translated into protein at some critical moment during embryonic life as result of preemption of the transcriptional and translational machinery of the cell at that time by induction of the so-called heat-shock response (HSR). Experimental. Evidence pertaining to the embryonic stress hypothesis of teratogenesis (just stated) will be sought by studying heat-shock protein (HSP) induction in mouse embryos: (i) The ability of mouse tissues at various stages of development to make the HSR will be determined. (ii) Teratogenic agents, both known and suspected, will be examined for their ability to reach the embryo and induce the HSR during organogenesis (e.g., hyperthermia, ethanol and acetaldehyde, thalidomide, aspirin). (iii) The incidence and types of developmental defects in fetuses in which the HSR had been induced during the embryonic period will be determined. Significance. Induction of the HSR during the critical period of organogenesis could constitute a common pathway by which diverse physical and chemical agents would cause similar malformations, the variety and specificity of the defects depending on the developmental stage that had been reached when the response was induced, and on the duration of the response, rather than on the agent itself.