Rutledge J C, Generoso W M, Shourbaji A, Cain K T, Gans M, Oliva J
Department of Laboratory Medicine, Children's Hospital and Medical Center, Seattle, WA 98105.
Mutat Res. 1992 Dec;296(1-2):167-77. doi: 10.1016/0165-1110(92)90040-g.
Results of continuing studies indicate that the mouse zygote and two-cell embryo stages are a window of susceptibility in the experimental induction of congenital anomalies with certain mutagenic agents. The mechanisms by which the mutagens initiate the pathogenesis of these developmental defects are not known. However, in certain cases there is evidence that a nonconventional, perhaps epigenetic, mechanism is involved. Detailed characterization of the spectrum of anomalies induced and comparison of responses at the various stages exposed allowed classification of the mutagens generally into two groups. One group is characterized by being effective only in the early stages of zygote development and capable of producing a relatively high incidence of fetal death and hydrops. The other group affects all of the zygote stages studied as well as the two cell-embryo, but does not increase the incidence of fetal death and hydrops. Except for hydrops, chemicals in the two groups do not differ in terms of the types of anomalies present among malformed live fetuses, which bear a resemblance to a subset of common, sporadic human developmental anomalies that are of unknown etiology. This similarity raises the possibility that certain human developmental defects may have their origins in events that happen in the zygote and early pre-implantation stages.
持续研究结果表明，小鼠受精卵和二细胞胚胎阶段是某些诱变剂实验诱导先天性异常的易感性窗口。诱变剂引发这些发育缺陷发病机制尚不清楚。然而，在某些情况下，有证据表明涉及一种非常规的、可能是表观遗传的机制。对诱导的异常谱进行详细表征，并比较不同暴露阶段的反应，可将诱变剂大致分为两组。一组的特点是仅在受精卵发育早期有效，能够导致相对较高的胎儿死亡和水肿发生率。另一组影响所研究的所有受精卵阶段以及二细胞胚胎，但不会增加胎儿死亡和水肿的发生率。除水肿外，两组中的化学物质在畸形活胎儿中出现的异常类型方面没有差异，这些异常类似于病因不明的常见散发性人类发育异常的一个子集。这种相似性增加了某些人类发育缺陷可能起源于受精卵和植入前早期发生的事件的可能性。
