Rutledge J C
Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, USA.
Mutat Res. 1997 Dec 12;396(1-2):113-27. doi: 10.1016/s0027-5107(97)00178-4.
Both a conceptual and a practical borderland between teratology and mutagenesis is early embryogenesis, the period between fertilization and gastrulation. Radiation and a variety of chemicals adversely affect the early conceptus leading to in utero mortality and malformations. The post-fertilization period of susceptibility differs from exposures of gametes, the later producing excessive pre- and peri-implantational death and low rates of fetal anomalies predominated by growth retardation. In contrast mutagen exposure of the zygote induces peri-implantational death, pan-gestational death and fetal anomalies predominated by hydrops, abdominal wall defects, and eye aberrations. The mechanism for this pathology remains unclear. These same agents produce a broader range of phenotypic anomalies during the remainder of pre-gastrulation development with anomalies overlapping those induced during organogenesis. Retinoic acid and 5-azacytidine administered prior to gastrulation produce novel malformation syndromes indicative of gene expression modification. The rates and types of defects from mutagen treatment of both gametes and the early conceptus contrast with those resulting from embryonic treatment during organogenesis, and the mechanisms are likely to differ. The pre-gastrulation period has not been explored to the extent reported during gametogenesis or organogenesis. Pre-gastrulation teratology is a new area of investigation with relevance both to reproductive toxicology and to mammalian developmental biology.
畸形学与诱变之间在概念和实践上的边缘领域是早期胚胎发生，即受精到原肠胚形成之间的时期。辐射和多种化学物质会对早期孕体产生不利影响，导致子宫内死亡和畸形。受精后的易感性时期与配子暴露不同，后者会导致植入前和植入期间过度死亡以及以生长迟缓为主的胎儿异常发生率较低。相比之下，合子的诱变剂暴露会导致植入期死亡、全孕期死亡以及以水肿、腹壁缺陷和眼部畸变为主的胎儿异常。这种病理的机制尚不清楚。在原肠胚形成前发育的其余阶段，这些相同的因素会产生更广泛的表型异常，这些异常与器官发生期间诱导的异常重叠。在原肠胚形成前给予视黄酸和5-氮杂胞苷会产生表明基因表达修饰的新型畸形综合征。对配子和早期孕体进行诱变处理所产生的缺陷发生率和类型与器官发生期间胚胎处理所产生的不同，其机制可能也不同。原肠胚形成前期尚未像配子发生或器官发生期间那样得到充分研究。原肠胚形成前畸形学是一个新的研究领域，与生殖毒理学和哺乳动物发育生物学都相关。
