Sadler Thomas W
Senior Fellow, Greenwood Genetics Center, Greenwood, SC 29646, USA.
Department of Pediatrics, University of Utah, Salt Lake City, UT 84108, USA.
J Cardiovasc Dev Dis. 2017 Sep 11;4(3):15. doi: 10.3390/jcdd4030015.
A long standing axiom in the field of teratology states that the teratogenic period, when most birth defects are produced, occurs during the third to eighth weeks of development post-fertilization. Any insults prior to this time are thought to result in a slowing of embryonic growth from which the conceptus recovers or death of the embryo followed by spontaneous abortion. However, new insights into embryonic development during the first two weeks, including formation of the anterior-posterior, dorsal-ventral, and left-right axes, suggests that signaling pathways regulating these processes are prime targets for genetic and toxic insults. Establishment of the left-right (laterality) axis is particularly sensitive to disruption at very early stages of development and these perturbations result in a wide variety of congenital malformations, especially heart defects. Thus, the time for teratogenic insults resulting in birth defects should be reset to include the first two weeks of development.
致畸学领域一个长期存在的公理表明，产生大多数出生缺陷的致畸期发生在受精后发育的第三至第八周。在此之前的任何损伤被认为会导致胚胎生长减缓，胚胎能够从中恢复过来，或者导致胚胎死亡，随后自然流产。然而，对胚胎发育最初两周的新见解，包括前后轴、背腹轴和左右轴的形成，表明调节这些过程的信号通路是遗传和毒性损伤的主要靶点。左右（侧性）轴的建立在发育的非常早期阶段对干扰特别敏感，这些干扰会导致各种各样的先天性畸形，尤其是心脏缺陷。因此，导致出生缺陷的致畸损伤时间应重新设定，以包括发育的前两周。
