Gene expression in teratogenic exposures: a new approach to understanding individual risk

The phenomenon of partial or incomplete penetrance is common to many paradigms of exposure to teratogens, where only some of the exposed individuals exhibit developmental defects. We here argue that the most widely used experimental approaches in reproductive toxicology do not take partial penetrance into account, and are thus likely to miss differences between affected and unaffected individuals that contribute to susceptibility for teratogenesis. We propose that focus on the variation between exposed individuals could help to discover factors that may play a causative role for abnormal developmental processes that occur with incomplete penetrance. Total RNA was extracted from individual embryos E10.5 derived from normal and diabetic pregnancies. A total of 8 sample pools were created, 4 resultiing from normal (C1-C4) and 4 from diabetic (E1-E4) pregnancies. Each pool consisted of RNA from 4 embryos obtained from 4 different pregnancies. Samples E5-E8 consisted of individual embryos with NT defects obtained from diabetic pregnancies.

部分或不完全外显率（partial penetrance）现象广泛存在于致畸原（teratogens）暴露的诸多实验范式中，仅部分暴露个体会表现出发育缺陷。我们在此指出，当前生殖毒理学（reproductive toxicology）领域应用最广泛的实验方法未将不完全外显率纳入考量范畴，因此极有可能遗漏受影响个体与未受影响个体间的差异——这类差异恰恰是致畸易感性的重要贡献因素。本研究提出，聚焦暴露个体间的异质性，或可助力发掘在不完全外显模式下引发异常发育过程的致病相关因子。本研究从正常妊娠与糖尿病妊娠来源的E10.5期胚胎（embryos E10.5）中提取总RNA（total RNA）。共构建8个样本混合池：其中4个来自正常妊娠组（标记为C1-C4），另外4个来自糖尿病妊娠组（标记为E1-E4）。每个混合池均包含4份来自不同妊娠的胚胎的总RNA。此外，样本E5-E8则取自糖尿病妊娠来源的、携带神经管缺陷（NT defects）的单个胚胎。