Developmental exposures to three mammalian teratogens produces dysmorphic phenotypes in adult Caenorhabditis elegans.

Adult morphology was assessed at sublethal concentrations in C. elegans
using three mammalian teratogens, 5-fluorouracil (5FU), hydroxyurea (HU),
or ribavirin (RV). C. elegans develop from egg to adult with internal eggs
in about 70h at 20°C in C. elegans Habitation Medium (CeHM). Cohorts were
exposed from first feeding after hatching for either 24h (early-only) or
continuously for four days. Significant increases in the percentage of
prolapsed individuals were seen on the first day of adulthood in both
continuous and early-only 5FU and HU exposure groups. In contrast,
continuous RV exposures induced gonad arm and vulval anomalies that were
largely but not completely reversed in the early-only exposure groups.
Reductions in reproductive output with continuous exposures recovered,
though not fully, with early-only exposures for all three chemicals. To
our knowledge, this is the first systematic evaluation of C. elegans
morphology changes induced by mammalian teratogens. These data suggest
that C. elegans may be a useful model for detecting chemicals with human
teratogenic potential, but further studies using larger chemical test
panels are needed.

本研究以秀丽隐杆线虫（C. elegans）为模型，在亚致死浓度下采用三种哺乳动物致畸剂——5-氟尿嘧啶（5-fluorouracil，5FU）、羟基脲（hydroxyurea，HU）与利巴韦林（ribavirin，RV）对其成虫形态进行评估。秀丽隐杆线虫在20℃条件下于秀丽隐杆线虫培养基（C. elegans Habitation Medium，CeHM）中，约70小时即可完成从虫卵到携带体内卵的成虫的发育过程。实验队列从孵化后首次取食时开始暴露处理，分别设置仅暴露24小时（仅早期暴露组）与连续暴露4天两个处理组。在连续暴露组与仅早期暴露组的5FU、HU处理中，均可观察到成虫首日个体脱垂率显著升高。与之相反，连续暴露于RV的线虫会出现生殖腺臂与阴门畸形，而仅早期暴露组的该类畸形虽可得到大幅缓解，但无法完全逆转。对于三种受试化合物而言，连续暴露导致的繁殖力下降现象，在仅早期暴露处理中可得到部分恢复，但无法完全恢复。据我们所知，本研究是首次针对哺乳动物致畸剂诱导秀丽隐杆线虫形态变化开展的系统性评估。本研究数据表明，秀丽隐杆线虫可作为一种有效模型，用于筛查具有人类致畸潜力的化学物质，但后续仍需采用更大规模的化合物测试组开展进一步研究。