Mitchard Terri, Kirk Sarah, Grant Claire, Stewart Jane
AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, United Kingdom.
AstraZeneca Pharmaceuticals, Macclesfield Campus, Macclesfield, Cheshire, United Kingdom.
Reprod Toxicol. 2017 Jan;67:140-145. doi: 10.1016/j.reprotox.2016.12.006. Epub 2016 Dec 30.
The effects on fetal weights and maternal health of taking 32μL blood microsamples at the end of organogenesis in a mouse embryofetal development (EFD) study design was investigated with the aim of reducing satellite animal usage. The effects of warming, handling and sampling either 3 or 6 times on gestation day 16 was evaluated. Maternal body weight gain was transiently reduced when animals underwent warming and handling with or without microsampling. Fetal weights on gestation day 18 were reduced after 6 occasion warming and handling alone or taking samples, but not when sampling was limited to 3 timepoints. Taking 3 microsamples of 32μL had no permanent adverse effects on maternal health or toxicologically significant effects on fetal development (measured by fetal weights). This regimen could be used to generate composite toxicokinetic profiles using only 6 main test animals in mouse EFD studies provided sampling procedures were matched across groups.
在一项小鼠胚胎胎儿发育（EFD）研究设计中，为了减少卫星动物的使用，研究了在器官发生期末采集32μL血液微量样本对胎儿体重和母体健康的影响。评估了在妊娠第16天进行3次或6次升温、处理和采样的影响。当动物接受升温、处理（无论是否进行微量采样）时，母体体重增加会暂时减少。单独进行6次升温、处理或采样后，妊娠第18天的胎儿体重会降低，但当采样限于3个时间点时则不会。采集3个32μL的微量样本对母体健康没有永久性不良影响，对胎儿发育（通过胎儿体重衡量）也没有毒理学上的显著影响。在小鼠EFD研究中，如果各实验组的采样程序一致，那么该方案仅使用6只主要实验动物即可用于生成复合毒代动力学图谱。
