Investigation into the effect of microsampling on mouse fetuses and pregnant mice in the embryofetal development study design

- Pregnant mice warmed and handled with or without microsampling (32 mL per timepoint) on gestation day 16.
- Maternal animal had transiently reduced body weight gain compared with unhandled controls.
- Fetal weights reduced only when maternal blood samples were taken at 6 timepoints.
- No effect on fetal weights when maternal blood sampling limited to 3 occasions.
- This 3 timepoint 32 mL regimen could be used in mouse EFD studies when matched across groups

The effects on fetal weights and maternal health of taking 32 μL 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 32 μL 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.