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

Area of Science:

• Reproductive toxicology
• Developmental toxicology
• Animal welfare in research

Background:

• Reducing animal usage in toxicological studies is crucial.
• Embryofetal development (EFD) studies often require significant animal numbers.
• Microsampling techniques offer potential for reducing animal use.

Purpose of the Study:

• To investigate the effects of microsampling on maternal health and fetal development in mice.
• To evaluate the impact of sampling frequency (3 vs. 6 times) and associated procedures (warming, handling) on study outcomes.
• To determine if a 3-microsample regimen is viable for generating toxicokinetic profiles with reduced animal numbers.

Main Methods:

• Mouse embryofetal development (EFD) study design.
• Collection of 32μL blood microsamples on gestation day 16.
• Evaluation of maternal body weight gain and fetal weights on gestation day 18.
• Comparison of 3 sampling occasions versus 6 sampling occasions, with and without warming/handling.

Main Results:

• Transient reduction in maternal body weight gain observed with warming and handling, with or without sampling.
• Fetal weights were reduced on gestation day 18 following 6 sampling occasions (with/without handling), but not with 3 sampling occasions.
• No permanent adverse effects on maternal health or toxicologically significant effects on fetal development were found with the 3-microsample regimen.

Conclusions:

• A regimen of taking 3 microsamples of 32μL in mouse EFD studies does not cause permanent adverse effects.
• This microsampling approach can be used to generate composite toxicokinetic profiles with fewer animals (e.g., 6 main test animals).
• Standardized sampling procedures across groups are essential for the validity of this reduced-animal approach.