title: Investigation into the effect of microsampling on mouse fetuses and pregnant mice in the embryofetal development study design.
abstract: 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.
authors.affiliation: AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, United Kingdom.
authors.forename: Terri
authors.initials: T
authors.lastname: Mitchard
authors.affiliation: AstraZeneca Pharmaceuticals, Macclesfield Campus, Macclesfield, Cheshire, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kirk
authors.affiliation: AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, United Kingdom. Electronic address: claire.grant@astrazeneca.com.
authors.forename: Claire
authors.initials: C
authors.lastname: Grant
authors.affiliation: AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, United Kingdom.
authors.forename: Jane
authors.initials: J
authors.lastname: Stewart
mesh_terms: D023401:Animal Use Alternatives; D000818:Animals; D001800:Blood Specimen Collection / Q000009:adverse effects*; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D006234:Handling, Psychological; D006358:Hot Temperature; D051379:Mice; D011247:Pregnancy; D012107:Research Design; D018675:Toxicity Tests / Q000379:methods / Q000592:standards
keywords: 3Rs; Embryofetal development; Fetal weight; Fetus; Microsampling; Mouse