TY - JOUR
T1 - Refinement of a morphological scoring system for postimplantation rabbit conceptuses
AU - Carney, Edward W.
AU - Tornesi, Belen
AU - Keller, Charles
AU - Findlay, Heather A.
AU - Nowland, William S.
AU - Marshall, Valerie A.
AU - Ozolinš, Terence R.S.
PY - 2007/6
Y1 - 2007/6
N2 - BACKGROUND: The rabbit is used extensively in developmental toxicity testing, yet basic information on rabbit embryo development is lacking. The goals of this study were to refine a rabbit embryo morphology scoring system, and use it to evaluate rabbit whole embryo cultures (WEC). METHODS: A total of 265 conceptuses were harvested between GD 8.0 and 12.0 (coitus = GD 0) at 6-hr intervals and examined in detail. Discreet developmental landmarks were then established for 18 morphological features and assigned scores ranging from 0 up to 6. The scoring system was then validated on a subset of randomly selected in vivo conceptuses, and was used to evaluate conceptuses grown for 12, 24, 36, or 48 hr in WEC beginning from GD 9.0 or 10.0. A few embryos also were examined using microscopic computed tomography (microCT)-based virtual histology™ to assess the utility of this technology. RESULTS: Morphology scores of in vivo developed conceptuses increased linearly (r2 = 0.98) with advancing gestational age, from means of 0.0 on GD 8.0 to 67.9 on GD 12.0. Application of the scoring system, supplemented with evidence from Virtual histology™, indicated that the WEC system supported normal morphological development of rabbit conceptuses. However, when explanted at GD 9, the rate of development was about 20% slower than in vivo, whereas the rate of development in WEC from GD 10 was indistinguishable from in vivo. CONCLUSIONS: This work enhances the evaluation tools available to study mechanisms of normal and abnormal development in this widely used animal testing species.
AB - BACKGROUND: The rabbit is used extensively in developmental toxicity testing, yet basic information on rabbit embryo development is lacking. The goals of this study were to refine a rabbit embryo morphology scoring system, and use it to evaluate rabbit whole embryo cultures (WEC). METHODS: A total of 265 conceptuses were harvested between GD 8.0 and 12.0 (coitus = GD 0) at 6-hr intervals and examined in detail. Discreet developmental landmarks were then established for 18 morphological features and assigned scores ranging from 0 up to 6. The scoring system was then validated on a subset of randomly selected in vivo conceptuses, and was used to evaluate conceptuses grown for 12, 24, 36, or 48 hr in WEC beginning from GD 9.0 or 10.0. A few embryos also were examined using microscopic computed tomography (microCT)-based virtual histology™ to assess the utility of this technology. RESULTS: Morphology scores of in vivo developed conceptuses increased linearly (r2 = 0.98) with advancing gestational age, from means of 0.0 on GD 8.0 to 67.9 on GD 12.0. Application of the scoring system, supplemented with evidence from Virtual histology™, indicated that the WEC system supported normal morphological development of rabbit conceptuses. However, when explanted at GD 9, the rate of development was about 20% slower than in vivo, whereas the rate of development in WEC from GD 10 was indistinguishable from in vivo. CONCLUSIONS: This work enhances the evaluation tools available to study mechanisms of normal and abnormal development in this widely used animal testing species.
KW - Comparative development
KW - Embryo
KW - Morphology
KW - Whole embryo culture
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U2 - 10.1002/bdrb.20118
DO - 10.1002/bdrb.20118
M3 - Article
C2 - 17570508
AN - SCOPUS:34447252338
SN - 1542-9733
VL - 80
SP - 213
EP - 222
JO - Birth Defects Research Part B - Developmental and Reproductive Toxicology
JF - Birth Defects Research Part B - Developmental and Reproductive Toxicology
IS - 3
ER -