Dose-response for retinoic acid-induced forelimb malformations and cleft palate: a comparison of computerized image analysis and visual inspection

Birth Defects Research. Part B, Developmental and Reproductive Toxicology
Jerry L CampbellD Alan Warren

Abstract

The objectives of this study were to (1) compare two techniques (computerized image analysis and visual morphological evaluation) for the assessment of fetal forelimb malformations and (2) increase the robustness of the dose-response curve for forelimb and cleft palate malformations resulting from all-trans retinoic acid (RA) exposure in GD 11 mice. Pregnant CD-1 mice were administered a single oral dose of all-trans RA (0, 2.5, 10, 30, 60, or 100 mg/kg) on GD 11. GD 18 fetuses were examined for malformations using visual morphological scoring and computerized image analysis. Dose-dependent changes occurred in the size and shape of the humerus, radius, and ulna based on both assessment methodologies. The most sensitive indicators for the lowest effect level (10 mg/kg) on forelimbs were roundness, a shape measurement determined by image analysis, and visual morphological scoring. For all other bone measurements (proximal and distal width, area, length, and perimeter), the lowest effect level was 30 mg/kg. The maximum effect for limb defects and total malformed fetuses was seen at 60 mg/kg and higher. Incidence of cleft palate increased over the entire range of administered doses reaching a maximum of 74% (100 mg/kg). Overall, re...Continue Reading

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Citations

Sep 13, 2007·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·John MakrakisM Jane Black
May 27, 2010·The Cleft Palate-craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association·Mu ChenDa-Wei Wang
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Dec 22, 2006·Birth Defects Research. Part A, Clinical and Molecular Teratology·Jing HanYong Li
Oct 27, 2006·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Jing HanYong Li
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Nov 18, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Zengli YuYong Li
Aug 30, 2017·Molecular Medicine Reports·Shiyi DongHongzhang Huang

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Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.