MORPHOLOGICAL MALFORMATIONS IN LIMBS AND SKELETAL STRUCTURES INDUCED BY RETINOIC ACID IN MOUSE EMBRYO (NMRI)

Abstract

Retinoic acid (RA) plays a key role in pattern formation along the major body axis and limbformation during vertebrate development. Exposure to excessive retinoic acid (in uterus) generatescongenital malformations in limbs, craniofacial, CNS, urogenital, heart, and axial skeletons. In thesestudies, seven groups of NMRI pregnant mice were administered a single gavage dose of 100 mg /kgbody weight; All-trans-retinoic acid dissolved in DMSO at days 9, 10, and 11 of gestation (groups 2, 4,6), DMSO at days 9, 10, and 11 (groups 1, 3, 5) and left (control group) untreated. Animals weresacrificed at day 18 of gestation via cesarean. Half of the total numbers (n=115) of fetuses wererandomly selected for histological studies, using hematoxylin-eosin methods, and others were used tostudy the skeletal defects. It was demonstrated that embryonic exposure to RA reveals that on day 9, 37% of forelimbs and 31% of hindlimbs have some abnormalities, and on days 10 and 11, 100% showdefects on craniofacial, vertebral column, ribs and limbs.