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 limb formation during vertebrate development. Exposure to excessive retinoic acid (in uterus) generates congenital malformations in limbs, craniofacial, CNS, urogenital, heart, and axial skeletons. In these studies, seven groups of NMRI pregnant mice were administered a single gavage dose of 100 mg /kg body 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 were sacrificed at day 18 of gestation via cesarean. Half of the total numbers (n=115) of fetuses were randomly selected for histological studies, using hematoxylin-eosin methods, and others were used to study 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 % show defects on craniofacial, vertebral column, ribs and limbs