Teratogenic effect of retinoic acid in swiss mice

Abstract

PURPOSE: To identify the types of malformations resulting from the administration of retinoic acid (RA) to Swiss mice on different days of pregnancy. METHODS: Twenty-four pregnant Swiss mice were divided into 4 groups of 6 animals each. The experimental groups received a single intraperitoneal injection of RA (70 mg/kg) on gestational days 7, 8 and 9 (D7, D8 and D9), while control animals (C) received only saline solution. RESULTS: Were obtained: exencephaly (C:0; D7:16.1%; D8:25.4%; D9:0), myelomeningocele (C:0; D7:25.8%, D8:30.9%, D9:0), spina bifida occulta (C:0, D7:29%, D8:41.8%, D90), gastroschisis (C:0, D7:6.4% D8:5.4%, D9:0), omphalocele (C:0, D7:6.4%, D8:14.5%, D9:0), lower limb alterations (C:0, D7:74.1%, D8:80%, D9:0), imperforated anus (C:0, D7:100%, D8:100%, D9:100%), and tail agenesis/alteration (C: D7:100%, D8:100%, D9:100%). CONCLUSION: The experimental model using Swiss mice proved to be efficient in the induction of the different types of defects, with the eighth gestational day being the one that most favored the induction of neural tube defect, omphalocele, gastroschisis, lower limb defects, imperforated anus and tail agenesis/alteration. On this basis, this is a useful model for future investigation of neural development and of the formation of the appendicular skeleton.

Identification of Stage-Specific Gene Expression Signatures in Response to Retinoic Acid during the Neural Differentiation of Mouse Embryonic Stem Cells

“…However, in vivo study indicated that high dose (70 mg/kg body weight; b.w.) of RA could induce teratogenic effects during gestational day 7–9 in Swiss mice (Veiga Quemelo et al, 2007). In addition, it was reported that the physiological dose that cannot affect RAR level was 1 mg/kg b.w.…”

A Role for All-Trans-Retinoic Acid in the Early Steps of Lymphatic Vasculature Development

“…Zebrafish that express mutant forms of the RA-metabolizing enzyme Cyp26A1 also display patterning defects in multiple organs, including the common cardinal vein, pectoral fin, tail, hindbrain and spinal cord. Because of the multitude of developmental defects caused by RA deficiency or exposure [54,55,56,57,58], we investigated the in vivo effects of RA exposure over only short time periods and during the earliest phases of lymphatic development.…”

Association of retinoic acid receptor genes with meningomyelocele

“…Low dosage administration of RA has been found to reduce the incidence of spinal NTDs in mouse models (Wilson et al, 2003; Maden, 2006). Conversely, RA when administered in teratogenic doses has been known to induce MM in several different rodent species (Danzer et al, 2005; Harris and Juriloff, 2007; Quemelo et al, 2007). These observations suggest that MM susceptibility could be associated with the genes in the RA signaling pathways.…”