Pretreatment Effect of Folic Acid on 13-Cis-RA-Induced Cellular Damage of Developing Midfacial Processes in Cultured Rat Embryos

The Open Dentistry Journal 31 Mar 2017 RESEARCH ARTICLE DOI: 10.2174/1874210601711010200



Excess treatment of 13-cis-RA (Accutane®) on pregnant women induces craniofacial malformation found in infants. However, the effect of folic acid on 13-cis-RA-induced cellular damages of developing midfacial processes is still unknown. The purpose of this study was to investigate the pretreatment effect of folic acid (FA) on 13-cis-RA-induced cellular damage in developing midfacial processes in rat embryos.

Materials and Methods:

The rat embryos at developing midfacial processes were performed by whole embryo culture in vitro, in the presence of 13-cis-RA (20 µM) with or without pre-treatment of FA (100 µM). The midfacial morphogenesis score, PCNA and TUNEL assay staining were evaluated for morphogenesis, cell proliferation and apoptosis of the midfacial processes, respectively.


The 13-cis-RA-treated embryos at 24h showed atrophy of midfacial processes with significantly decreased morphogenesis score and cell proliferation, and increased apoptotic cell death. In contrast, the embryos pre-treated with FA for 18h, followed by 13-cis-RA treatment for 24h (FA-RA) showed significantly greater morphogenesis score, increased cell proliferation and lower apoptotic cell death compared to those of the 13-cis-RA-treated embryos.


The results suggest that FA reduced the teratogenic effects of 13-cis-RA on midfacial process tissue. Future investigations regarding the anti-teratogenic mechanism of FA on the prevention of damages in midface processes induced by 13-cis-RA on pregnant woman are warranted.

Keywords: Apoptosis, Cell proliferation, Folic acid, Midfacial process, 13-Cis-RA, Rat embryo.
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