Modulation of Retinoic Receptor Alpha and Beta and Its Links With Beta-catenin and Caspase-3 After Maternal Exposure to All-trans-retinoic Acid in KM Mouse Fetuses / 生物化学与生物物理进展

ABSTRACT

Epidemiologic studies suggest that intake of excess all-trans-retinoic acid (RA) during embryogenesis induces various developmental defects and the central nervous system (CNS) represents a major site of the teratogenic action of RA. It is therefore important to understand which parameters are affected early by excessive RA in order to devise and improve protective nutritional strategies. The modulations of beta-catenin and caspase-3 levels were investigated in the KM mouse embryo following maternal treatment with a single oral dose of 30mg/kg body weight of RA during the neurula period. In addition, retinoic receptors (RARs) are key transcription factors regulating gene expression in response to RA-activated signals. So the experiment was designed to evaluate whether the alterations in protein expression of RAR alpha and beta during the time of neural tube closure were induced by excessive RA. Maternal intake of excess RA induced early downregulation of RAR alpha and beta, beta-catenin and caspase-3 expression, which was followed by an increase in their expressive levels in the neural tube tissue of mouse embryos. This finding suggests that the alterations in the expression profile of RAR alpha and beta, beta-catenin and caspase-3 may be implicated in the teratogenesis induced by excess RA in KM mouse embryo.