Neurodevelopmental Effects of Prenatal Bisphenol A Exposure on the Role of MicroRNA Regulating NMDA Receptor Subunits in the Rat Hippocampus

Maternal BPA exposure is known to cause learning and memory deficits in born offspring. However, little is known that the impairment is potentially caused by epigenetic modification. This study investigates the effect of prenatal BPA exposure on the microRNA expression: miR-19a and miR-539 encoding NMDA receptor subunits in the developing hippocampus with learning and memory functions when reaching adolescence. Pregnant Sprague Dawley rats were orally exposed at 5 mg/kg/day while the control was without BPA. The expression of miRNAs and NMDA receptor subunits in the hippocampus were examined at different stages of age by conducting the RT-PCR and Western Blot. The behavior of rats was then evaluated at adolescence age. Prenatal BPA exposure at 5 mg/kg/day was revealed to significantly reduce the expression of miR-19a and miR-539 concurrently with GRIN2A and GRIN2B expression at all stages of age. Consequently, the rats experience impairment in spatial and fear memory assessments compared to the control. Further, protein analysis revealed that GluN2A and GluN2B were also reduced before and after the assessment. The findings showed epigenetics modification on miR-19a and miR-539 during early development has been identified as one of the root causes of memory and learning impairment in rats when reaching adolescence.