ALTERED EXPRESSION OF PULMONARY SURFACTANT PROTEIN-A VIA IN-UTERO EXPOSURE TO HIGH CONCENTRATIONS OF FOLIC ACID

Purpose: Folic acid, a member of the family of B vitamins, is provided in elevated concentrations to pregnant women to prevent congenital birth deformities such as cleft palate and neural tube defects. Previous studies have shown in-utero exposure to high concentrations of folic acid can negatively regulate gene expression via hypermethylation of DNA and/or histones in promoter regions of developmentally regulated genes. Our study aims to show a similar effect on the lung-specific, developmentally regulated gene, surfactant protein-A (SP-A) in the fetal lungs of ICR mice exposed in-utero to high concentrations of dietary folic acid. Appropriate SP-A expression is necessary for the normal development and regulation of multiple aspects of the innate and acquired arms of the immune system. Methods: Outbred ICR mice (n=8) were placed on a diet supplemented with high levels of folic acid (HMD) along with the necessary cofactors for methyl metabolism. A control group (n=8) was placed on a standard diet. Multiple rounds of breeding were conducted until four distinct timepoints were collected. The fetal-lung tissues were harvested at the last four days of gestation: 15, 16, 17, and 18 days post-coitum (dpc), respectively. A significant suppression of SP-A, SP-B, and SP-D at term was revealed in the HMD group when quantitative real-time PCR (qRT-PCR) data were analyzed via the comparative CT method. Results: Increased expression of cyclooxygenase 1 and 2 (COX-1, COX-2), markers of inflammation, was observed in these same mice at 17 dpc. Conclusions: These findings suggest a possible predisposition for pulmonary dysfunction in HMD mice as a result of decreased expression of the anti-inflammatory, SP-A.