Folic Acid Deficiency during Late Gestation Decreases Progenitor Cell Proliferation and Increases Apoptosis in Fetal Mouse Brain

Abstract

In mice and rats, maternal dietary choline intake during late pregnancy modulates mitosis and apoptosis in progenitor cells of the fetal hippocampus and septum. Because choline and folate are interrelated metabolically, we investigated the effects of maternal dietary folate availability on progenitor cells in fetal mouse telencephalon. Timed-pregnant mice were fed a folate-supplemented (FS), control (FCT) or folate-deficient (FD) AIN-76 diet from d 11-17 of pregnancy. FD decreased the number of progenitor cells undergoing cell replication in the ventricular zones of the developing mouse brain septum (46.6% of FCT), caudate putamen (43.5%), and neocortex (54.4%) as assessed using phosphorylated histone H3 (a specific marker of mitotic phase) and confirmed by bromodeoxyuridine (BrdU) labeling of the S phase. In addition, 106.2% more apoptotic cells were found in FD than in FCT fetal septum. We observed 46.8% more calretinin-positive cells in the medial septal-diagonal band region of FD compared with pups from control dams. FS mice did not differ significantly from FCT mice in any of these measures. These results suggest that progenitor cells in fetal forebrain are sensitive to maternal dietary folate during late gestation.