GSE61213
Discovery of canonical and non-canonical miRNAs in brain frontal cortex in control and maternal nutrient restricted fetal baboon
We have developed a baboon nonhuman primate (NHP) model of maternal nutrient reduction during fetal development (30% global maternal nutrient reduction, MNR) to evaluate the impact of reduced nutrient availability on primate fetal development. We reported (Antonow-Schlorke et al. PNAS, 2011) that MNR induced major cerebral developmental disturbances at mid gestation (0.5G); however, the impact of MNR at late gestation (0.9G) and the mechanisms mediating these effects have not been determined. We hypothesized that MNR alters developmental trajectories of the fetal prefrontal cortex in the late gestation via miRNA regulation of key transcriptional and translational signaling pathways. Pregnant baboons were fed either ad libitum (control; CON; females n=3; males n=3) or a globally reduced diet (70% of controls; females n=3; males n=3) from 0.16G through 0.9G that produces IUGR (14% reduction in fetal weight). Fetuses were removed by Cesarean section at 0.9G, and prefrontal cortex (PFC) sections collected for analysis. Transcriptome (gene arrays) and small transcriptome (small RNA-Seq) analyses of fetal PFC were performed and gene and miRNA profiles were compared between MNR and CON. We present for the first time transcriptome (GSE42756) and small RNA transcriptome expression profiles of the fetal baboon PFC at 0.9G. Pathway analysis showed that MNR had sex-specific effects on key cellular signaling pathways. We conclude that moderate maternal global nutrient reduction during pregnancy can alter signaling pathways related to nutrient sensing and cell proliferation in the late gestation PFC. In addition, inverse expression of miRNAs known to target genes in these pathways suggests that miRNA mechanisms play a role in these changes. Overall design: Detection of miRNA profiles of 6 control and 6 maternal nutrient restricted (MNR) fetal frontal cortex