Figure 4

Characterisation of secreted miRNAs and transcriptome changes in the fetal brain. (a–f) Predicted targets of miRNAs that were significantly altered in response to maternal hypoxia in conditioned medium from rat placenta (a–c) or in fetal plasma (d–f) were analysed for enrichment of tissue types (a,d) and of biological processes (b,e). Predicted targets of all miRNAs, of upregulated miRNAs and of downregulated miRNAs were investigated for enrichment in CNVs associated with schizophrenia. Significant enrichment at p < 0.05 (grey line) shown in red (c,f). (g–i) Changes in the transcriptome were measured in the fetal cortex of offspring exposed to gestational normoxia or hypoxia and maternal administration of saline or MitoQ-NPs. Log2-fold changes of significant differentially expressed genes under hypoxia alone (blue) or hypoxia plus MitoQ-NP application (orange), relative to control levels (normoxia + saline) are shown (g). Significantly enriched biological processes of differentially expressed genes; the grey bars represent number of proteins assigned to each gene ontology term and the black bars show the respective p value (h). Correlation of miR-17-5p abundance changes in fetal plasma with expression changes of the gene coding for Ribosome protein L10-like (RPL10L) in fetal brain, under Normoxia + Saline (NS) and Hypoxia + Saline (HS) conditions (i). Log-transformed counts are shown. p value was adjusted for multiple comparisons using Benjamini-Hochberg.