A bioinformatic approach to investigate placental and fetal gene expression during diabetic stress in pregnancy

Maternal diabetes disturbs the intrauterine environment and poses significant risk to fetal development, yet the molecular responses of placental and fetal tissues to diabetic stress remain incompletely characterized. We applied a comparative bioinformatic framework to two publicly available microarray datasets representing placental/decidua and fetal tissue collected at embryonic day 10.5. Both datasets were processed using RMA normalization, differential gene expression analysis, principal component analysis, functional enrichment analysis, and Pathview pathway visualization in R. Placental/decidual exhibited a comparatively constrained differential-expression profile with only two probes reaching BH-adjusted p < 0.05 and one probe meeting both BH-adjusted p < 0.05 and |log2FC| > 1. Rank-based GSEA across the complete gene-ranking distribution was used to identify coordinated pathway-level changes. This analysis identified enrichment of gene programs involving ribosome biogenesis, RNA processing and splicing, cell-cycle and DNA-replication processes, and oxidative phosphorylation. In contrast, fetal tissue exhibited substantially broader differential expression with 2,306 probes meeting both BH-adjusted p < 0.05 and |log2FC| > 1. KEGG over-representation analysis identified 62 significantly enriched pathways, including pathways associated with axon guidance, Wnt signaling, focal adhesion, MAPK signaling, and PI3K-AKT signaling. Pathview mapping further demonstrated a broader distribution of transcript-level alterations across fetal signaling components compared with the comparatively localized changes observed in placental/decidual tissue. These findings demonstrate distinct transcriptional responses between placental/decidual and fetal tissue under diabetic stress. The comparatively constrained placental/decidual differential-expression profile together with broader fetal transcriptional alterations is consistent with a model in which the maternal-fetal interface may modulate responses to diabetic stress. Collectively, this comparative analysis identified coordinated molecular processes associated with diabetic pregnancy and provides a framework for early biomarker development in diabetic pregnancies.