Transcriptomic Analysis of Plac1 Ablation Reveals Broad Alterations in Signaling Pathways Essential for Prenatal Development and Overlap with a Preeclampsia-Associated Signature

Plac1 is an X-linked gene essential for placental and embryonic development. A knockout (KO) mouse model was used to define placental gene expression changes associated with Plac1 loss at E16.5 and E18.5 using gene expression microarray. Genes exhibiting at least a 1.5-fold change and FDR < 0.05 were considered significant. At E16.5, 717 genes were downregulated and 796 upregulated in KO placentas relative to wild type (WT), whereas at E18.5, 1121 genes were downregulated and 1151 upregulated. Subsets of highly and uniquely dysregulated genes were examined by gene-level curation alongside systems-level analyses, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Ingenuity Pathway Analysis (IPA), applied to the full differentially expressed gene (DEG) datasets. Downregulated genes were enriched for Rho GTPase-mediated and actin cytoskeleton-based processes, as well as membrane-associated signaling pathways with established roles in placental and embryonic development, vascular function, and branching morphogenesis. Overlap with pathways and molecular features associated with preeclampsia was also observed. In contrast, upregulated genes reflected, in part, immune activation and oxidative stress responses. These findings represent an important exploratory, hypothesis-generating analysis and provide a biologically coherent framework for understanding how Plac1 loss may be associated with placental dysfunction and pregnancy-related disease.