Mammary gland metabolism and its relevance to the fetoplacental expression of cytokine signaling in caveolin-1 null mice

Mice lacking caveolin-1 (<i>Cav1</i>), a major protein of the lipid raft of plasma membrane, show deregulated cellular proliferation of the mammary gland and an abnormal fetoplacental communication during pregnancy. This study leverages a multi-omics approach to test the hypothesis that the absence of <i>Cav1</i> elicits a coordinated crosstalk of genes among the mammary gland, placenta and fetal brain in pregnant mice. Integrative analysis of metabolomics and transcriptomics data of mammary glands showed that the loss of <i>Cav1</i> significantly impacted specific metabolites and metabolic pathways in the pregnant mice. Next, gene expression changes of the deregulated metabolic pathways of the mammary gland were compared with the gene expression changes of the placenta and fetus. The analysis showed that genes associated with specific metabolic and signaling pathways changed in a coordinated manner in the placenta, mammary gland and fetal brain of <i>Cav1</i>-null mice. The cytokine signaling pathway emerged as a key player of the molecular crosstalk among these tissues. By interrogating the single-nuclei gene expression data of placenta and fetal brain previously generated from <i>Cav1</i>-null mice, the study further revealed that these metabolic and signaling genes were differentially regulated in specific cell types of the placenta and fetal brain. Though a causal effect of the mammary gland on the placenta and/or fetal brain can't be inferred from this study, the findings show that the mammary gland, placenta and fetal brain show a coordinated molecular crosstalk in response to the absence of <i>Cav1</i> in mice.