Abstract
Cyp1b1 substantially affects hepatic vascular and stellate cells (HSC) with linkage to liver fibrosis. Despite minimal hepatocyte expression, Cyp1b1 deletion substantially impacts liver gene expression at birth and weaning. The appreciable Cyp1b1 expression in surrounding embryo mesenchyme, during early organogenesis, provides a likely source for Cyp1b1. Here defined breeder diets established major interconnected effects on neonatal liver of α-linolenic acid (ALA), vitamin A deficiency (VAD) and suboptimal iron fed mice. At birth Cyp1b1 deletion and VAD each activated perinatal HSC, while suppressing iron control by hepcidin. Cyp1b1 deletion also advanced the expression of diverse genes linked to iron regulation. Postnatal stimulations of Srebp-regulated genes in the fatty acid and cholesterol biosynthesis pathways were suppressed by Cyp1b1-deficiency. LncRNA H19 and the neutrophil alarmin S100a9 expression increased due to slower postnatal decline with Cyp1b1 deficiency. VAD reversed each of Cyp1b1 effect, probably due to enhanced HSC release of Apo-Rbp4. At birth, Cyp1b1 deletion enhanced H19 participation. Notably, a suppressor (Cnot3) decreased while an activity partner (Ezh2/H3K methylation) increased H19 expression. ALA elevated hepcidin mRNA and countered the inhibitory effects of Cyp1b1 deletion on hepcidin expression. Oxylipin metabolites of ALA from highly expressed hepatic Cyps are potential mediators. Cyp expression patterns demonstrated female dimorphism for neonatal liver. Mothers followed one of three fetal growth support programs probably linked to maturity at conception.