Hepatic Gene Expression during the Perinatal Transition in the Rat

During the immediate postnatal period, the liver, with its role in energy metabolism and macromolecule synthesis, plays a central role in the perinatal transition. Using RNA microarrays and several complementary computational analyses, we characterized changes in hepatic gene expression in the rat across a developmental period starting with the late gestation fetus (embryonic day 21), and including 30 min postnatal (PN), 4 hr PN, 12 hr PN, 1 day PN and 1 week after birth. Following subtle changes in gene expression at the earliest postnatal time point, there were marked changes that occurred between 4 hr and 12 hr after birth. These reflected changes in multiple metabolic pathways, with expression of enzymes involved in glycolysis and cholesterol synthesis showing the greatest change. Over 50% of nuclear-encoded mitochondrial genes changed in the first 7 days of postnatal life, with 25% changing within the first 24 hr. We also observed changes coinciding with a transient period of synchronous hepatocyte proliferation that we had observed previously, which occurs during the first postnatal week. Analysis for upstream regulators of gene expression indicated multiple initiating factors, including cell stress, hormones and cytokines. Also implicated were multiple canonical transcription factor networks. We conclude that changes in gene expression during the early phases of the perinatal transition involve a complex, choreographed network of signaling pathways that respond to a variety of environmental stimuli. This transcriptomic response during the immediate postnatal period reflects a complex metabolic adaptive response that incorporates a panoply of signaling pathways and transcriptional regulators. Term (E21) and early postnatal (30 min, 4hr, 12hr, 1day and 7 day after birth) liver was harvested from triplicate dams. RNA was isolated using the Rneasy kit. Affymetrix Rat transcriptome 1.0 arrays were used.