Homeorhetic adaptation to lactation: Comparative transcriptome analysis of mammary, liver, and adipose tissue during the transition from pregnancy to lactation in rats

Department of Cell and Molecular Biology, Grand Valley State University, Allendale, MI 49401, USA.
Functional & Integrative Genomics (Impact Factor: 2.48). 03/2011; 11(1):193-202. DOI: 10.1007/s10142-010-0193-0
Source: PubMed


Tissue-specific shifts in a dam's metabolism to support fetal and neonatal growth during pregnancy and lactation are controlled by differential expression of regulatory genes. The goal of this study was to identify a more detailed cohort of genes in mammary, liver, and adipose tissue that are transcriptionally controlled during the pregnancy to lactation evolution and explore the relationship of these genes to core clock genes. Total RNA was isolated from mammary, liver and adipose tissues collected from rat dams on day 20 of pregnancy (P20) and day 1 of lactation (L1) and gene expression was measured using Rat 230 2.0 Affymetrix GeneChips. Gene functional analysis revealed that pathway associated metabolism (carbohydrate, amino acid, lipid, cholesterol, protein) were enriched (P < 0.001) in the mammary gland during P20 to L1 transition. Approximately 50% of the genes associated with solute transport, as well as lipogenesis were up-regulated in the mammary gland during P20 to L1 transition compared to 10% in liver and 15% in adipose tissue. Genes engaged in conveying glucose (INSR, GLUT1, GLUT4, SGLT1, and SGLT2), bicarbonate (SLC4), sodium (SLC9), zinc (SLC30), copper (SLC31), iron (SLC40) in tandem with rate-limiting lipogenic genes (ACACA, FASN, PRLR, SREBP2, THRSP) were specifically enriched in the mammary gland during the P20 to L1 evolution. Our results provide insight into a cross-tissue transcriptional repertoire that is associated with homeorhetic adaptation needed to support lactation, and at the onset of lactation the mammary gland becomes a factory for macromolecular biosynthesis through inducing genes participating in nutrient transfer and lipid biosynthesis.

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Available from: Theresa Casey, Mar 20, 2014
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    • "No comparison between the two species has been reported so far, for the physiology of different stages of lactation. Detailed studies have been performed to examine gene expression in the mammary gland during puberty, pregnancy, lactation and involution in mouse (Lemkin et al. 2000; Master et al. 2002; Clarkson et al. 2004; Stein et al. 2005; Wessel et al. 2006; Rudolph et al. 2007; Lemay et al. 2009; Loor and Cohick 2009; Patel et al. 2011) and cow (Ron et al. 2007; Piantoni et al. 2010; Bionaz et al. 2012). Using the genome of a platypus, opossum, bovine, human, dog, mice and rat, gene loss and duplication, phylogeny, sequence conservation, and evolution have been examined focusing on the milk and mammary genes (Lemay et al. 2009). "
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    • "Thus to insure adequate milk production and simultaneously maintain maternal homeostasis, the lactating dam utilizes homeorhetic processes to shift her metabolism. The dam's normal homeorhetic response to the increased nutrient and energy demands of milk synthesis were mediated in part by global changes in gene transcription in mammary, liver and adipose including changes in clock genes that regulate circadian rhythms (Casey et al., 2009; Patel et al., 2011). Changes in molecular clocks during the transition from pregnancy to lactation in relation to other transcriptional profiles of mammary, liver and adipose tissues suggested that homeorhetic adaptation to lactation may be by coordinated in part by the circadian system. "
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