Abstract
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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Acknowledgement
We extend our gratitude to the NASA staff, particularly Lisa Baer, Dr. Charles Wade, and Dr. April Ronca of National Aeronautics and Space Administration (NASA) Ames Research Center for their expert help with running the experiment. We are grateful to Karl Dykema, Kyle Furge and Jim Liesman for their help with statistical analysis.
Financial support
This work was supported by NASA grant NNA05CP91A.
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The numerical fold-change and P value for genes associated with solute transport, TCA cycle and fatty acid metabolism across adipose, liver and mammary tissues during the pregnancy to lactation transition. (DOC 59 kb)
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Patel, O.V., Casey, T., Dover, H. et al. Homeorhetic adaptation to lactation: comparative transcriptome analysis of mammary, liver, and adipose tissue during the transition from pregnancy to lactation in rats. Funct Integr Genomics 11, 193–202 (2011). https://doi.org/10.1007/s10142-010-0193-0
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DOI: https://doi.org/10.1007/s10142-010-0193-0