Article

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: 2.69). 03/2011; 11(1):193-202. DOI: 10.1007/s10142-010-0193-0
Source: PubMed

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.

1 Follower
 · 
119 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A combined analysis of a bovine and ovine mammary gland transcriptome from two similarly designed microarray experiments suggested a strong positive association between the differentially expressed genes (DEGs) implying that major pathways regulating the lactation process were evolutionarily conserved within the two species. Some distinct pathways identified indicate the physiological differences underlying the species. Novel techniques were established for the combined analysis of the transcriptomes of different species or heterogeneous platforms for comparative gene expression analysis allowing for greater experimental power to detect conserved pathways. Conserved DEGs were mainly related to lipid metabolism, amino acid synthesis, cell proliferation, signaling and immune systems indicating functional processes involved in the regulation of lactation including milk synthesis and lactation persistency. There were no functionally annotated DEGs that show antagonistic expression between sheep and cattle suggesting that the lactation process is essentially the same in the two species. DEGs that were found exclusively in sheep were mostly associated with gland morphogenesis while DEGs exclusively expressed in cattle, indicated that certain immune response and milk composition mechanisms were different in the bovine as compared to sheep. The conserved processes across the two species suggest the use of the ovine as a suitable model for lactation studies, considering the challenges and expense of conducting lactation physiology and genomics studies within the cow.
    Functional & Integrative Genomics 01/2013; 13(1). DOI:10.1007/s10142-012-0307-y · 2.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Altered gravity load induced by spaceflight (microgravity) and centrifugation (hypergravity) is associated with changes in circadian, metabolic, and reproductive systems. Exposure to 2-g hypergravity (HG) during pregnancy and lactation decreased rate of mammary metabolic activity and increased pup mortality. We hypothesize HG disrupted maternal homeorhetic responses to pregnancy and lactation are due to changes in maternal metabolism, hormone concentrations, and maternal behavior related to gravity induced alterations in circadian clocks. Effect of HG exposure on mammary, liver and adipose tissue metabolism, plasma hormones and maternal behavior were analyzed in rat dams from mid-pregnancy (Gestational day [G]11) through early lactation (Postnatal day [P]3); comparisons were made across five time-points: G20, G21, P0 (labor and delivery), P1 and P3. Blood, mammary, liver, and adipose tissue were collected for analyzing plasma hormones, glucose oxidation to CO(2) and incorporation into lipids, or gene expression. Maternal behavioral phenotyping was conducted using time-lapse videographic analyses. Dam and fetal-pup body mass were significantly reduced in HG in all age groups. HG did not affect labor and delivery; however, HG pups experienced a greater rate of mortality. PRL, corticosterone, and insulin levels and receptor genes were altered by HG. Mammary, liver and adipose tissue metabolism and expression of genes that regulate lipid metabolism were altered by HG exposure. Exposure to HG significantly changed expression of core clock genes in mammary and liver and circadian rhythms of maternal behavior. Gravity load alterations in dam's circadian system may have impacted homeorhetic adaptations needed for a successful lactation.
    06/2012; 1(6):570-81. DOI:10.1242/bio.2012687
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In tsetse flies, nutrients for intrauterine larval development are synthesized by the modified accessory gland (milk gland) and provided in mother's milk during lactation. Interference with at least two milk proteins has been shown to extend larval development and reduce fecundity. The goal of this study was to perform a comprehensive characterization of tsetse milk proteins using lactation-specific transcriptome/milk proteome analyses and to define functional role(s) for the milk proteins during lactation. Differential analysis of RNA-seq data from lactating and dry (non-lactating) females revealed enrichment of transcripts coding for protein synthesis machinery, lipid metabolism and secretory proteins during lactation. Among the genes induced during lactation were those encoding the previously identified milk proteins (milk gland proteins 1-3, transferrin and acid sphingomyelinase 1) and seven new genes (mgp4-10). The genes encoding mgp2-10 are organized on a 40 kb syntenic block in the tsetse genome, have similar exon-intron arrangements, and share regions of amino acid sequence similarity. Expression of mgp2-10 is female-specific and high during milk secretion. While knockdown of a single mgp failed to reduce fecundity, simultaneous knockdown of multiple variants reduced milk protein levels and lowered fecundity. The genomic localization, gene structure similarities, and functional redundancy of MGP2-10 suggest that they constitute a novel highly divergent protein family. Our data indicates that MGP2-10 function both as the primary amino acid resource for the developing larva and in the maintenance of milk homeostasis, similar to the function of the mammalian casein family of milk proteins. This study underscores the dynamic nature of the lactation cycle and identifies a novel family of lactation-specific proteins, unique to Glossina sp., that are essential to larval development. The specificity of MGP2-10 to tsetse and their critical role during lactation suggests that these proteins may be an excellent target for tsetse-specific population control approaches.
    PLoS Genetics 04/2014; 10(4):e1003874. DOI:10.1371/journal.pgen.1003874 · 8.17 Impact Factor

Full-text

Download
33 Downloads
Available from
May 23, 2014