Key stages in mammary gland development.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE8191 | GEO | 2007/06/21
SECONDARY ACCESSION(S): PRJNA101097
REPOSITORIES: GEO
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Project description:The transition from pregnancy to lactation is a critical event in the survival of the newborn since all the nutrient requirements of the infant are provided by milk. While milk contains numerous components, including proteins, that aid in maintaining the health of the infant, lactose and milk fat represent the critical energy providing elements of milk. Much of the research to date on mammary epithelial differentiation has focused upon expression of milk protein genes, providing a somewhat distorted view of alveolar differentiation and secretory activation. While expression of milk protein genes increases during pregnancy and at secretory activation, the genes whose expression is more tightly regulated at this transition are those that regulate lipid biosynthesis. The sterol regulatory element binding protein (SREBP) family of transcription factors is recognized as regulating fatty acid and cholesterol biosynthesis. We propose that SREBP1 is a critical regulator of secretory activation with regard to lipid biosynthesis, in a manner that responds to diet, and that the serine/threonine protein kinase Akt influences this process, resulting in a highly efficient lipid synthetic organ that is able to support the nutritional needs of the newborn. Experiment Overall Design: Key points are examined in a time series of FVB mouse mammary gland development, secretory activation, lactation and involution. Quadruplicate mice (four biological replicates) at each time point were used for statistical power totalling 40 individual arrays in this study. Mice were as staged pregnant day 1 the day that post coital plug was observed, and similarly, lactation day 1 was the first day after birth. Involution day 2 is a forced weening model, where day 9 lactating dams had their litters removed for two days and then the dams were killed.
2008-11-06 | E-GEOD-8191 | biostudies-arrayexpress
Project description:We profiled differential gene expression in vivo between pregnant day 14 (secretory differentiation) and lactation day 4 (established secretory activation) using isolated mouse mammary epithelial cells depleted of the mammary adipocytes. Liver-X-Receptors are ligand-dependent transcription factors activated by cholesterol metabolites. These receptors induce a suite of target genes required for de novo synthesis of triglycerides and cholesterol transport in many tissues. Two different isoforms -LXRα and LXRβ- have been well characterized in liver, adipocytes, macrophages and intestinal epithelium among others, but their contribution to cholesterol and fatty acid efflux in the lactating mammary gland is poorly understood. We hypothesize that LXR regulates lipogenesis during milk fat production in lactation. Global mRNA analysis of mouse mammary epithelial cells (MECs) revealed multiple LXR/RXR targets are upregulated sharply at the onset of lactation compared to mid-pregnancy. LXRα is the primary isoform and its protein levels increase throughout lactation in MECs. The LXR agonist GW3965 markedly induced several genes involved in cholesterol transport and lipogenesis and enhanced cytoplasmic lipid droplet accumulation in the HC11 MEC cell line. Importantly, in vivo pharmacological activation of LXR increased the milk cholesterol percentage and induced Srebp1c and Abca7 expression in MECs. Cumulatively, our findings identify LXRα as an important regulator of cholesterol incorporation into the milk through key nodes of de novo lipogenesis, suggesting a potential therapeutic target in women with difficulty initiating lactation.
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Project description:Breast milk is the primary source of nutrition for newborns, and rich in immunological components. microRNAs (miRNAs), a well-defined group of non-coding small RNAs, are present in various body fluids (such as breast milk), which are selectively packaged inside the exosomes, a type of membrane vesicles, secreted by most cell types. These exosomal miRNAs could be actively delivered into recipient cells, and regulate target gene expression and recipient cell function. We present the lactation-related miRNA expression profiles in porcine milk exosomes across entire lactation period in pig industry (newborn to 28 days after birth) using deep sequencing technology. We found that the immune-related miRNAs are presented and enriched in breast milk exosomes, and generally resistant to relatively harsh conditions. Notably, these exosomal miRNAs exhibited the higher abundances in the colostrum (newborn to 3 days after birth) than that in the mature milk (7 to 28 days after birth), as well as in the serum of colostrum-feeding piglets compared with the only mature milk-feeding piglets. These immune-related miRNAs-loaded exosomes in breast milk may be transferred into the infant body via the digestive tract. These observations are prelude to the in-depth investigations of the essential roles of the breast milk in the development of the infant’s immune system. Eight small RNA libraries in porcine breast milk exosomes of six lactigenous stages (0, 3, 7, 14, 21 and 28 days after birth) from three female pigs were sequenced.
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Project description:Development of mammary secretory epithelium and its functional differentiation occur during pregnancy under combined actions of ovarian steroids, pituitary hormones and growth factors. If the effect of these molecules is relatively well known, effect of differentiation factors expressed locally is not enough characterized. To understand local regulation of mammary tissue development and differentiation we realized transcriptional analysis on 5 physiological stages (4 during pregnancy and 1 during lactation). An appropriate experimental design was drawn to follow gene expression profiles during differentiation of mammary tissue. Results showed that at mid-pregnancy, mammary tissue was enough defferentiated into secretory epithelium to express milk protein genes and genes of the immune response system actors. But the secretoty activation of mammary epithelium was done only after parturition and wwas characterized by the expression of lipidogenesis genes. Keywords: time course, mammary gland differentiation, goat, pregnancy 18 samples, loop design
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Project description:Human milk is the truest form of personalized nutrition, supporting dynamic needs of the infant with important nutritional and bioactive constituents that change throughout lactation. Additionally, human milk is individual specific and is unique for each mother-infant dyad. Proteins and endogenous peptides are 2 key classes of major human milk components making up the proteome, each with unique and synergistic functionality, working to provide protection for the healthy development of infants. Our objective was to comprehensively characterize and quantify the human milk proteome for varying early life challenges. We assessed in-depth individual variations of the human milk proteome across lactation, by mass spectrometry. Finding that the human milk proteome showed continuous and gradual changes over lactation, and that inflammatory events correlated with a strong and rapid change in the composition of human milk proteins and peptides. Personalized human milk profiling resulted in the systematic annotation of the milk proteome, and elucidated how early onset inflammatory events can lead to infant immune training from human milk.
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Project description:Development of mammary secretory epithelium and its functional differentiation occur during pregnancy under combined actions of ovarian steroids, pituitary hormones and growth factors. If the effect of these molecules is relatively well known, effect of differentiation factors expressed locally is not enough characterized. To understand local regulation of mammary tissue development and differentiation we realized transcriptional analysis on 5 physiological stages (4 during pregnancy and 1 during lactation). An appropriate experimental design was drawn to follow gene expression profiles during differentiation of mammary tissue. Results showed that at mid-pregnancy, mammary tissue was enough defferentiated into secretory epithelium to express milk protein genes and genes of the immune response system actors. But the secretoty activation of mammary epithelium was done only after parturition and wwas characterized by the expression of lipidogenesis genes. Keywords: time course, mammary gland differentiation, goat, pregnancy
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