Project description:In comparison with cow milk, goat (Capra hircus) milk contains much higher levels of unsaturated fatty acids, as well as higher levels of total fat, proteins, carbohydrates, calcium, and vitamins.The main objective of the present study was to better define the relationship of known miRNAs regulating milk fat metabolism. Our main purpose is to search for some known miRNAs regulating milk fat metabolism, to this end, we screened potential miRNAs with differential expression between peak-lactation and non-lactation.
Project description:Dynamic transcriptome profiles in yak mammary gland were evaluated by sampling mammary tissue at -30, -15, 1, 15, 30, 60, 120, 180 and 240 d relative to parturition and using a bovine commercial microarray platform. Several bioinformatics tools were used to analyze the data, both as expression relative to -30 d and as expression relative to the previous time point. There were >6,000 differentially expressed transcript (DEG; FDR<0.05; P<0.05) throughout lactation with larger DEG observed at the onset (1 vs. -15d) and at the end of lactation (240 vs. 180d). Bioinformatics analysis allowed to identify lactation-related genes on yak chromosomes which laid the foundation for determination of QTL location. Among most-impacted bovine chromosomes (BTA), BTA6, BTA9 and BTA28 were induced while BTA3, BTA4 and BTA14 were inhibited throughout lactation. Functional analysis underlined an overall induction of lipid metabolism, suggesting increases in triglycerides synthesis likely regulated by PPAR signaling. Data suggested induction of amino acid metabolism while increasing secretion or protein, but decreasing proteasome, indicating a major role of amino acid handling and reduced protein degradation in the synthesis and secretion of milk proteins. Glycan biosynthesis, both for N-glycan and O-glycan, was induced suggesting increased glycan content in milk. Cell cycle and immune response, especially antigen processing and presentation, were strongly inhibited during lactation suggesting morphological changes were minimized while the mammary gland prevents immune hyper responses during lactation. Transcripts associated with response to radiation and low oxygen were enriched in the down-regulated DEG affected by stage of lactation. Except for the latter, functions affected by the transcriptomic adaptation to lactation in mammary tissue of yak were very similar to the ones observed in dairy cows.
Project description:Macrophages are involved in immune defense, organogenesis and tissue homeostasis. They also contribute to the different phases of mammary gland remodeling during development, pregnancy and involution post-lactation. Yet, less is known about the dynamics of mammary gland macrophages in the lactation stage. Here, we describe a macrophage population present during lactation in mice. By multi-parameter flow cytometry and single-cell RNA sequencing we reveal this population as distinct from the two resident macrophage subsets present pregestationally. These lactation-induced macrophages (LiMacs) are predominantly monocyte-derived and expand by proliferation in situ concomitant with nursing. LiMacs develop independently of IL-34 but require CSF-1 signaling and are partly microbiota-dependent. Locally, they reside adjacent to the basal cells of the alveoli and extravasate into the milk. Moreover, we also found several macrophage subsets in human milk, resembling LiMacs. Collectively, these findings reveal the emergence of unique macrophages in the mammary gland and milk during lactation.
Project description:We have previously shown that during lactation, osteocytes directly remodel their perilacunar and pericanalicular matrix, thereby mobilizing calcium and contributing to maternal bone loss. To identify genes potentially responsible for perilacunar remodeling, microarray analysis was performed on osteocytes from CD-1 virgin and lactating mice and mice sacrificed on day 7 post weaning. By comparing how gene expression changes in osteocytes among virgin, lactation and post lactation, the goal is to identify the genes osteocytes use to remodel their perilacunar matrix
Project description:In comparison with cow milk, goat (Capra hircus) milk contains much higher levels of unsaturated fatty acids, as well as higher levels of total fat, proteins, carbohydrates, calcium, and vitamins.The main objective of the present study was to better define the relationship of known miRNAs regulating milk fat metabolism. Our main purpose is to search for some known miRNAs regulating milk fat metabolism, to this end, we screened potential miRNAs with differential expression between peak-lactation and non-lactation. qPCR gene expression profiling. Monocytes from three healthy goats (3 year old) of similar body weight. We screened a series of potential miRNAs involved in regulation of milk metabolism.
Project description:Human infants are born to breastfeed. While 50% of lactating persons report struggling to make enough milk, there are no governmentally-approved drugs to enhance lactation1. Here, we engineer a variant of the naturally-occurring driver of lactation, the hormone Prolactin, to increase its serum half-life and produce a viable drug candidate. Our engineered variant,Prolactin-eXtra Long-acting(Prolactin-XL), is comprised of endogenously active human prolactin fused to an engineered human IgG1 Fc domain designed to overcome the unique drug development challenges specific to the lactating person-infant dyad. Our Prolactin-XL has a serum half-life of 70.9h in mice, 2,625-fold longer than endogenously active prolactin alone (70.9h v. 0.027h). We demonstrate that Prolactin-XL increases milk production and restores growth of pups fed by dams with pharmacologically-ablated lactation. We show that Prolactin-XL-enhanced lactation is accompanied by reversible, alveolar cell-driven changes in mammary gland morphology. Prolactin-XL treatment was associated with no identifiable pathology or adverse side effect in the lactating mice or nursing pups. This work establishes long-acting prolactins as a potentially powerful pharmacologic means to combat insufficient lactation. Implications for future research in lactating mammary gland biology and a potential preclinical path for developing Prolactin-XL for use in lactating persons are discussed.
Project description:Progestin secretion increases remarkably during pregnancy and lactation. To explore how prolactin affect tumor growth, we used microarray to detailed the different expressed genes between lactation mice and ctrl mice.
Project description:16 rats were mated and the dams continued pregnancy (controls) or were subsequently caloric restricted (CR) for 20% during days 1-12. Control female/male offspring continued normal lactation, while offspring of CR-treated dams received either normal lactation (CR group) or received during lactation until PN21 leptin supplementation. Leptin treatment of offspring during lactation after caloric restriction of dams during pregnancy reverts CR-induced dysfunction.
Project description:Previoulsly miRNA expression profiling of the whole mammary gland across different stages of pregnancy and lactation has been performed in mice. Since mammary gland has both epithelial and stromal compartments, to specifically identify the miRNAs involved in the transition from pregnancy to lactation a process termed as secretory activation, expression profiling of isolated mammary epithelial cells (MECs) from four CD1 mice each at Pregnancy day 14 (P14) and Lactation day 2 (L2) was performed in the current study. Statistical analysis of the miRNA changes between P14 and L2 identified 32 miRNAs to be differentially expressed with a fold change greater than or equal to 2, of which, the majority of them declinied at the onset of lactation.