Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk.
Ontology highlight
ABSTRACT:
SUBMITTER: Alsaweed M
PROVIDER: S-EPMC4745068 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
Publications
Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk.
Alsaweed Mohammed M Lai Ching Tat CT Hartmann Peter E PE Geddes Donna T DT Kakulas Foteini F
Scientific reports 20160208
Human milk (HM) contains regulatory biomolecules including miRNAs, the origin and functional significance of which are still undetermined. We used TaqMan OpenArrays to profile 681 mature miRNAs in HM cells and fat, and compared them with maternal peripheral blood mononuclear cells (PBMCs) and plasma, and bovine and soy infant formulae. HM cells and PBMCs (292 and 345 miRNAs, respectively) had higher miRNA content than HM fat and plasma (242 and 219 miRNAs, respectively) (p < 0.05). A strong asso ...[more]
Similar Datasets
Project description:Human milk (HM) contains an array of regulatory biomolecules including miRNAs, the origin, properties, distribution and functional significance of which are still undetermined. In this study, we used the TaqMan OpenArray System to profile 681 human mature miRNAs in two fractions of HM (cells and lipids) collected from healthy mothers in month 2 of lactation (n=10). Comparisons were performed with maternal peripheral blood mononuclear cells (PBMCs) and plasma collected from the same individuals, as well as with a bovine- and a soy-based infant formulae. HM cells (292 miRNAs) and PBMCs (345 miRNAs) had higher miRNA content than HM lipids (242 miRNAs) and plasma (219 miRNAs), respectively (p<0.05). Despite the wide variation in miRNA profiles and expression between mothers, a strong association was found between HM cells and lipids within a mother, whilst PBMCs and plasma were distinctly different to the two milk fractions, with plasma displaying marked inter-individual variation. Considering the dominance of epithelial cells in mature milk of healthy women, these results suggest that HM cell and lipid miRNAs primarily originate from the mammary epithelium, whilst the maternal circulation may have a smaller contribution. Infant formulae contained very few human miRNA compared to HM. Our findings demonstrate that unlike infant formulae, human milk is a rich source of lactation-specific miRNA, which could be used as a biomarker of the performance and health status of the lactating gland. Given the recently identified stability and gene regulatory functions of food-derived miRNAs, HM miRNAs may contribute to infant protection and development.
2015-03-30 | GSE66358 | GEO
Project description:Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk
| PRJNA276637 | ENA
Project description:Considering the importance of early disease detection for reducing the huge financial and animal welfare impact of bovine mastitis globally, improved tools are urgently needed that can accurately detect early mammary inflammation. MiRNAs have demonstrated value as disease biomarkers, however, their potential for accurately detecting early mammary inflammation has not been examined in detail. To address this, we investigated the association between levels of four inflammation-associated miRNAs (bta-miR-26a, bta-miR-142-5p, bta-miR-146a and bta-miR-223) and CMT scores (0 to 3) obtained from a large number of individual quarter milk samples (n = 236) collected from dairy cows at different lactations (1 to 4). Initial analyses (n = 21 samples) confirmed that the levels of each of bta-miR-142-5p, bta-miR-146a and bta-miR-223 in whole milk were significantly correlated with mRNA levels of known inflammatory markers (HP, TNF, CXCL8 and IL1B) in milk cells (Rho ≥ 0.49, P < 0.005). Subsequent analyses (n = 215 samples) revealed a significant effect of CMT score on each of the four miRNAs analysed (P < 0.0001), characterised by a progressive increase in miRNA levels in milk as CMT score increase from 0 to > 1. Moreover, a significant effect of lactation number (P < 0.01) for bta-miR-26a, bta-miR-142-5p and bta-miR-146a was attributed to higher miRNA levels during lactation 1 than later lactations. Finally, by generating ROC curves we showed that bta-miR-223 and bta-miR-142-5p levels could identify early inflammatory changes in individual quarter milk samples (CMT1) with high accuracy (100% sensitivity, > 81% specificity). Our results provide novel proof of the value of miRNAs as early diagnostic biomarkers of bovine mastitis.
| S-EPMC8948199 | biostudies-literature
Project description:Mammary gland morphology varies considerably between pregnancy and lactation status, e.g., virgin to pregnant and lactation to weaning. Throughout these critical developmental phases, the mammary glands undergo remodeling to accommodate changes in milk production capacity, which is positively correlated with milk protein expression. The purpose of this study was to investigate the microRNA (miRNA) expression profiles in female ICR mice's mammary glands at the virgin stage (V), day 16 of pregnancy (P16d), day 12 of lactation (L12d), day 1 of forced weaning (FW1d), and day 3 of forced weaning (FW3d), and to identify the miRNAs regulating milk protein gene expression. During the five stages of testing, 852 known miRNAs and 179 novel miRNAs were identified in the mammary glands. Based on their expression patterns, the identified miRNAs were grouped into 12 clusters. The expression pattern of cluster 1 miRNAs was opposite to that of milk protein genes in mammary glands in all five different stages. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the predicted target genes of cluster 1 miRNAs were related to murine mammary gland development and lactation. Furthermore, fluorescence in situ hybridization (FISH) analysis revealed that the novel-mmu-miR424-5p, which belongs to the cluster 1 miRNAs, was expressed in murine mammary epithelial cells. The dual-luciferase reporter assay revealed that an important milk protein gene-β-casein (CSN2)-was regarded as one of the likely targets for the novel-mmu-miR424-5p. This study analyzed the expression patterns of miRNAs in murine mammary glands throughout five critical developmental stages, and discovered a novel miRNA involved in regulating the expression of CSN2. These findings contribute to an enhanced understanding of the developmental biology of mammary glands, providing guidelines for increasing lactation efficiency and milk quality.
| S-EPMC8944794 | biostudies-literature
Project description:The mammary gland is composed of a complex cellular hierarchy with unusual postnatal plasticity. The identities of stem/progenitor cell populations, as well as tumour-initiating cells that give rise to breast cancer, are incompletely understood. Here we show that Lgr6 marks rare populations of cells in both basal and luminal mammary gland compartments in mice. Lineage tracing analysis showed that Lgr6+ cells are unipotent progenitors, which expand clonally during puberty but diminish in adulthood. In pregnancy or following stimulation with ovarian hormones, adult Lgr6+ cells regained proliferative potency and their progeny formed alveoli over repeated pregnancies. Oncogenic mutations in Lgr6+ cells resulted in expansion of luminal cells, culminating in mammary gland tumours. Conversely, depletion of Lgr6+ cells in the MMTV-PyMT model of mammary tumorigenesis significantly impaired tumour growth. Thus, Lgr6 marks mammary gland progenitor cells that can initiate tumours, and cells of luminal breast tumours required for efficient tumour maintenance.
| S-EPMC5812439 | biostudies-literature
Project description:Previous work demonstrates that proteases present in human milk release hundreds of peptides derived from milk proteins. However, the question of whether human milk protein digestion begins within the mammary gland remains incompletely answered. The primary objective of this study was to determine whether proteolytic degradation of human milk proteins into peptides begins within the mammary gland. The secondary objectives were to determine which milk proteases participate in the proteolysis and to predict which released peptides have bioactivity. Lactating mothers (n = 4) expressed their milk directly into a mixture of antiproteases on ice followed by immediate freezing of the milk to limit post-expression protease activity. Samples were analyzed for their peptide profiles via mass spectrometry and database searching. Peptidomics-based protease prediction and bioactivity prediction were each performed with several different approaches. The findings demonstrate that human milk contains more than 1,100 unique peptides derived from milk protein hydrolysis within the mammary gland. These peptides derived from 42 milk proteins and included 306 potential bioactive peptides. Based on the peptidomics data, plasmin was predicted to be the milk protease most active in the hydrolysis of human milk proteins within the mammary gland. Milk proteases actively cleave milk proteins within the mammary gland, initiating the release of functional peptides. Thus, the directly breastfed infant receives partially pre-digested proteins and numerous bioactive peptides.
| S-EPMC5856648 | biostudies-literature
Project description:As the only nutritional source for newborn piglets, porcine colostrum and milk contain critical nutritional and immunological components including carbohydrates, lipids, and proteins (immunoglobulins). However, porcine milk composition is more complex than these three components. Recently, scientists identified additional and novel components of sow colostrum and milk, including exosomes, oligosaccharides, and bacteria, which possibly act as biological signals and modulate the intestinal environment and immune status in piglets and later in life. Evaluation of these nutritional and non-nutritional components in porcine milk will help better understand the nutritional and biological function of porcine colostrum and milk. Furthermore, some important functions of the porcine mammary gland have been reported in recent published literature. These preliminary studies hypothesized how glucose, amino acids, and fatty acids are transported from maternal blood to the porcine mammary gland for milk synthesis. Therefore, we summarized recent reports on sow milk composition and porcine mammary gland function in this review, with particular emphasis on macronutrient transfer and synthesis mechanisms, which might offer a possible approach for regulation of milk synthesis in the future.
| S-EPMC6196465 | biostudies-literature
Project description:Mammary glands are comprised of ducts and terminal lobules that form tree-like structures. Luminal epithelial cells in these lobules undergo differentiation into alveolar cells in pregnancy to support milk production. This study reveals that Scribble (SCRIB), a scaffold protein expressed in progesterone receptor (PGR)-positive cells, plays a critical role in mammary gland alveologenesis in mice. We conditionally deleted Scrib using a Pgr-Cre driver. PGR is heterogeneously expressed throughout the luminal epithelium. Scrib loss in mammary glands by Pgr-Cre (Scribf/fPgrCre/+) shows inefficient alveologenesis and terminal end bud (TEB)-like morphology during pregnancy, resulting in poor milk production and subsequent death of pups after delivery. The differentiation of PGR-positive epithelial cells into Elf5-expressing alveolar cells is defective in Scribf/fPgrCre/+ mice. These changes are reflected in reduced activation of JAK2 and PAK1, resulting in downregulation of pSTAT5, a critical transcriptional factor for alveologenesis. These results provide evidence that SCRIB impacts PGR-positive cell lineage during alveologenesis, which impacts milk production and the health of offspring.
| S-EPMC7241298 | biostudies-literature
Project description:Clinical reports of Zika Virus (ZIKV) RNA detection in breast milk have been described, but evidence conflicts as to whether this RNA represents infectious virus. We infected post-parturient AG129 murine dams deficient in type I and II interferon receptors with ZIKV. ZIKV RNA was detected in pup stomach milk clots (SMC) as early as 1 day post maternal infection (dpi) and persisted as late as 7 dpi. In mammary tissues, ZIKV replication was demonstrated by immunohistochemistry in multiple cell types including cells morphologically consistent with myoepithelial cells. No mastitis was seen histopathologically. In the SMC and tissues of the nursing pups, no infectious virus was detected via focus forming assay. However, serial passages of fresh milk supernatant yielded infectious virus, and immunohistochemistry showed ZIKV replication protein associated with degraded cells in SMC. These results suggest that breast milk may contain infectious ZIKV. However, breast milk transmission (BMT) does not occur in this mouse strain that is highly sensitive to ZIKV infection. These results suggest a low risk for breast milk transmission of ZIKV, and provide a platform for investigating ZIKV entry into milk and mechanisms which may prevent or permit BMT.
| S-EPMC6386411 | biostudies-literature
Project description:BackgroundMicroRNAs (miRNAs) are small non-coding RNAs that have been found to play important roles in silencing target genes and that are involved in the regulation of various normal cellular processes. Until now their implication in the mammary gland biology was suggested by few studies mainly focusing on pathological situations allowing the characterization of miRNAs as markers of breast cancer tumour classes. If in the normal mammary gland, the expression of known miRNAs has been studied in human and mice but the full repertoire of miRNAs expressed in this tissue is not yet available.ResultsTo extend the repertoire of mouse mammary gland expressed miRNAs, we have constructed several libraries of small miRNAs allowing the cloning of 455 sequences. After bioinformatics' analysis, 3 known miRNA (present in miRbase) and 33 new miRNAs were identified. Expression of 24 out of the 33 has been confirmed by RT-PCR. Expression of none of them was found to be mammary specific, despite a tissue-restricted distribution of some of them. No correlation could be established between their expression pattern and evolutionary conservation. Six of them appear to be mouse specific. In several cases, multiple potential precursors of miRNA were present in the genome and we have developed a strategy to determine which of them was able to mature the miRNA.ConclusionThe cloning approach has allowed improving the repertoire of miRNAs in the mammary gland, an evolutionary recent organ. This tissue is a good candidate to find tissue-specific miRNAs and to detect miRNA specific to mammals. We provide evidence for 24 new miRNA. If none of them is mammary gland specific, a few of them are not ubiquitously expressed. For the first time 6 mouse specific miRNA have been identified.
| S-EPMC2683868 | biostudies-literature