Breast Milk Extracellular Vesicle miRNAs from a Population-Based Cohort in the Faroe Islands
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE146880 | GEO | 2021/03/12
REPOSITORIES: GEO
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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 (HM) is rich in miRNAs, which are thought to contribute to infant protection and development. We used deep sequencing to profile miRNAs in the cell and lipid fractions of HM obtained post-feeding from 10 lactating women in month 2, 4, and 6 postpartum. In both HM fractions, 1,195 mature known miRNAs were identified, which were positively associated with the cell (p=0.048) and lipid (p=0.010) content of HM. An additional 5,167 novel miRNA species were predicted, of which 235 were high-confidence miRNAs expressed in ≥3 samples with total reads of >20. HM cells contained more known miRNAs than HM lipids (1,136 and 835 respectively, p<0.001), with 146 of the common species upregulated in HM cells and 133 in HM lipids (p<0.05). Further, the profile of the novel miRNAs was very different between the two HM fractions, with the majority conserved in the cell fraction and being mother-specific. However, out of the 776 known miRNA species commonly present in the two HM fractions, 63.9% were similarly expressed (p>0.05), with great similarities in the profile of top 20 known miRNAs. These were largely similar also between the three lactation stages examined, as were the total miRNA concentration, and the number and overall expression of the known miRNAs commonly present in the two HM fractions (p>0.05). Yet, approximately a third of known miRNAs were differentially expressed during the first 6 months of lactation (p<0.05), with more pronounced miRNA upregulation seen in month 4. These findings indicate that although the total miRNA concentration of HM cells and lipids provided to the infant does not change in the first 6 months of lactation, the miRNA composition is somewhat altered, particularly in month 4 compared to months 2 and 6. This may reflect the remodeling of the gland in response to infant feeding patterns, which usually change after exclusive breastfeeding, and thus adaptation to infant needs.
2016-04-25 | GSE75726 | GEO
Project description:The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations. We assessed the impact of prenatal exposure to arsenic on genome-wide miRNA expression profiles and their potential influence on gene expression patterns in the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort. This cohort includes residents from Gómez Palacio, located in the state of Durango in the Lagunera region of Northern Mexico. A total of 200 pregnant women residing in Gómez Palacio, State of Durango, Mexico, were recruited at the General Hospital of Gómez Palacio to participate in the BEAR prospective pregnancy cohort. The present study focuses on miRNA expression profiles and utilizes 40 samples obtained from mother-newborn pairs selected from the larger cohort (n=200). The subcohort was selected to include subjects exposed to varying levels of arsenic as determined by both total arsenic in maternal urine (U-tAs) and inorganic arsenic in drinking water (DW-iAs). Cord blood samples were collected from the newborns immediately after infant delivery. Blood samples were collected using PreAnalytix PaxGene RNA tubes and extracted using the PAXgene RNA Kit, per standard protocol (Qiagen, Valencia, CA). Isolated RNA used for microarray analysis were amplified and labeled using the NuGEN Ovation Pico WTA System V2 and Encore Biotin Module, respectively (NuGEN, San Carlos, CA). RNA isolated from 40 cord blood samples were labeled and hybridized to the Agilent Human miRNA Microarray, based off miRBase v16.0.
2014-01-22 | E-GEOD-48353 | biostudies-arrayexpress
Project description:Very little is known about miRNAs found in breastmilk cells, which also reflect the cells of the lactating mammary epithelium. Our hypothesis is that breastmilk cells are richer in miRNA compared to other milk fractions, such as skim milk. Further, the effects of milk removal by the infant on milk cell miRNA content and/or composition have not been investigated. Breastmilk cells conserved higher miRNA content than previously published lipid and skim fractions of breastmilk as well as other known sources of miRNA in humans. Specifically, 1,467 known mature miRNAs were identified and a further 1996 novel miRNAs, of which 89 were highly expressed. As previously shown, post-feed milk contained more cells than pre-feed milk, and the same was observed for miRNA content. However, no statistically significant difference was found in the expression of the total known and novel miRNAs between pre- and post-feed milk (p=0.76), although 27 known miRNAs and 1 novel miRNA were higher expressed in post-feed milk. As expected, samples richer in viable cells contained more known miRNAs (p = 0.01). Functional analysis of the top 10 most highly expressed known miRNAs showed that they may be potentially involved in crucial roles for the infant, including body fluid balance, thirst, appetite, immune responses, and development. In conclusion, breastmilk is highly rich in miRNA which may play important functions in the breastfed infant and the lactating breast. Milk removal by the infant can influence the total miRNA content of breastmilk, similar to its cell and fat content, but the miRNA composition remains constant
2016-10-04 | GSE71098 | GEO
Project description:Influenza virus transmission between mothers and nursing-infants has not been investigated although mothers and infants often develop severe disease. Ferrets are considered the most appropriate model for influenza studies. We investigated influenza transmission in infant and nursing-mother ferrets. Influenza infected infants transmitted virus to mother mammary glands leading to live virus excretion in milk and influenza virus positive mammary gland epithelial cells. Global gene expression analysis showed down-regulation of milk production and induction of breast involution and oncogenesis pathways. Our results provide insight into influenza transmission between mothers and infants which may impact fields of infectious disease, maternal/infant health and neoplasm etiology. Total RNA was obtained from nursing mother ferret mammary glands at days 3/4 and 6/7 post-intranasal kit infection with 10^5 EID50 A/California/07/2009 (H1N1). Total RNA was also collected from uninfected control nursing mother mammary gland tissues (n = 3). Changes in gene expression relative to uninfected tissue controls were then investigated.
2015-09-10 | E-GEOD-63082 | biostudies-arrayexpress
Project description:The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations. We assessed the impact of prenatal exposure to arsenic on genome-wide miRNA expression profiles and their potential influence on gene expression patterns in the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort. This cohort includes residents from Gómez Palacio, located in the state of Durango in the Lagunera region of Northern Mexico. A total of 200 pregnant women residing in Gómez Palacio, State of Durango, Mexico, were recruited at the General Hospital of Gómez Palacio to participate in the BEAR prospective pregnancy cohort. The present study focuses on gene expression profiles and utilizes 38 samples obtained from mother-newborn pairs selected from the larger cohort (n=200). The subcohort was selected to include subjects exposed to varying levels of arsenic as determined by both total arsenic in maternal urine (U-tAs) and inorganic arsenic in drinking water (DW-iAs). Cord blood samples were collected from the newborns immediately after infant delivery. Blood samples were collected using PreAnalytix PaxGene RNA tubes and extracted using the PAXgene RNA Kit, per standard protocol (Qiagen, Valencia, CA). Isolated RNA used for microarray analysis were amplified and labeled using the NuGEN Ovation Pico WTA System V2 and Encore Biotin Module, respectively (NuGEN, San Carlos, CA). RNA isolated from 38 cord blood samples were labeled and hybridized to the Affymetrix Human Gene 2.0 ST Array.
2014-01-22 | E-GEOD-48354 | biostudies-arrayexpress
Project description:Influenza virus transmission between mothers and nursing-infants has not been investigated although mothers and infants often develop severe disease. Ferrets are considered the most appropriate model for influenza studies. We investigated influenza transmission in infant and nursing-mother ferrets. Influenza infected infants transmitted virus to mother mammary glands leading to live virus excretion in milk and influenza virus positive mammary gland epithelial cells. Global gene expression analysis showed down-regulation of milk production and induction of breast involution and oncogenesis pathways. Our results provide insight into influenza transmission between mothers and infants which may impact fields of infectious disease, maternal/infant health and neoplasm etiology.
2015-09-10 | GSE63083 | GEO
Project description:Influenza virus transmission between mothers and nursing-infants has not been investigated although mothers and infants often develop severe disease. Ferrets are considered the most appropriate model for influenza studies. We investigated influenza transmission in infant and nursing-mother ferrets. Influenza infected infants transmitted virus to mother mammary glands leading to live virus excretion in milk and influenza virus positive mammary gland epithelial cells. Global gene expression analysis showed down-regulation of milk production and induction of breast involution and oncogenesis pathways. Our results provide insight into influenza transmission between mothers and infants which may impact fields of infectious disease, maternal/infant health and neoplasm etiology.
2015-09-10 | GSE63082 | GEO
Project description:Milk is an indispensable source of infant nutrition in all mammals, made up of complex constituents needed for infant nourishment and immunity. Comparison of miRNA profiles between infected and non-infected/control Holstein cattle could provide important information on the differences in composition of milk at the level of miRNA, if any, and broaden our perspective and understanding of the effect of pathology on cellular compositions and functions. In the present study we therefore analyzed the expression profiles of bovine milk exosomal miRNAs during S. uberis infection and identified 328 known miRNAs and 82 high-confidence miRNA candidates by deep sequencing. The top 10 miRNAs in both control and infected replicates accounted for approximately 80% of total counts, which were predicted to target 605 genes using two computational approaches. In addition, 15 significantly differentially expressed miRNAs were identified between control and infected replicates during S. uberis infection, and a total of 1,852 unique genes were predicted to be targeted by these miRNAs. Ingenuity Canonical Pathways and Diseases and Biological Function analyses using IPA indicated that the identified miRNAs targets mainly enriched in regulating the innate and adaptive immune responses in newborns, as well as infant growth and development. The characterization of these miRNAs could contribute to a better understanding of the molecular mechanisms involved in lactation physiology and milk imparted immune function in the dairy cattle.
2017-07-25 | GSE59794 | GEO
Project description:Analysis of genome-wide hydroxymethylation within infant placental tissue collected at term. These samples have been collected from the RhodeIsland Child Health Study (RICHS) cohort.
2016-07-01 | GSE71719 | GEO