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Abundantly present miRNAs in milk-derived extracellular vesicles are conserved between mammals

ABSTRACT: Mammalian milk is not only a source of nutrition for the newborn, but also contains various components that regulate further development. For instance, milk is an abundant source of microRNAs (miRNAs), which are evolutionary conserved small non-coding RNAs that are involved in post-transcriptional regulation of target mRNA. MiRNAs present in milk can occur in extracellular vesicles (EV), which are nanosized membrane vesicles released by many cell types as a means of intercellular communication. The membrane of EV protects enclosed miRNAs from degradation and harbors molecules that allow specific targeting to recipient cells. Although several studies have investigated the miRNA content in milk EV from individual species, little is known about the evolutionary conserved nature of EV-associated miRNAs among different species. In this study, we profiled the miRNA content of purified EV from human and porcine milk. These data were compared to published studies on EV from human, cow, porcine and panda milk to assess the overlap in the top 20 most abundant miRNAs. Interestingly, several abundant miRNAs were shared between species (e.g. let-7 family members let-7a, let-7b, let-7f, and miR-148a). Moreover, these miRNAs have been implicated in immune-related functions and regulation of cell growth and signal transduction. The conservation of these miRNA among species, not only in their sequence homology , but also in their incorporation in milk EV of several species, suggests that they are evolutionarily selected to regulate cell function in the newborn.

ORGANISM(S): Homo sapiens Sus scrofa

PROVIDER: GSE118409 | GEO | 2018/08/11

REPOSITORIES: GEO

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Project description:Background: Maternal pre-pregnancy BMI is a critical factor influencing the composition of breast milk. Breast milk has abundant extracellular vesicles (EVs) containing various biological molecules (cargo), including miRNAs. EVs are not degraded in the gastrointestinal system and circulation; thus, breast milk EVs (bEVs) interact with other organs in breastfed infants and modify the gene expression of recipient cells using miRNAs. In maternal obesity, miRNAs in bEVs are deregulated, which might be associated with adverse health outcomes in infants. In this study, we examined 798 miRNAs to determine which miRNAs are altered in the bEVs of obese mothers and their potential impact on breastfed infants. Methods: We recruited healthy nursing mothers who were either obese (BMI≥30) or lean (BMI<25) based on their pre-pregnancy BMI, and delivered a singleton baby in the prior six months. EVs were isolated from breast milk with ultracentrifugation. bEV characteristics were examined by flow cytometry and fluorescence imaging of EV markers. A total of 798 miRNAs were screened using a NanoString human miRNA panel to find deregulated miRNAs in bEVs of obese mothers compared to lean mothers. Results: We included 65 nursing mothers: 47 lean and 18 obese mothers based on pre-pregnancy BMI. After bEV isolation, we confirmed the expression of general EV markers. Out of 37 EV markers, CD326 was the most highly expressed marker in bEVs. From miRNA analysis using NanoString, we found that the most abundant miRNAs include miR-30b-5p, miR-494-3p, and let-7 families, and the list of top 10 miRNAs was not different between lean and obese mothers. Target genes of the top 10 miRNAs were associated with the EGFR, ErbB, and FoxO signaling pathway. Nineteen miRNAs were deregulated in bEVs of obese mothers (adjusted p < 0.05 cut-off), including miR-575, miR-548g-3p, miR-582-3p, and miR-652-5p. The target genes of these miRNAs are associated with lipid metabolism, inflammatory diseases, and nervous/cardiovascular system development. Conclusion: In this study, we demonstrated altered miRNAs in bEVs of obese mothers and identified the pathways of their potential target genes. Our findings will provide insight for future studies investigating the role of bEVs in breastfed infants.

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Abundantly present miRNAs in milk-derived extracellular vesicles are conserved between mammals

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