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Analyzing the Function of Exosome’s microRNA in Milk by Comparing the Expression of microRNA in Milk and Exosome

ABSTRACT: Milk contains fats, carbohydrates, proteins, RNAs and enzymes, but also mRNA and microRNAs(miRNA), which plays an important role in neonatal innate and adaptive immunity. The following study investigates whether or not miRNA of exosome in milk is a vital pathway for miRNA of milk absorbing. Briefly, 280 pre-miRNAs and 326 mature miRNA were found. 37 exosomal miRNAs were upregulated (twice fold) compared to miRNAs found outside the exosomes. Among these miRNAs, ssc-miR-193a-3p’s expression was up regulated 1467.35 times, while ssc-miR-423-5p、ssc-miR-551a、ssc-miR-138、ssc-miR-1 and ssc-miR-124a were highly concentrated and upregulated from 13.58 to 30.06 times. Moreover, all of these miRNAs play essential roles in cell’s development and basic physiology processes in immune system. Following the analysis of target gene prediction and related signaling pathways, 9262 target genes showed to be mainly concentrated on three signaling pathway: metabolic pathways、pathways in cancer, and Phosphatidylinositol 3-kinase /Protein Kinase B(PI3K/Akt) signaling pathways. In addition, more than 20 miRNAs showed to be highly concentrated on exosomes, such as MECP2、GYS1、 LRRC8A、BCL9L、PHRF1 and ELOVL1, all closely related to immunity and engendering of gene. After performing in-depth research on miRNA’s localization, distribution and function related metabolism, we found that these exosome concentrated miRNA’s target genes were interrelated to development and basic cell functions, like metabolism and immunity. These results imply that miRNAs in breast milk can influence offspring via milk exosomes.

ORGANISM(S): Sus scrofa

PROVIDER: GSE107652 | GEO | 2017/12/05

SECONDARY ACCESSION(S): PRJNA420976

REPOSITORIES: GEO

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Project description:Feed restriction during the early life of ewe lambs (F0) triggers the transfer of epigenetic marks to the next generation, thus impairing the reproductive performance of F1. However, the effects of this factor on milk production and composition, including its abundance in regulatory miRNA (many of which are contained in exosomes, small vesicles of endocytic origin that play a role in the modulation of immune response of the offspring), has not been tested so far. Therefore, in this study, the replacement ewe lambs (F0) obtained in a previous project (a group of ewes fed milk replacer ad libitum –ADL– vs. a group of ewes restricted –RES– to 62.5% the intake level of milk replacer during the suckling period) were raised under similar post-weaning conditions and mated to obtain the progeny (F1). The F1 dairy ewes were also mated, and six of these F1 dairy ewes were selected and divided into two groups: the F1-ADL group (n=3) born from F0-ADL and the F1-RES group (n=3), born from F0-RES animals. Milk production was controlled during the peak lactation period, and milk samples were obtained for each gland separately to measure chemical composition, somatic cell counts, and bacteriology. Exosomes were also isolated for each gland separately to define the miRNA content. The miRNAome was determined following a Next Generation Sequencing approach. The first preliminary results indicate significant differences in the abundance of five miRNAs in the milk obtained during the peak of lactation. Thus, oar-miR-150, oar-miR-221, oar-miR-23a, oar-miR-27a, oar-miR-376c were all down modulated in F1-RES when compared to F0-ADL. Most of these miRNAs have been found to play a role in biological functions such as development, apoptosis, muscle differentiation, reproduction, or milk production. Moreover, somatic cell count (SCC) was reduced significantly in milk samples during the peak of lactation of F1-RES dairy sheep. No significant differences were found in milk production, the chemical composition of milk (fat, protein, lactase), or bacteriology (colony forming units, CFU). This study's results provide some evidence of the effects of nutritional programming events on the milk's bioactive components.

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Analyzing the Function of Exosome’s microRNA in Milk by Comparing the Expression of microRNA in Milk and Exosome

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