Proteomic analysis of exosomes derived from human mature milk and colostrum of mothers with term, late preterm, or very preterm delivery

Freiría-Martínez, Luis; Iglesias-Martínez-Almeida, Marta; Rodríguez-Jamardo, Cynthia; Rivera-Baltanás, Tania; Comís-Tuche, María; Rodrígues-Amorím, Daniela; Fernández-Palleiro, Patricia; Blanco-Formoso, María; Álvarez-Chaver, Paula; Diz-Chaves, Yolanda; Gonzalez-Freiria, Natalia; Martín-Forero-Maestre, Montserrat; Fernández-Feijoo, Cristina Durán; Suárez-Albo, María; Fernández-Lorenzo, Jose Ramón; Guisán, Ana Concheiro; Olivares, Jose Manuel; Spuch, Carlos

doi:10.1039/d3ay01114c

Cited by 4 publications

(6 citation statements)

References 80 publications

(129 reference statements)

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“…Freiría‐Martínez et al. also reported proteomics analysis of term and preterm whole HM and EVs (Freiría‐Martínez et al., 2023 ). Between the two groups reporting differentially expressed proteins, both describe upregulation of lysozyme, and Wang et al.…”

Section: Discussionmentioning

confidence: 98%

“…Between the two groups reporting differentially expressed proteins, both describe upregulation of lysozyme, and Wang et al. also report increased levels of LF, in preterm HM EVs (Freiría‐Martínez et al., 2023 ; Wang et al., 2019 ). Although these proteins were present in our dataset, we did not detect significantly different expression levels.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Gestational age at birth influences protein and RNA content in human milk extracellular vesicles

Vahkal,

Altosaar,

Tremblay

et al. 2023

J of Extracellular Bio

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Human milk extracellular vesicles (HM EVs) are proposed to protect against disease development in infants. This protection could in part be facilitated by the bioactive EV cargo of proteins and RNA. Notably, mothers birth infants of different gestational ages with unique needs, wherein the EV cargo of HM may diverge. We collected HM from lactating mothers within two weeks of a term or preterm birth. Following purification of EVs, proteins and mRNA were extracted for proteomics and sequencing analyses, respectively. Over 2000 protein groups were identified, and over 8000 genes were quantified. The total number of proteins and mRNA did not differ significantly between the two conditions, while functional bioinformatics of differentially expressed cargo indicated enrichment in immunoregulatory cargo for preterm HM EVs. In term HM EVs, significantly upregulated cargo was enriched in metabolism‐related functions. Based on gene expression signatures from HM‐contained single cell sequencing data, we proposed that a larger portion of preterm HM EVs are secreted by immune cells, whereas term HM EVs contain more signatures of lactocyte epithelial cells. Proposed differences in EV cargo could indicate variation in mother's milk based on infants’ gestational age and provide basis for further functional characterisation.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Gestational age at birth influences protein and RNA content in human milk extracellular vesicles

Vahkal,

Altosaar,

Tremblay

et al. 2023

J of Extracellular Bio

View full text Add to dashboard Cite

show abstract

“…For example, the RhoA signaling pathway plays a key role in PPD by participating in the process of glutamatergic synaptic stress and the release of AMPA receptors to dendritic spines (Gerges et al, 2004 ; Olivier et al, 2015 ). ANXA5 is a Ca 2+ ‐dependent membrane and phospholipid‐binding protein, and Ca 2+ promotes the synthesis of 5‐HT, thereby playing an important role in preventing the development of PPD (Freiría‐Martínez et al, 2023 ; Robinson et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

“…2+ -dependent membrane and phospholipid-binding protein, and Ca 2+ promotes the synthesis of 5-HT, thereby playing an important role in preventing the development of PPD(Freiría-Martínez et al, 2023;Robinson et al, 2014).Compared with PPD, genes associated with altered brain function in PPD-A are predominantly enriched in biological pathways F I G U R E 7 PPD and PPD-A related neurotransmitter receptors. Spatial Pearson correlation analyses between statistical t maps of SampEn and FCs and neurotransmitter density maps have identified PPD and PPD-A-related neurotransmitter receptors.…”

mentioning

confidence: 99%

Molecular basis underlying default mode network functional abnormalities in postpartum depression with and without anxiety

Chen,

Yang,

et al. 2024

Human Brain Mapping

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Although Postpartum depression (PPD) and PPD with anxiety (PPD‐A) have been well characterized as functional disruptions within or between multiple brain systems, however, how to quantitatively delineate brain functional system irregularity and the molecular basis of functional abnormalities in PPD and PPD‐A remains unclear. Here, brain sample entropy (SampEn), resting‐state functional connectivity (RSFC), transcriptomic and neurotransmitter density data were used to investigate brain functional system irregularity, functional connectivity abnormalities and associated molecular basis for PPD and PPD‐A. PPD‐A exhibited higher SampEn in medial prefrontal cortex (MPFC) and posterior cingulate cortex (PPC) than healthy postnatal women (HPW) and PPD while PPD showed lower SampEn in PPC compared to HPW and PPD‐A. The functional connectivity analysis with MPFC and PPC as seed areas revealed decreased functional couplings between PCC and paracentral lobule and between MPFC and angular gyrus in PPD compared to both PPD‐A and HPW. Moreover, abnormal SampEn and functional connectivity were associated with estrogenic level and clinical symptoms load. Importantly, spatial association analyses between functional changes and transcriptome and neurotransmitter density maps revealed that these functional changes were primarily associated with synaptic signaling, neuron projection, neurotransmitter level regulation, amino acid metabolism, cyclic adenosine monophosphate (cAMP) signaling pathways, and neurotransmitters of 5‐hydroxytryptamine (5‐HT), norepinephrine, glutamate, dopamine and so on. These results reveal abnormal brain entropy and functional connectivities primarily in default mode network (DMN) and link these changes to transcriptome and neurotransmitters to establish the molecular basis for PPD and PPD‐A for the first time. Our findings highlight the important role of DMN in neuropathology of PPD and PPD‐A.

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“…Extracellular vesicles (EVs) include heterogeneous distributions of cell-secreted particles extensively utilized for intercellular communication and metabolite transport. − Due to their innate or engineered compositions, EVs have promise as diagnostic biomarkers and delivery vehicles for therapeutic payloads. − Of significance is that EVs encompass diverse subsets of particles, primarily distinguished by size and origin. Exosomes, for example, have a characteristic diameter, ranging from 30 to 150 nm.…”

Section: Introductionmentioning

confidence: 99%

Delineating Bovine Milk Derived Microvesicles from Exosomes Using Proteomics

Couse,

Cox-Vazquez,

Ghatak

et al. 2024

J. Proteome Res.

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In the work presented herein, a simple serialpelleting purification strategy combined with a mass spectrometrybased proteomics analysis was developed as a means of discerning differences in extracellular vesicle (EV) populations found in bovine milk samples. A sequence of ultracentrifugation speeds was used to generate changes in the abundances of EV populations, allowing for the identification of associated proteins. A metric was developed to determine the relative abundances of proteins in large EVs (>200 nm) and small EVs (<200 nm). Of the 476 proteins consistently found in this study, 340 are associated with vesicular components. Of these, 156 were heavily enriched in large EVs, 155 shared between large and small EVs, and 29 heavily enriched in small EVs. Additionally, out of 68 proteins annotated as exosome proteins, 32 were enriched in large EVs, 27 shared between large and small EVs, 5 enriched in small EVs, and 7 were found to be nonvesicular contaminant proteins. The top correlated proteins in the small EV group were predominantly membrane-bound proteins, whereas the top correlated proteins in the large EV group were mostly cytosolic enzymes for molecular processing. This method provides a means of assessing the origins of vesicle components and provides new potential marker proteins within discrete vesicle populations.

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Proteomic analysis of exosomes derived from human mature milk and colostrum of mothers with term, late preterm, or very preterm delivery

Abstract: The growth and development of the human brain is a long and complex process that requires a precise sequence of genetic and molecular events. This begins in the third week...

Cited by 4 publications

References 80 publications

Gestational age at birth influences protein and RNA content in human milk extracellular vesicles

Gestational age at birth influences protein and RNA content in human milk extracellular vesicles

Molecular basis underlying default mode network functional abnormalities in postpartum depression with and without anxiety

Delineating Bovine Milk Derived Microvesicles from Exosomes Using Proteomics

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