Abstract
Milk is rich in miRNAs that appear to play important roles in the postnatal development of all mammals. Currently, two competing hypotheses exist: the functional hypothesis, which proposes that milk miRNAs are transferred to the offspring and exert physiological regulatory functions, and the nutritional hypothesis, which suggests that these molecules do not reach the systemic circulation of the milk recipient, but merely provide nutrition without conferring active regulatory signals to the offspring. The functional hypothesis is based on indirect evidence and requires further investigation. The nutritional hypothesis is primarily based on three mouse models, which are inherently problematic: 1) miRNA-375 KO mice, 2) miRNA-200c/141 KO mice, and 3) transgenic mice presenting high levels of miRNA-30b in milk. This article presents circumstantial evidence that these mouse models may all be inappropriate to study the physiological traffic of milk miRNAs to the newborn mammal, and calls for new studies using more relevant mouse models or human milk to address the fate and role of milk miRNAs in the offspring and the adult consumer of cow’s milk.
Highlights
Milk contains a plethora of miRNAs, molecules that are known to play pivotal roles in the post-transcriptional regulation of gene expression in various organisms [1, 2]
Milk miRNAs are present in free form within the liquid part of milk, but they are packaged inside carrier vehicles, which include milk exosomes, milk cells as well as other microvesicles such as the milk fat globules [6]
Milk of humans and livestock animals is enriched with immune-related miRNAs [36, 38], which may shape the intestinal immune system [39], but may support the development of thymus-controlled immune regulation [40], both via microvesicle-associated miRNAs and miRNAs contained within milk cells, which have recently been shown to be actively transferred to the thymus of suckling mouse pups (Alsaweed M et al 2016, personal communication)
Summary
Milk contains a plethora of miRNAs, molecules that are known to play pivotal roles in the post-transcriptional regulation of gene expression in various organisms [1, 2]. As has been previously discussed [6], neither of the examined miRNAs (miR-375 and miR-200c) in the study of Title et al [19] was highly expressed in the wild-type mother’s milk of this murine model, whilst both of these miRNAs are known to be involved in the control of endocytosis and/ or exocytosis and to modulate epithelial function, which may influence exosome endocytosis and their uptake. Milk of humans and livestock animals is enriched with immune-related miRNAs [36, 38], which may shape the intestinal immune system [39], but may support the development of thymus-controlled immune regulation [40], both via microvesicle-associated miRNAs and miRNAs contained within milk cells, which have recently been shown to be actively transferred to the thymus of suckling mouse pups (Alsaweed M et al 2016, personal communication)
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