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INRA
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31326 Castanet Tolosan CEDEX - France

Dernière mise à jour : Mai 2018

Menu Logo Principal AgroParisTech Université Paris-Saclay

INRA GABI Unit

GABI : Génétique Animale et Biologie IntégrativeUnité Mixte de Recherche INRA - AgroParisTech

Nutriregulation of microRNA in the mammary gland of ruminants

Nutriregulation of microRNA in the mammary gland of ruminants
© INRA
microRNA are small RNA that are implicated in many biological processes. Establishing a catalogue of them in the mammary gland was a prerequisite for the study of nutritional regulation of their expression. A caprine model under extreme nutrition conditions and a model for lipid supplementation in the dairy cow respectively allowed identifying 30 and 2 nutriregulated microRNA.

Context and Stakes

Diet affects milk composition which determines to a large extent, its nutritional quality. In the mammary gland, synthesis and secretion of milk constituents implicate numerous genes whose expression is modulated by the diet, however, little information is available on the underlying regulation mechanisms. microRNA (miRNA) are small non-coding RNA (18-25 nucleotides) that are associated with RNAm for the regulation of expression. They are implicated in the regulation of many different biological processes. Thus, recent studies describing the role of miRNA in lactation or the development of the mammary gland1 have led to new investigations on the understanding of the mechanisms implicated. Thus, the objective of our studies is to establish a map of the miRNA present in the mammary gland of ruminants and to evaluate nutritional regulation. 

Results: the first step consisted in gaining knowledge on the miRNA that are expressed in the mammary gland by establishing a reference miRNome using high-throughput sequencing in mice, cattle and goats2,3. These data are available to the scientific community and may serve as a reference for all future studies. The establishment of the caprine mammary gland miRNome obtained using an "extreme" (fed  vs food-deprived for 48h) revealed 30 miRNA that are differentially expressed in the mammary gland of goats in lactation4. A bovine model closer to farming conditions allowed the identification of two nutriregulation miRNA upon sunflower oil supplementation in a diet rich in concentrates. The in silico analysis of targeted RNAm of the nutriregulated miRNA showed their potential role in the metabolism of lipids. In addition, differential expression of specific targets were previously described in these models5, such as Esr1 or Elovl6 which are genes that are essential for lactation. These studies therefore provide the first elements necessary for the understanding of gene expression regulation in response to diet and the role of miRNA in lactation in ruminants.

Perspectives

In order to gain more precise information on miRNA function, functional studies have begun in vitro and must be pursued. In addition, experimental data (RNA and miRNA) are the bases for data integration methods of "omics" of different origins. Similarly, a partnership has allowed the initiation of a study using miRNome sequencing and annotation data in caprine mapping to identify their Single Nucleotide Polymporphis (SNP) in relation with the location of quantitative traits (QTL) in milk. Finally, caprine and bovine mammary miRNomes will be references for the identification of the miRNA present in milk. The presence of miRNA in milk will lead to new areas of investigation both for their use as biomarkers (metabolic, physiological, health status) and  for their potential effects on consumers (passage through the gastro-intestinal barrier, health effects in the newborn, ...).

Valorization

Articles 2, 3 and 4 indicated below and the doctoral dissertation of Lenha Mobuchon December 2015.

References 

1- Le Guillou S., Sdassi N., Laubier J., Passet B., Vilotte M., Castille J., Laloë D., Polyte J., Bouet S., Jaffrézic F., Cribiu E.-P., Vilotte J.-L., Le Provost F. Overexpression of miR-30b in the developing mouse mammary gland causes a lactation defect and delays involution. PloS One 2012, 7: e45727, doi: 10.1371/journal.pone.0045727
2- Le Guillou S, Marthey, S, Laloe D, Laubier J, Mobuchon L, Leroux C and Le Provost F, Characterization and comparison of lactating mouse and bovine mammary gland miRNomes. PLoS ONE 2014; 9(3):e91938. DOI:10.1371/journal.pone.0091938
3- Mobuchon L, Marthey S, Boussaha M, Le Guillou S, Leroux C and Le Provost F. Annotation of the goat genome using Next Generation Sequencing of microRNA expressed by the lactating mammary gland: comparison of three approaches. BMC Genomics 2015; 16(1):285. DOI:10.1186/s12864-015-1471-y
4- Mobuchon L, Marthey S, Le Guillou S, Laloe D, Le Provost F and Leroux C. Food deprivation affects the miRNome in the lactating goat mammary gland. PlosOne, 2015, 10(10):e0140111. doi: 10.1371/journal.pone.0140111.
5- Ollier S, Robert-Granié C, Bernard L, Chillard Y and Leroux C. Mammary transcriptome analysis of food-deprived lactating goats highlights genes involved in milk secretion and programmed cell death. J Nutr. 2007, 137 (3): 560-7.