Nutrigenomic analyses reveal miRNAs and mRNAs affected by feed restriction in the mammary gland of midlactation dairy cows

PLoS One. 2021 Apr 15;16(4):e0248680. doi: 10.1371/journal.pone.0248680. eCollection 2021.


The objective of this study was to investigate the effects of feed restriction on mammary miRNAs and coding gene expression in midlactation cows. Five Holstein cows and 6 Montbéliarde cows underwent 6 days of feed restriction, during which feed allowance was reduced to meet 50% of their net energy for lactation requirements. Mammary biopsies were performed before and at the end of the restriction period. Mammary miRNA and mRNA analyses were performed using high-throughput sequencing and microarray analyses, respectively. Feed restriction induced a negative energy balance and decreased milk production and fat and protein yields in both breeds. Feed restriction modified the expression of 27 miRNAs and 374 mRNAs in mammary glands from Holstein cows, whereas no significant miRNA change was observed in Montbéliarde cows. Among the 27 differentially expressed miRNAs, 8 miRNAs were associated with dairy QTL. Analysis of target genes indicate that the 8 most abundantly expressed miRNAs control transcripts related to lipid metabolism, mammary remodeling and stress response. A comparison between the mRNAs targeted by the 8 most strongly expressed miRNAs and 374 differentially expressed mRNAs identified 59 mRNAs in common. The bioinformatic analyses of these 59 mRNAs revealed their implication in lipid metabolism and endothelial cell proliferation. These effects of feed restriction on mammary miRNAs and mRNAs observed in Holstein cows suggest a potential role of miRNAs in mammary structure and lipid biosynthesis that could explain changes in milk production and composition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Feed / analysis*
  • Animals
  • Cattle
  • Cell Proliferation / genetics
  • Energy Metabolism
  • Female
  • Food Deprivation / physiology*
  • Gene Expression
  • High-Throughput Nucleotide Sequencing
  • Lactation / genetics*
  • Lipid Metabolism / physiology
  • Lipogenesis
  • Mammary Glands, Animal / metabolism
  • MicroRNAs / genetics
  • Nutrigenomics
  • RNA, Messenger / genetics
  • Transcriptome / drug effects
  • Transcriptome / genetics


  • MicroRNAs
  • RNA, Messenger

Grant support

We thank the Région Auvergne S3 and FEDER for the funding of P-A Billa’s thesis grants (project nr. 23000794/1130 entitled "Innovative biomarkers for the quality products of tomorrow's cattle farming ") awarded to PAB, and ApisGene for the funding of Céline Bourdon’s thesis grants. This research was funded by GISA meta-program of INRAE (Ruminflame and Longhealth projects).