Changes in circulating microRNA levels can be identified as early as day 8 of pregnancy in cattle

PLoS One. 2017 Apr 5;12(4):e0174892. doi: 10.1371/journal.pone.0174892. eCollection 2017.

Abstract

Poor reproductive performance remains a major issue in the dairy industry, with low conception rates having a significant impact on milk production through extended calving intervals. A major limiting factor is the lack of reliable methods for early pregnancy diagnosis. Identification of animals within a herd that fail to conceive within 3 weeks after insemination would allow early re-insemination and shorten calving intervals. In a previous study, we found an increase in plasma miR-26a levels in Day 16-pregnant relative to non-pregnant heifers, however changes in miRNA levels that early during pregnancy were very small which likely prevented the identification of robust biomarkers. In this study, we extended our analyses to a wider interval during pregnancy (Days 8 to 60, n = 11 heifers) with the rationale that this may facilitate the identification of additional early pregnancy miRNA biomarkers. Using small RNA sequencing we identified a total of 77 miRNAs that were differentially expressed on Day 60 relative to Day 0 of pregnancy. We selected 14 miRNAs for validation by RT-qPCR and confirmed significant differences in the expression of let-7f, let-7c, miR-30c, miR-101, miR-26a, miR-205 and miR-143 between Days 0 and 60. RT-qPCR profiling throughout Days 0, 8, 16 and 60 of pregnancy showed a distinct increase in circulating levels of miR-26a (3.1-fold, P = 0.046) as early as Day 8 of pregnancy. In summary, in contrast to earlier stages of pregnancy (≤ Day 24), marked differences in the levels of multiple miRNAs can be detected in circulation by Day 60 in cattle. Retrospective analyses showed miR-26a levels to be increased in circulation as early as Day 8, sooner than previously reported in any species, suggesting a biological role for this miRNA in the very early events of pregnancy.

MeSH terms

  • Animals
  • Cattle / blood*
  • Cattle / genetics
  • Female
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Polymerase Chain Reaction / veterinary
  • Pregnancy
  • Pregnancy Tests / veterinary
  • Pregnancy, Animal / blood*

Substances

  • MicroRNAs

Grants and funding

This work was supported BBSRC, grant BB/K501578/1 to FXD (http://www.bbsrc.ac.uk/) and Zoetis Inc (https://www.zoetis.com) to FXD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.