Circulating miRNA signatures of early pregnancy in cattle

Ioannidis, Jason; Donadeu, F.X.

doi:10.1186/s12864-016-2529-1

Cited by 84 publications

(94 citation statements)

References 52 publications

(47 reference statements)

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“…Our novel results using small RNA sequencing and RT-qPCR profiling show wide changes in circulating miRNA profiles occurring by Day 60 of pregnancy in cattle, in contrast with the much smaller differences previously reported from high-throughput analysis of small RNAs earlier during pregnancy (Days 16 and 24) [23]. Specifically, we identify a subset of miRNAs (let-7f, let-7c, miR-30c, miR-101, miR-26a, miR-205 and miR-143), the levels of which increase distinctly in circulation (up to 6-fold) in Day 60 pregnant relative to non-pregnant (Day 0) cows, and which provide novel molecular candidates involved in the establishment of pregnancy in cattle.…”

Section: Discussionmentioning

confidence: 53%

“…The 15 most abundant miRNAs in bovine plasma are listed in Table 2. Eleven of these miRNAs were also among the most abundant in our previous cattle study [23]. …”

Section: Resultsmentioning

confidence: 94%

“…Eleven Holstein-Friesian heifers, 14–17 months old, that had never been inseminated, were oestrus-synchronised and artificially inseminated at oestrus following previously described procedures [23]. Pregnancy was confirmed by trans-rectal ultrasound on Days 35 and 60 post-insemination.…”

Section: Methodsmentioning

confidence: 99%

“…Pregnancy was confirmed by trans-rectal ultrasound on Days 35 and 60 post-insemination. Plasma samples were collected from the jugular vein in EDTA tubes (Becton Dickinson, USA) on Days 0, 8, 16 and 60 after insemination, as described before [23, 25]. The ratio between miR-451 and miR-23a was used as an indicator of haemolysis [26]; most samples had a miR ratio < 5, indicating absence of haemolysis (S1 Fig).…”

Section: Methodsmentioning

confidence: 99%

“…We recently reported for the first time changes in circulating miRNA levels during early pregnancy (Days 16 and 24) in cattle [23]. Perhaps not surprisingly, differences in miRNA levels at such early stage of pregnancy were in general very small, which, considering intrinsic biases associated with RNA sequencing [24], may have prevented the wide identification of robust miRNA biomarkers.…”

Section: Introductionmentioning

confidence: 99%

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

Ioannidis

Donadeu

2017

PLoS ONE

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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.

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Section: Discussionmentioning

confidence: 53%

“…The 15 most abundant miRNAs in bovine plasma are listed in Table 2. Eleven of these miRNAs were also among the most abundant in our previous cattle study [23]. …”

Section: Resultsmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Ioannidis

Donadeu

2017

PLoS ONE

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Exosomes from bovine endometrial epithelial cells ensure trophoblast cell development by miR‐218 targeting secreted frizzled related protein 2

Wang

Xie

et al. 2020

Journal Cellular Physiology

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Endometritis is a common disease affecting fertility in cows during the perinatal period, which disturbs the molecular milieu of the uterine environment and impairs embryo development and implantation. Exosomes are important extracellular components that transmit a variety of micro RNAs (miRNAs), which perform key regulatory functions. In this study, we investigated plasma exosomal miRNAs from cows with endometritis and from cultured endometrial epithelial cells (EECs) challenged with lipopolysaccharide (LPS) to explore the role of EEC-derived exosomes and their miRNAs in bovine endometritis. Plasma exosomes were collected from nine healthy dairy cows and nine dairy cows with endometritis, and culture supernatant exosomes were isolated from EECs challenged with or without LPS. Exosomal RNA was extracted using commercial kits and miRNA profiles were generated using RNA-seq. We found that miR-218 was differentially expressed in EECs under conditions of endometrial inflammation. Inhibition studies suggested that reduced levels of miR-218 in EEC-derived exosomes when transferred into placental trophoblast cells impaired embryonic development and decreased placental trophoblast cell migration by targeting secreted frizzled related protein 2. We propose that exosomal miR-218 secreted from EECs acts as a driver of embryonic development and differentiation. In addition, exosomal miR-218 may provide a valuable diagnostic marker for bovine endometritis.

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Circulating microRNA as candidates for early embryonic viability in cattle

Pohler¹,

Green

Moley

et al. 2017

Molecular Reproduction Devel

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Blood-borne extracellular vesicles (i.e. exosomes and microvesicles) carrying microRNAs (miRNAs) could make excellent biomarkers of disease and different physiologic states, including pregnancy status. We tested the hypothesis that circulating extracellular vesicle-derived miRNAs might differentiate the pregnancy status of cows that had maintained pregnancy to Day 30 from non-pregnant cows or from those that exhibited embryonic mortality between Days 17–30 of gestation. Cows were randomly assigned for artificial insemination with fertile semen (n= 36) or dead semen (n=8; control group) on Day 0 (day of estrus). Blood was collected from all animals on Day 0 and on Days 17 and 24 after artificial insemination. Cows receiving live sperm were retrospectively classified as pregnant on Day 30 (n=17) or exhibiting embryonic mortality between Days 17–30 (n=19). Extracellular vesicles from Day-17 and -24 samples were isolated from serum using ultra-centrifugation, and their presence was confirmed by nanoparticle tracking and Western blot analyses (for CD81) prior to RNA extraction. MicroRNA sequencing was performed on pregnant, embryonic-mortality, and control cows (n=4 per day), for a total of 24 independent reactions. In total, 214 miRNAs were identified in serum, 40 of which were novel. Based on differential abundance parameters, we identified 32 differentially abundant loci, representing 27 differentially abundant mature miRNA. At Days 17 and 24, specific miRNAs (e.g. miR-25, -16b and -3596) were identified that differentiated the pregnancy status. In summary, we identified several circulating extracellular vesicles derived miRNAs that differ in abundance between embryonic mortality and pregnant cows.

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Circulating miRNA signatures of early pregnancy in cattle

Cited by 84 publications

References 52 publications

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

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

Exosomes from bovine endometrial epithelial cells ensure trophoblast cell development by miR‐218 targeting secreted frizzled related protein 2

Circulating microRNA as candidates for early embryonic viability in cattle

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