Plasma extracellular vesicle miRNAs as potential biomarkers of superstimulatory response in cattle

Abstract

The ability to predict superstimulatory response would be a beneficial tool in assisted reproduction. Using small RNAseq technology, we profiled extracellular vesicle microRNA (EV-miRNA) abundance in the blood plasma of heifers exhibiting variable responses to superstimulation. Estrous synchronized crossbred beef heifers (n = 25) were superstimulated and blood samples were collected from each heifer on Day 7 of consecutive unstimulated (U) and superstimulated (S) cycles. A subset of high (H) and low (L) responders was selected depending on their response to superstimulation and EV-miRNA profiles were analysed at both time-points in each heifer. Approximately 200 known miRNAs were detected in each sample with 144 commonly detected in all samples. A total of 12 and 14 miRNAs were dysregulated in UH vs. UL and in SH vs. SL heifers, respectively. Interestingly, miR-206 and miR-6517 exhibited the same differential expression pattern in H compared to L heifers both before and after superstimulation. Pathway analysis indicated that circadian rhythm and signaling pathways were among the top pathways enriched with genes targeted by dysregulated miRNAs in H vs. L responding heifers. In conclusion, heifers with divergent ovarian responses exhibited differential expression of plasma EV-miRNAs which may be used as a potential biomarker to predict superstimulation response.

Dynamics of inflammatory cytokine expression in bovine endometrial cells exposed to cow blood plasma small extracellular vesicles (sEV) may reflect high fertility

“…Systemic blood flow is a critical supply channel of cellular signalling mediators specifically through sEV, which activates phenotypic changes throughout the entire organ system of an organism 68 , 69 . Plasma EV cargo facilitates critical functions specifically during reproduction and recent studies have identified EV miRNAs as a potential biomarker to identify super-stimulatory response during artificial insemination (AI) of cattle 70 . Nonetheless, proteomic content of circulating plasma exosomes have been identified to distinguish dairy cows with or without uterine infection 71 .Thus, we believe the selection of plasma sEV reflects an excellent cross-section of the physiology of the dairy cows.…”

Small-extracellular vesicles and their microRNA cargo from porcine follicular fluids: the potential association with oocyte quality

“…Another interesting group of miRNAs including miR-206, miR-133b, and miR-133a-3p showed a significant up-regulation in the LQ compared to the HQ group. The same three miRNAs exhibited a higher expression pattern in the EVs isolated from the blood plasma of low- compared to high-response heifers to ovarian stimulation [ 47 ]. Both miR-206 and miR-133a are highly correlated with E2 deficiency by targeting and reducing the expression of E2 receptor-α, which mediates the biological activity of E2 in ovarian follicular cells and subsequently affects oocyte quality [ 48 – 51 ].…”

Identification of differentially expressed mRNAs and miRNAs in spermatozoa of bulls of varying fertility

“…Notably, three miRNA including bta-miR-655, bta-miR-2285p and bta-miR-2285t were listed as having a target mRNA gene RBBP6 with increased expression in the HF group. While bta-miR-2285p and bra-miR-2285t have been reported to have roles in the bovine estrous cycle ( 61 , 62 ), RBBP6 sperm transcripts were reportedly involved in utero embryonic development ( 63 ). Analysis of the transcripts targeted by the differentially expressed miRNAs showed that five of them (bta-miR-2285p, bta-miR-98, bta-miR-155, and bta-miR-374b, and bta-miR-486) appear to specifically target elements involved in three major biological pathways.…”