Controlled ovarian hyperstimulation induced changes in the expression of circulatory miRNA in bovine follicular fluid and blood plasma

Background

Despite its role in increasing the number of offspring during the lifetime of an individual animal, controlled ovarian hyperstimulation (COH) may have detrimental effects on oocyte development, embryo quality and endometrial receptivity. Circulating miRNAs in bio-fluids have been shown to be associated with various pathological conditions including cancers. Here we aimed to investigate the effect of COH on the level of extracellular miRNAs in bovine follicular fluid and blood plasma and elucidate their mode of circulation and potential molecular mechanisms to be affected in the reproductive tract.

Method

Twelve simmental heifers were estrous synchronized and six of them were hyperstimulated using FSH. Follicular fluid samples from experimental animals were collected using ovum pick up technique at day 0 of the estrous cycle and blood samples were collected at day 0, 3 and 7 of post ovulation. The expression profile of circulatory miRNAs in follicular fluid and blood plasma were performed using the human miRCURY LNA? Universal RT miRNA PCR array system. A comparative threshold cycle method was used to determine the relative abundance of the miRNAs.

Results

A total of 504 and 402 miRNAs were detected in both bovine follicular fluid and blood plasma, respectively. Of these 57 and 21 miRNAs were found to be differentially expressed in follicular fluid and blood plasma, respectively derived from hyperstimulated versus unstimulated heifers. Bioinformatics analysis of those circulating miRNAs indicated that their potential target genes are involved in several pathways including TGF-beta signaling pathway, MAPK signaling pathway, pathways in cancer and Oocyte meiosis.Moreover, detail analysis of the mode of circulation of some candidates showed that most of the miRNA were found to be detected in both exosomal and Ago2 protein complex fraction of both follicular fluid and blood plasma.

Conclusion

Our data provide the consequence of hyperstimulation induced changes of extracellular miRNAs in bovine follicular fluid and blood plasma, which may have a potential role in regulating genes associated not only with bovine ovarian function but also involved in altering various physiological in bovine oocytes, embryos and modulating reproductive tract environment.

     

Description of Six Cases of Child Cauda Equina Leptomeningitis: An Emerging Disease

Child cauda equina leptomeningitis (CCEL) is a typical clinical example of aseptic meningitis with patterns of an emerging disease, and it affects children aged 2–9. Here we will describe six cases of CCEL. After the prodromes, all children underwent an acute phase with hypoasthenia of the lower limbs, hyporeflexia, staggering and ataxia with steppage. Only in one case there were generalized fits and coma of grade 1–2 too. All children underwent a spinal Magnetic Resonance Imaging (MRI), proving pathologic enhancement of cauda equina and conus medullaris leptomeningitis. At the same time, MRI made possible the differential diagnosis between cauda equina leptomeningitis and isolated minor forms of Guillain-Barre syndrome involving the lower limbs.

Three hypotheses will be formulated for understanding the pathogen mechanism(s) of CCEL. The first one is based on the presence of an immediate viral damage on the meninges, the second one, the more likely, contemplates the occurrence of an immunomediated mechanism in a host genetically prone to react in an abnormal way from an immune viewpoint. The third hyphotesis consists in a two-time damage: an early immediate damage from the virus, and a later immunomediated reaction.     

Narrative Medicine to integrate patients’, caregivers’ and clinicians’ migraine experiences: the DRONE multicentre project

Neurological Sciences - Although migraine is widespread and disabling, stigmatisation and poor awareness of the condition still represent barriers to effective care; furthermore, research on...     

Evaluation of diagnostic criteria and red flags of myelin oligodendrocyte glycoprotein encephalomyelitis in a clinical routine cohort

AimsMyelin oligodendrocyte glycoprotein antibodies (MOG‐IgG) have been proposed to define “MOG encephalomyelitis” (MOG‐EM), with published diagnostic and “red flag” criteria. We aimed to evaluate these criteria in a routine clinical setting.MethodsWe retrospectively analyzed patients with borderline/positive MOG‐IgG and applied the diagnostic and red flag criteria to determine likelihood of MOG‐EM diagnosis. Para‐/clinical parameters were described and analyzed with chi‐square test.ResultsIn total, 37 patients fulfilled MOG‐EM diagnostic criteria (female‐to‐male ratio: 1.6:1, median onset age: 28.0 years [IQR 18.5‐40.5], n = 8 with pediatric onset). In 24/37, red flags were present, predominantly MOG‐IgG at assay cutoff and/or MRI lesions suggestive of multiple sclerosis (MS). As proposed in the consensus criteria, these patients should rather be described as “possible” MOG‐EM. Of these, we classified 13 patients as “unlikely” MOG‐EM in the presence of the red flag “borderline MOG‐IgG” with negative MOG‐IgG retest or coincidence of ≥1 additional red flag. This group mainly consisted of patients diagnosed with MS (n = 11). Frequency of cerebrospinal fluid (CSF‐)—specific oligoclonal bands (OCB) is significantly lower in definite vs possible and unlikely MOG‐EM (P = .0005).ConclusionEvaluation of diagnostic and red flag criteria, MOG‐IgG retesting (incl. change of assay), and CSF‐specific OCB are relevant in clinical routine cohorts to differentiate MOG‐EM from MS.     

Homocysteine plasma levels in patients with migraine with aura

We investigated homocysteine plasma levels in 136 MA sufferers and in 117 sex-and age-matched controls. Mean homocysteine plasma levels — as well as the proportion of subjects with hyperhomocysteinaemia — were significantly higher in patients with MA than in healthy controls. Hyperhomocysteinaemia may be a link between MA and ischaemic stroke.