Exosomes, endogenous retroviruses and toll-like receptors: pregnancy recognition in ewes

Ruiz-Gonzalez, Irene; Xu, Jing; Wang, Xiaoqiu; Burghardt, Robert C.; Dunlap, Kathrin A.; Bazer, Fuller W.

doi:10.1530/rep-14-0538

Cited by 102 publications

(98 citation statements)

References 55 publications

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“…We are exploring differences in these pathways, again considering that utilization of this information may derive potential biomarkers of fertility to support genetic gain in fertil-ity. We note with interest that some comparable initial experiments have been conducted in sheep (Cleys et al, 2014;Ruiz-Gonzalez et al, 2015). Our finding of altered immunologic pathway factors in the SUBFERT cows is consistent with views that infection or subclinical infection results in reduced fertility (Sheldon et al, 2008).…”

Section: Discussionsupporting

confidence: 87%

“…Furthermore, exosomes have recently been used as a marker for pregnancy and pregnancy-related pathologies in humans (Tsochandaridis et al, 2015). In sheep, exosomes derived from uterine flushings stimulate trophoectoderm cell lines to proliferate and secrete interferon tau, the pregnancy recognition signal (Ruiz-Gonzalez et al, 2015). The miRNA content of exosomes has also been characterized in bovine follicular fluid, with content differing depending on the oocytes stage of development (Sohel et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Plasma exosome profiles from dairy cows with divergent fertility phenotypes

Mitchell

Scholz-Romero

Reed

et al. 2016

Journal of Dairy Science

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Cell-to-cell communication in physiological and pathological conditions may be influenced by neighboring cells, distant tissues, or local environmental factors. Exosomes are specific subsets of extracellular vesicles that internalize and deliver their content to near and distant sites. Exosomes may play a role in the maternal-embryo crosstalk vital for the recognition and maintenance of a pregnancy; however, their role in dairy cow reproduction has not been established. This study aimed to characterize the exosome profile in the plasma of 2 strains of dairy cow with divergent fertility phenotypes. Plasma was obtained and characterized on the basis of genetic ancestry as fertile (FERT; <23% North American genetics, New Zealand Holstein-Friesian strain, n=8) or subfertile (SUBFERT; >92% North American genetics, North American Holstein-Friesian strain, n=8). Exosomes were isolated by differential and buoyant density centrifugation and characterized by size distribution (nanoparticle tracking analysis, NanoSight NS500, NanoSight Ltd., Amesbury, UK), the presence of CD63 (Western blot), and their morphology (electron microscopy). The total number of exosomes was determined by quantifying the immunoreactive CD63 (ExoELISA kit, System Biosciences), and the protein content established by mass spectrometry. Enriched exosome fractions were identified as cup-shape vesicles with diameters around 100 nm and positive for the CD63 marker. The concentration of exosomes was 50% greater in FERT cows. Mass spectrometry identified 104 and 117 proteins in FERT and SUBFERT cows, of which 23 and 36 were unique, respectively. Gene ontology analysis revealed enrichment for proteins involved in immunomodulatory processes and cell-to-cell communication. Although the role of exosomes in dairy cow reproduction remains to be elucidated, their quantification and content in models with divergent fertility phenotypes could provide novel information to support both physiological and genetic approaches to improving dairy cow fertility.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Plasma exosome profiles from dairy cows with divergent fertility phenotypes

Mitchell

Scholz-Romero

Reed

et al. 2016

Journal of Dairy Science

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“…IFN-τ down regulated oxytocin receptor through IRF-2. In pregnant ovine, exsomes stimulate trophecderm cells to proliferate and secrete IFN-τ with regulation of TLR- mediated cell signaling [9]. On the other hands, IFN-τ stimulated ISG through STAT1, STAT2 and IRF9 in immune cells like a PBMCs [8].…”

Section: Introductionmentioning

confidence: 99%

Change in the responsiveness of interferon-stimulated genes during early pregnancy in cows with Borna virus-1 infection

Takino

Okamura

Ando³

et al. 2016

BMC Vet Res

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BackgroundBorna disease virus is a neurotropic pathogen and infects the central nervous system. This virus infected a variety of animal species including cows. The most of cows infected with Borna disease virus 1 (BoDV-1) exhibit subclinical infection without any neurological symptoms throughout their lifetime. We previously reported on the low conception rates in-seropositive cows. Interferon-τ (IFN-τ) plays an important role in stable fertilization, and is produced from the fetal side following embryo growth at 15–40 days of pregnancy. IFN-τ induces the expression of interferon-stimulated gene (ISG) 15 and Mx2 in peripheral blood mononuclear cells (PBMCs). To understand the embryo growth and maternal reaction during early pregnancy in cows with BoDV-1 infection, we aimed to assess the gene expression of ISG15 and Mx2 from PBMCs in BoDV-1-seropositive cows.ResultsNone of the cows showed any clinical and neurological symptoms. Among the cows that conceived, the expressions of the ISG15 and Mx2 genes were greater in the BoDV-1-seropositive cows than in the BoDV-1-seronegative cows; the difference was significant between the cows that conceived and those that did not (P < 0.05).ConclusionsThe expression of ISG15 and Mx2 genes during early pregnancy significantly increased in the BoDV-1-seropositive cows and may be important for the maintenance of stable pregnancy in BoDV-1-infected cows. In contrast, the gene expression levels of ISG15 and Mx2 did not significantly increase during early pregnancy in BoDV-1-seronegative cows. Thus, BoDV-1 infection may lead to instability in the maintenance of early pregnancy by interfering with INF-τ production.

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“…The TLR-regulation of embryonic interferon-τ secretion was clearly shown in the ruminants (Ruiz-Gonzalez et al, 2015). Moreover, during early pregnancy, expression profiles of TLRs dramatically changed in both peripheral blood leukocytes (PBLs) and trophoblast cells of ewes (Kaya et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 2 and 4 expression in the bovine corpus luteum during the different stages of the estrous cycle

Atlı¹,

Köse²,

Kaya³

et al. 2017

Anim Reprod

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The aim of this study was to elucidate the presence of components of the innate immune system in the bovine corpus luteum (CL) by detecting the expression and cell-specific localization of TLR2 and TLR4 during different stages of the estrous cycle in a control study design. Bovine CL samples were collected from a local slaughterhouse and assigned to three groups as follows: developing CL (dCL; n = 6, approx. days 3-6), mature CL (mCL; n = 5, approx. days 8-12), and regressing CL (rCL; n = 5, approx. days 17-19). An upregulation of TLR2 mRNA was detected only in rCL (P < 0.05). Localization of the TLR2 protein was particularly apparent in luteal cells and a prominent immunofluorescent signal corresponding to TLR2 was detected only in rCL. TLR4 mRNA were higher in mCL and rCL compared to dCL (P < 0.05). The presence of the TLR4 protein in bovine CL was clearly detected in the luteal cells of both mCL and rCL. The results of this study suggest a role for TLRs in the development, maintenance, and regression of bovine CL. TLR signaling mediated pathway in luteal cells may involve in the regression of CL via regulation of TLR2 and TLR4.

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Exosomes, endogenous retroviruses and toll-like receptors: pregnancy recognition in ewes

Cited by 102 publications

References 55 publications

Plasma exosome profiles from dairy cows with divergent fertility phenotypes

Plasma exosome profiles from dairy cows with divergent fertility phenotypes

Change in the responsiveness of interferon-stimulated genes during early pregnancy in cows with Borna virus-1 infection

Toll-like receptor 2 and 4 expression in the bovine corpus luteum during the different stages of the estrous cycle

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