Titanium dioxide nanoparticles perturb the blood-testis barrier via disruption of actin-based cell adhesive function.
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ABSTRACT:
SUBMITTER: Ni DQ
PROVIDER: S-EPMC8714145 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This project utilized oligonucleotide microarrays to examine gene expression patterns in adult male fathead minnows (Pimephales promelas) exposed to a common nanomaterial, titanium dioxide (TiO2, stearate-coated particles, MT-100TV®). We exposed adult male fathead minnows for 96 hr to three doses (0, 1, and 10 mg/L nominal) of TiO2 under static renewal conditions. TiO2 is stearate coated, 15 nm particle size.
2010-12-22 | GSE17902 | GEO
Project description:This project utilized oligonucleotide microarrays to examine gene expression patterns in adult male fathead minnows (Pimephales promelas) exposed to a common nanomaterial, titanium dioxide (TiO2, stearate-coated particles, MT-100TV®). We exposed adult male fathead minnows for 96 hr to three doses (0, 1, and 10 mg/L nominal) of TiO2 under static renewal conditions. TiO2 is stearate coated, 15 nm particle size. Three-condition experiment: high dose, controls (untreated, low dose). Three tissues: liver, gill, brain. Biological replicates: 4 control replicates, 4 low dose, 4 high dose for gill and liver. One array for brain control and low dose; and 2 arrays for brain high dose. Contributor: Johnson & Johnson Worldwide Envrionmental
2010-12-22 | E-GEOD-17902 | biostudies-arrayexpress
Project description:Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in children worldwide. While most develop a mild, self-limiting illness, some develop severe acute lower respiratory infection and persistent airway disease. Exposure to ambient particulate matter has been linked to asthma, bronchitis, and viral infection in multiple epidemiological studies. We hypothesized that coexposure to nanoparticles worsens RSV-induced airway epithelial barrier dysfunction. Bronchial epithelial cells were incubated with titanium dioxide nanoparticles (TiO2-NP) or a combination of TiO2-NP and RSV. Structure and function of epithelial cell barrier were analyzed. Viral titer and the role of reactive oxygen species (ROS) generation were evaluated. In vivo, mice were intranasally incubated with TiO2-NP, RSV, or a combination. Lungs and bronchoalveolar lavage (BAL) fluid were harvested for analysis of airway inflammation and apical junctional complex (AJC) disruption. RSV-induced AJC disruption was amplified by TiO2-NP. Nanoparticle exposure increased viral infection in epithelial cells. TiO2-NP induced generation of ROS, and pretreatment with antioxidant, N-acetylcysteine, reversed said barrier dysfunction. In vivo, RSV-induced injury and AJC disruption were augmented in the lungs of mice given TiO2-NP. Airway inflammation was exacerbated, as evidenced by increased white blood cell infiltration into the BAL, along with exaggeration of peribronchial inflammation and AJC disruption. These data demonstrate that TiO2-NP exposure exacerbates RSV-induced AJC dysfunction and increases inflammation by mechanisms involving generation of ROS. Further studies are required to determine whether NP exposure plays a role in the health disparities of asthma and other lung diseases, and why some children experience more severe airway disease with RSV infection.
| S-EPMC7518063 | biostudies-literature
Project description:BackgroundDepending on their distinct properties, titanium dioxide nanoparticles (TiO2-NPs) are manufactured extensively and widely present in our daily necessities, with growing environmental release and public concerns. In sunscreen formulations, supplementation of TiO2-NPs may reach up to 25% (w/w). Ocular contact with TiO2-NPs may occur accidentally in certain cases, allowing undesirable risks to human vision. This study aimed to understand the barrier integrity of retinal endothelial cells in response to TiO2-NP exposure. bEnd.3 cells and human retinal endothelial cells (HRECs) were exposed to TiO2-NP, followed by examination of their tight junction components and functions.ResultsTiO2-NP treatment apparently induced a broken structure of the junctional plaques, conferring decreased transendothelial electrical resistance, a permeable paracellular cleft, and improved cell migration in vitro. This might involve rapid activation of metalloproteinase, a disintegrin and metalloproteinase 17 (ADAM17), and ADAM17-mediated claudin-5 degradation. For the in vivo study, C57BL/6 mice were administered a single dose of TiO2-NP intravitreally and then subjected to a complete ophthalmology examination. Fluorescein leakage and reduced blood flow at the optical disc indicated a damaged inner blood-retinal barrier induced by TiO2-NPs. Inappreciable change in the thickness of retinal sublayers and alleviated electroretinography amplitude were observed in the TiO2-NP-treated eyes.ConclusionsOverall, our data demonstrate that TiO2-NP can damage endothelial cell function, thereby affecting retinal electrophysiology.
| S-EPMC7796566 | biostudies-literature
Project description:In epithelia, a primary damage of tight junctions (TJ) always leads to a secondary disruption of adherens junction (AJ), and vice versa. This response, if occurring in the testis, would disrupt spermatogenesis because the blood-testis barrier (BTB) must remain intact during the transit of spermatids in the seminiferous epithelium, which is associated with extensive apical ectoplasmic specialization (apical ES, a testis-specific AJ type) restructuring. As such, apical ES restructuring accompanied with the transit of developing spermatids during spermiogenesis must be segregated from the BTB to avoid an immunological barrier breakdown in all stages of the seminiferous epithelial cycle, except at stage VIII when spermiation and BTB restructuring take place concurrently. We report herein a mechanism involving restricted spatial and temporal expression of Arp2/3 complex and N-WASP, whose actin branching activity associated with apical ES and BTB restructuring in the seminiferous epithelium. High expression of Arp3 at the apical ES was shown to correlate with spermatid movement and proper spermatid orientation. Likewise, high Arp3 level at the BTB associated with its restructuring to accommodate the transit of preleptotene spermatocytes at stage VIII of the epithelial cycle. These findings were validated by in vitro and in vivo studies using wiskostatin, an inhibitor that blocks N-WASP from activating Arp2/3 complex to elicit actin branching. Inhibition of actin branching caused a failure of spermatid transit plus a loss of proper orientation in the epithelium, and a "tightened" Sertoli cell TJ permeability barrier, supporting the role of Arp2/3 complex in segregating the events of AJ and BTB restructuring.
| S-EPMC2895132 | biostudies-literature
Project description:Synchrotron radiation (SR) X-ray has wide biomedical applications including high resolution imaging and brain tumor therapy due to its special properties of high coherence, monochromaticity and high intensity. However, its interaction with biological tissues remains poorly understood. In this study, we used the rat testis as a model to investigate how SR X-ray would induce tissue responses, especially the blood-testis barrier (BTB) because BTB dynamics are critical for spermatogenesis. We irradiated the male gonad with increasing doses of SR X-ray and obtained the testicles 1, 10 and 20 d after the exposures. The testicle weight and seminiferous tubule diameter reduced in a dose- and time-dependent manner. Cryosections of testes were stained with tight junction (TJ) component proteins such as occludin, claudin-11, JAM-A and ZO-1. Morphologically, increasing doses of SR X-ray consistently induced developing germ cell sloughing from the seminiferous tubules, accompanied by shrinkage of the tubules. Interestingly, TJ constituent proteins appeared to be induced by the increasing doses of SR X-ray. Up to 20 d after SR X-ray irradiation, there also appeared to be time-dependent changes on the steady-state level of these protein exhibiting differential patterns at 20-day after exposure, with JAM-A/claudin-11 still being up-regulated whereas occludin/ZO-1 being down-regulated. More importantly, the BTB damage induced by 40 Gy of SR X-ray could be significantly attenuated by antioxidant N-Acetyl-L-Cysteine (NAC) at a dose of 125 mg/kg. Taken together, our studies characterized the changes of TJ component proteins after SR X-ray irradiation, illustrating the possible protective effects of antioxidant NAC to BTB integrity.
| S-EPMC4581070 | biostudies-other
Project description:Earlier studies have shown that rats treated with an acute dose of 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide (adjudin, a male contraceptive under development) causes permanent infertility due to irreversible blood-testis barrier (BTB) disruption even though the population of undifferentiated spermatogonia remains similar to normal rat testes, because spermatogonia fail to differentiate into spermatocytes to enter meiosis. Since other studies have illustrated the significance of connexin 43 (Cx43)-based gap junction in maintaining the homeostasis of BTB in the rat testis and the phenotypes of Sertoli cell-conditional Cx43 knockout mice share many of the similarities of the adjudin-treated rats, we sought to examine if overexpression of Cx43 in these adjudin-treated rats would reseal the disrupted BTB and reinitiate spermatogenesis. A full-length Cx43 cloned into mammalian expression vector pCI-neo was used to transfect testes of adjudin-treated ratsversusempty vector. It was found that overexpression of Cx43 indeed resealed the Sertoli cell tight junction-permeability barrier based on a functionalin vivoassay in tubules displaying signs of meiosis as noted by the presence of round spermatids. Thus, these findings suggest that overexpression of Cx43 reinitiated spermatogenesis at least through the steps of meiosis to generate round spermatids in testes of rats treated with an acute dose of adjudin that led to aspermatogenesis. It was also noted that the round spermatids underwent eventual degeneration with the formation of multinucleated cells following Cx43 overexpression due to the failure of spermiogenesis because no elongating/elongated spermatids were detected in any of the tubules examined. The mechanism by which overexpression of Cx43 reboots meiosis and rescues BTB function was also examined. In summary, overexpression of Cx43 in the testis with aspermatogenesis reboots meiosis and reseals toxicant-induced BTB disruption, even though it fails to support round spermatids to enter spermiogenesis.-Li, N., Mruk, D. D., Mok, K.-W., Li, M. W. M., Wong, C. K. C., Lee, W. M., Han, D., Silvestrini, B., Cheng, C. Y. Connexin 43 reboots meiosis and reseals blood-testis barrier following toxicant-mediated aspermatogenesis and barrier disruption.
| S-EPMC4799501 | biostudies-literature
Project description:Exposure to titanium dioxide (TiO2) food additive by ingestion increased over the years. TiO2 is used in food to give a brighter, fresher colour to sweets, cookies, salad dressing under the name E171. New studies on E171 showed that after ingestion in a colorectal cancer mouse model, a significant increased number of colorectal tumours were found. In addition, short-term exposure to E171 induces gene expression changes in relation to oxidative stress responses, an impairment of the immune system, activation of signalling and cancer-related genes. Furthermore, dysregulation of the immune system was also observed after ingestion of E171 in rats. E171 comprises nanoparticles (NPs) and microparticles (MPs). Previous in vitro studies showed the capacity of E171, TiO2 NPs and MPs to induce oxidative stress, DNA damage, and induction of the micronuclei. The aim of our study was to investigate the relative contribution of the NPs and MPs fractions to the effects of E171 at the molecular level. This investigation was performed using in vitro exposure of Caco-2 cells to E171 as well as the NPs and MPs fractions of TiO2 and assessing effects with genome wide gene expression analysis. Results showed that the E171, TiO2 NPs and MPs induce gene expression changes in signalling, inflammation, immune system, transport, and cancer. Contribution of NPs was observed on genes involved in TLR cascade, MHC class I and II presentation, late cornified envelope, potassium channels, and cell cycle. MPs contribution was observed with changes in gene expression on a target to Hedgehog family, α-defensins, cadherin and cholinergic receptors. The gene expression changes associated with the immune system and inflammation induced by E171, MPs, and NPs suggest the creation of a favourable environment for cancer development.
2019-11-22 | GSE110410 | GEO
Project description:In recent years, various serious diseases caused by Zika virus (ZIKV) have made it impossible to be ignored. Confirmed existence of ZIKV in semen and sexually transmission of ZIKV suggested that it can break the blood-testis barrier (BTB), or Sertoli cell barrier (SCB). However, little is known about the underlying mechanism. In this study, interaction between actin, an important component of the SCB, and ZIKV envelope (E) protein domain III (EDIII) was inferred from co-immunoprecipitation (Co-IP) liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Confocal microscopy confirmed the role of actin filaments (F-actin) in ZIKV infection, during which part of the stress fibers, the bundles that constituted by paralleled actin filaments, were disrupted and presented in the cell periphery. Colocalization of E and reorganized actin filaments in the cell periphery of transfected Sertoli cells suggests a participation of ZIKV E protein in ZIKV-induced F-actin rearrangement. Perturbation of F-actin by cytochalasin D (CytoD) or Jasplakinolide (Jas) enhanced the infection of ZIKV. More importantly, the transepithelial electrical resistance (TEER) of an in vitro mouse SCB (mSCB) model declined with the progression of ZIKV infection or overexpression of E protein. Co-IP and confocal microscopy analyses revealed that the interaction between F-actin and tight junction protein ZO-1 was reduced after ZIKV infection or E protein overexpression, highlighting the role of E protein in ZIKV-induced disruption of the BTB. We conclude that the interaction between ZIKV E and F-actin leads to the reorganization of F-actin network, thereby compromising BTB integrity.
| S-EPMC8379325 | biostudies-literature
Project description:There is a high incidence of infertility in males following traumatic spinal cord injury (SCI). Quality of semen is frequently poor in these patients, but the pathophysiological mechanism(s) causing this are not known. Blood-testis barrier (BTB) integrity following SCI has not previously been examined. The objective of this study was to characterize the effects of spinal contusion injury on the BTB in the rat. 63 adult, male Sprague Dawley rats received SCI (n?=?28), laminectomy only (n?=?7) or served as uninjured, age-matched controls (n?=?28). Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), BTB permeability to the vascular contrast agent gadopentate dimeglumine (Gd) was assessed at either 72 hours-, or 10 months post-SCI. DCE-MRI data revealed that BTB permeability to Gd was greater than controls at both 72 h and 10 mo post-SCI. Histological evaluation of testis tissue showed increased BTB permeability to immunoglobulin G at both 72 hours- and 10 months post-SCI, compared to age-matched sham-operated and uninjured controls. Tight junctional integrity within the seminiferous epithelium was assessed; at 72 hours post-SCI, decreased expression of the tight junction protein occludin was observed. Presence of inflammation in the testes was also examined. High expression of the proinflammatory cytokine interleukin-1 beta was detected in testis tissue. CD68(+) immune cell infiltrate and mast cells were also detected within the seminiferous epithelium of both acute and chronic SCI groups but not in controls. In addition, extensive germ cell apoptosis was observed at 72 h post-SCI. Based on these results, we conclude that SCI is followed by compromised BTB integrity by as early as 72 hours post-injury in rats and is accompanied by a substantial immune response within the testis. Furthermore, our results indicate that the BTB remains compromised and testis immune cell infiltration persists for months after the initial injury.
| S-EPMC3027675 | biostudies-literature