Biology subjects

Plavicki, J.

Publications and source records attributed to Plavicki, J..

4 recordsLinked to original sources

bioRxiv2023

Exposure to the aryl hydrocarbon receptor agonist dioxin disrupts formation of the muscle, nerves, and vasculature in the developing jaw

Human exposures to environmental pollutants can disrupt embryonic development and impact juvenile and adult health outcomes by adversely affecting cell and organ function. Notwithstanding, environmental contamination continues to increase because of industrial development, insufficient regulations, and the mobilization of pollutants due to extreme weather events. Dioxins are a class of structurally related persistent organic pollutants that are highly toxic, carcinogenic, and teratogenic. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent dioxin compound and has been shown to induce toxic effects in developing organisms by activating the aryl hydrocarbon receptor (AHR), a ligand activated transcription factor targeted by multiple persistent organic pollutants. Contaminant-induced AHR activation results in malformations in the craniofacial cartilages and neurocranium; however, the mechanisms mediating these phenotypes are not entirely understood. In this study, we utilized the optically transparent zebrafish model to elucidate novel transcriptional and structural targets of embryonic TCDD exposure leading to craniofacial malformations. To this end, we exposed zebrafish embryos at 4 hours post fertilization (hpf) to TCDD and employed a mixed-methods approach utilizing immunohistochemistry staining, transgenic reporter lines, fixed and in vivo confocal imaging, and timelapse microscopy to determine the targets mediating TCDD-induced craniofacial phenotypes. Our data shows that embryonic TCDD exposure reduced jaw and pharyngeal arch Sox10+ chondrocytes and Tcf21+ pharyngeal mesoderm progenitors. Exposure to TCDD correspondingly led to a reduction in collagen type II deposition in Sox10+ domains. Embryonic TCDD exposure impaired development of tissues derived from or guided by Tcf21+ progenitors, namely: nerves, muscle, and vasculature. Specifically, TCDD exposure disrupted development of the hyoid and mandibular arch muscles, decreased neural innervation of the jaw, resulted in compression of cranial nerves V and VII, and led to jaw vasculature malformations. Collectively, these findings reveal novel transcriptional and structural targets of TCDD-induced toxicity, showcasing how contaminant exposures lead to congenital craniofacial malformations. HighlightsO_LIEmbryonic TCDD exposure diminishes Sox10+ craniofacial chondrocytes. C_LIO_LIFollowing TCDD exposure Col2a1 deposition is reduced in Sox10+ domains. C_LIO_LIExposure to TCDD decreases Tcf21+ progenitors and impairs muscle formation. C_LIO_LITCDD exposure leads to defects jaw innervation and cranial nerve establishment. C_LIO_LIEarly TCDD exposure results in vasculature malformations in the jaw. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/546117v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@b803c4org.highwire.dtl.DTLVardef@ff4483org.highwire.dtl.DTLVardef@eafa18org.highwire.dtl.DTLVardef@c97dba_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2023

Building methodological consensus to ensure rigor and reproducibility in zebrafish fertility research

Zebrafish are an increasingly popular model for studying the genetic and environmental factors that shape male and female fertility; however, the field currently lacks a standardized approach to fertility assessment. The current lack of consensus makes comparisons across studies more challenging and is an obstacle to reproducibility in the fields of reproductive biology and toxicology. Here, we review the diversity of spawning approaches used in zebrafish reproductive toxicology research to asses fertility and provide evidence that spawning parameters can result in meaningful differences in egg production and spawning success. HighlightsO_LIZebrafish fertility research lacks methodological consensus C_LIO_LIMeasures of fertility vary with age and frequency of spawning C_LIO_LIMethodological consensus will increase reproducibility in toxicology C_LI

pharmacology and toxicology↗

bioRxiv2023

Exposure to the persistent organic pollutant 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin) disrupts development of the zebrafish inner ear

Dioxins are a class of highly toxic and persistent environmental pollutants that have been shown through epidemiological and laboratory-based studies to act as developmental teratogens. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most potent dioxin congener, has a high affinity for the aryl hydrocarbon receptor (AHR), a ligand activated transcription factor. TCDD-induced AHR activation during development impairs nervous system, cardiac, and craniofacial development. Despite the robust phenotypes previously reported, the characterization of developmental malformations and our understanding of the molecular targets mediating TCDD-induced developmental toxicity remains limited. In zebrafish, TCDD-induced craniofacial malformations are produced, in part, by the downregulation of SRY-box transcription factor 9b (sox9b), a member of the SoxE gene family. sox9b, along with fellow SoxE gene family members sox9a and sox10, have important functions in the development of the otic placode, the otic vesicle, and, ultimately, the inner ear. Given that sox9b in a known target of TCDD and that transcriptional interactions exist among SoxE genes, we asked whether TCDD exposure impaired the development of the zebrafish auditory system, specifically the otic vesicle, which gives rise to the sensory components of the inner ear. Using immunohistochemistry, in vivo confocal imaging, and time-lapse microscopy, we assessed the impact of TCDD exposure on zebrafish otic vesicle development. We found exposure resulted in structural deficits, including incomplete pillar fusion and altered pillar topography, leading to defective semicircular canal development. The observed structural deficits were accompanied by reduced collagen type II expression in the ear. Together, our findings reveal the otic vesicle as a novel target of TCDD-induced toxicity, suggest that the function of multiple SoxE genes may be affected by TCDD exposure, and provide insight into how environmental contaminants contribute to congenital malformations. HighlightsO_LIThe zebrafish ear is necessary to detect changes in motion, sound, and gravity. C_LIO_LIEmbryos exposed to TCDD lack structural components of the developing ear. C_LIO_LITCDD exposure impairs formation of the fusion plate and alters pillar topography. C_LIO_LIThe semicircular canals of the ear are required to detect changes in movement. C_LIO_LIFollowing TCDD exposure embryos fail to establish semicircular canals. C_LI

developmental biology↗

bioRxiv2022

High-resolution mass spectrometry reveals environmentally relevant uptake, elimination, and metabolic alterations following early embryonic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in zebrafish

Dioxin and dioxin-like compounds are ubiquitous environmental contaminants that induce toxicity by binding to the aryl hydrocarbon receptor (AHR), a ligand activated transcription factor. The zebrafish model has been used to define the developmental toxicity observed following exposure to exogenous AHR ligands such as the potent agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin, TCDD). While the model has successfully identified cellular targets of TCDD and molecular mechanisms mediating TCDD-induced phenotypes, fundamental information such as the body burden produced by standard exposure paradigms is still unknown. We performed targeted gas chromatography (GC) high-resolution mass spectrometry (HRMS) in tandem with non-targeted liquid chromatography (LC) HRMS to quantify TCDD uptake, model the elimination dynamics of TCDD, and determine how TCDD exposure affects the zebrafish metabolome. We found that 10 ppb, 1 ppb, and 50 ppt waterborne exposures during early embryogenesis produced environmentally relevant body burden of TCDD: 38 {+/-} 4.34, 26.6 {+/-} 1.2, and 8.53 {+/-} 0.341 pg/embryo, respectively, at 24 hours post fertilization. In addition, we discovered that TCDD exposure was associated with the dysregulation of several metabolic pathways that are critical for brain development and function including glutamate metabolism, chondroitin sulfate biosynthesis, and tyrosine metabolism pathways. Together, these data demonstrate that existing exposure paradigms produce environmentally relevant body burdens of TCDD in zebrafish and provide insight into the biochemical pathways impacted by toxicant-induced AHR activation. HIGHLIGHTSO_LIHistorical TCDD exposure paradigms produce environmentally relevant body burdens in zebrafish embryos. C_LIO_LITCDD elimination for high doses can be modeled using an exponential regression. C_LIO_LIExposure to TCDD alters metabolic pathways that are essential for brain development and function. C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/490602v2_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@17ba806org.highwire.dtl.DTLVardef@1543d58org.highwire.dtl.DTLVardef@1878204org.highwire.dtl.DTLVardef@168f21d_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗