Environmentally relevant uptake, elimination, and metabolic changes following early embryonic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in zebrafish

Kossack, Michelle E.; Manz, Katherine E.; Martin, Nathan R.; Pennell, Kurt D.; Plavicki, Jessica

doi:10.1016/j.chemosphere.2022.136723

Cited by 11 publications

(8 citation statements)

References 110 publications

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“…Newly fertilized embryos were exposed to TCDD for 1 h at 4 hpf. Due to its lipophilic nature, TCDD is readily absorbed during the exposure window and remains detectable as the parent compound at 72 hpf ( Kossack et al, 2023 ). We collected and analyzed samples at 48 hpf, a time point at which Ahr2 is still broadly expressed in the brain and biomarkers of AHR induction, including cyp1a1 , cyp1b1 , and cyp1c1 , are detected in CNS following TCDD exposure (( Andreasen et al, 2002 ; Yin et al, 2008 ; Jenny et al, 2009 ; Kubota et al, 2011 ).…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, lack of consistent stock and treatment solution validation could account for phenotypic variations following TCDD exposures. As such, TCDD stock solutions were validated as according to Kossack et al (2023) .…”

Section: Methodsmentioning

confidence: 99%

“…2,3,7,8-tetrachlorodibenzo-[p]-dioxin (TCCD, dioxin) stock preparation and exposure TCDD exposures were performed as described by Plavicki et al (2013). TCDD (ED-901-B, Cerriliant, St. Louis, MO) stock solutions were prepared by diluting 50.00 ± 0.32 μg/ml TCDD with pure dimethyl sulfoxide (DMSO) to a final concentration of 9.973 ± 0.223 μg/ml as reported in Kossack et al (2023). Stock solutions were prepared in 2 ml amber vials and caps were…”

Section: Zebrafish Husbandrymentioning

confidence: 99%

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Proper modulation of AHR signaling is necessary for establishing neural connectivity and oligodendrocyte precursor cell development in the embryonic zebrafish brain

Martin

Patel

Kossack

et al. 2022

Front. Mol. Neurosci.

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2,3,7,8-tetrachlorodibenzo-[p]-dioxin (TCDD) is a persistent global pollutant that exhibits a high affinity for the aryl hydrocarbon receptor (AHR), a ligand activated transcription factor. Epidemiological studies have associated AHR agonist exposure with multiple human neuropathologies. Consistent with the human data, research studies using laboratory models have linked pollutant-induced AHR activation to disruptions in learning and memory as well as motor impairments. Our understanding of endogenous AHR functions in brain development is limited and, correspondingly, scientists are still determining which cell types and brain regions are sensitive to AHR modulation. To identify novel phenotypes resulting from pollutant-induced AHR activation and ahr2 loss of function, we utilized the optically transparent zebrafish model. Early embryonic TCDD exposure impaired embryonic brain morphogenesis, resulted in ventriculomegaly, and disrupted neural connectivity in the optic tectum, habenula, cerebellum, and olfactory bulb. Altered neural network formation was accompanied by reduced expression of synaptic vesicle 2. Loss of ahr2 function also impaired nascent network development, but did not affect gross brain or ventricular morphology. To determine whether neural AHR activation was sufficient to disrupt connectivity, we used the Gal4/UAS system to express a constitutively active AHR specifically in differentiated neurons and observed disruptions only in the cerebellum; thus, suggesting that the phenotypes resulting from global AHR activation likely involve multiple cell types. Consistent with this hypothesis, we found that TCDD exposure reduced the number of oligodendrocyte precursor cells and their derivatives. Together, our findings indicate that proper modulation of AHR signaling is necessary for the growth and maturation of the embryonic zebrafish brain.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Zebrafish Husbandrymentioning

confidence: 99%

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Proper modulation of AHR signaling is necessary for establishing neural connectivity and oligodendrocyte precursor cell development in the embryonic zebrafish brain

Martin

Patel

Kossack

et al. 2022

Front. Mol. Neurosci.

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“…Zebrafish Rearing: Zebrafish (Danio rerio) were raised as described in Kossack et al and Westerfield (22,23). Larvae were placed in tanks at 5 dpf in 100mL rotifer culture, 400mL of fish water static, and one drop of RG Complete (Reef Nutrition).…”

Section: Methodsmentioning

confidence: 99%

Defining the cellular complexity of the zebrafish bipotential gonad

Kossack

Tian

Bowie

et al. 2023

Preprint

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Zebrafish are routinely used to model reproductive development, function, and disease, yet we still lack an understanding of the fundamental steps that occur during early bipotential gonad development, including when stromal cells invade the bipotential gonad to support gonad growth and differentiation. Here, we use a combination of transgenic reporters and single-cell sequencing analyses to define the arrival of different stromal cell types to the larval zebrafish gonad. We determined that blood arrives to the gonad via the gonadal artery, which is derived from the swim bladder artery. We find that vascular and lymphatic development occurs concurrently in the bipotential gonad and our data suggest that, similar to what has been observed in developing zebrafish embryo, lymphatic endothelial cells can be derived from vascular endothelial cells. Although we established that pdgfrb expression is not exclusive to ovarian pericytes, we can resolve that pdgfrb+ pericytes support the migration of endothelial tip cells within the ovary. We observed that macrophage are the first stromal cell type to populate the zebrafish gonad, establishing a nascent resident population as early as 12 dpf. Further, macrophage are responsible for removing cellular material, particularly during sex differentiation. This foundational information demonstrates that the early bipotential gonad contains complex cellular interactions which may shape the health and function of the later gonad.

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“…To examine how early embryonic exposure to TCDD affects otic development, we exposed zebrafish embryos carrying a transgenic reporter for sox10 , an early neural crest marker required for development of the otic vesicle epithelium as well as the peripheral nervous system, melanocytes, heart, and jaw (Dutton et al, 2009). Embryos were exposed to a 1-hour waterborne exposure of 10 parts-per-billion (ppb) TCDD at 4 hpf, an exposure paradigm that results in an internal body burden of 14.7 ±2.04 pg/embryo at 48 hpf and 9.78 ±1.31 pg/embryo at 72 hpf respectively (Kossack, Manz, Martin, Pennell, & Plavicki, 2023). Using confocal microscopy of fixed and live samples, we characterized the effects of exposure on otic vesicle morphology, quantifying fusion plate formation and pillar topography.…”

Section: Introductionmentioning

confidence: 99%

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

Cintrón-Rivera¹,

Oulette²,

Prakki³

et al. 2023

Preprint

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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 is 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.

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Environmentally relevant uptake, elimination, and metabolic changes following early embryonic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in zebrafish

Cited by 11 publications

References 110 publications

Proper modulation of AHR signaling is necessary for establishing neural connectivity and oligodendrocyte precursor cell development in the embryonic zebrafish brain

Proper modulation of AHR signaling is necessary for establishing neural connectivity and oligodendrocyte precursor cell development in the embryonic zebrafish brain

Defining the cellular complexity of the zebrafish bipotential gonad

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

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