Papers by Tisha King-Heiden
Toxicological Sciences, 2005
The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent endocrine disru... more The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent endocrine disruptor with the ability to affect several biologic processes, including reproduction. In fish, sublethal exposure to TCDD is known to modulate overall reproductive capacity, but impacts on follicular development and vitellogenesis are unknown. Here we show that chronic, dietary exposure to 0.08, 0.32, or 0.80 ng TCDD female ÿ1 day ÿ1 decreased egg production by more than 50% and that spawning success was reduced by as much as 96%. Serum estradiol concentrations were decreased more than twofold, accounting, in part, for observed decreases in serum vitellogenin concentrations by as much as 29%. Our data suggest that decreased egg production is likely the result of TCDD-mediated inhibition of the transition from pre-vitellogenic stage follicles to vitellogenic stage follicles, as well as the induction of follicular atresia. The majority of reproductive toxicity of TCDD is likely due to direct impacts on the ovary, yet histopathologic observations suggest liver toxicity could also contribute to observed impacts on vitellogenesis. Importantly, even when overall egg production is not significantly affected, our data show that subtle physiologic changes induced by TCDD can lead to altered gonadogenesis. This suggests that longterm exposure to very low concentrations of TCDD could greatly affect fecundity and reproductive success in fishes.
Environmental Science & Technology, 2013
Once released into the environment, engineered nanoparticles (eNPs) are subjected to processes th... more Once released into the environment, engineered nanoparticles (eNPs) are subjected to processes that may alter their physical or chemical properties, potentially altering their toxicity vis-à-vis the as-synthesized materials. We examined the toxicity to zebrafish embryos of CdSe core /ZnS shell quantum dots (QDs) before and after exposure to an in vitro chemical model designed to simulate oxidative weathering in soil environments based on a reductant-driven Fenton's reaction. Exposure to these oxidative conditions resulted in severe degradation of the QDs: the Zn shell eroded, Cd 2+ and selenium were released, and amorphous Se-containing aggregates were formed. Weathered QDs exhibited higher potency than did as-synthesized QDs. Morphological endpoints of toxicity included pericardial, ocular and yolk sac edema, non-depleted yolk, spinal curvature, tail malformations, and craniofacial malformations. To better understand the selenium-like toxicity observed in QD exposures, we examined the toxicity of selenite, selenate and amorphous selenium nanoparticles (SeNPs). Selenite exposures resulted in high mortality to embryos/larvae while selenate and SeNPs were non-toxic. Co-exposures to SeNPs + CdCl 2 resulted in dramatic increase in mortality and recapitulated the morphological endpoints of toxicity observed with weathered QD exposures. Cadmium body burden was increased in larvae exposed to weathered QDs or SeNP + CdCl 2 suggesting the increased potency of weathered QDs was due to selenium modulation of cadmium toxicity. Our findings highlight the need to examine the toxicity of eNPs after they have undergone environmental weathering processes.
Toxicological Sciences, 2009
Little is understood regarding the impacts of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure... more Little is understood regarding the impacts of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure during early development on the health, survival, and reproductive capability of adults. Here we use zebrafish to determine whether early life stage exposure to TCDD induces toxicity in adult zebrafish and their offspring. Zebrafish were exposed to graded concentrations of TCDD (0-400 pg/ml) via waterborne exposure for 1 h/week from 0 to 7 weeks of age. The heart and swim bladder were identified as being most sensitive to TCDD exposure during early development. Subtle developmental toxic responses collectively impaired survival, and only zebrafish in the 0, 25, and 50 pg TCDD/ml groups survived to adulthood. Surviving fish exhibited TCDD toxicity in craniofacial structures (i.e., operculum and jaw), heart, swim bladder, and ovary. Exposure to 25 pg TCDD/ml impaired egg production (40% of control), fertility (90% of control), and gamete quality. TCDDtreated males contributed more than females to impaired reproductive capacity. Transgenerational effects were also discovered in that offspring from parents exposed to TCDD during early life stages showed a 25% increase in mortality compared with the F1 of dimethyl sulfoxide fish, reduced egg production (30-50% of control) and fertility (96% of control). Thus, adverse effects resulting from TCDD exposure during early life stages for one generation of zebrafish were sufficient to cause adverse health and reproductive effects on a second generation of zebrafish. In the environment, transgenerational effects such as these may contribute to population declines for the most TCDD sensitive fish species.
Hydrobiologia, 2018
Environmental risk from contaminated aquatic sediments requires an understanding of its spatial d... more Environmental risk from contaminated aquatic sediments requires an understanding of its spatial distribution, bioavailability and rate of transfer to resident aquatic and terrestrial biota. We hypothesized that macroinvertebrates play a role in the sequestration, distribution, and dispersal of lead from lead shot contaminated sediments. To assess this, we sampled the predominant aquatic macroinvertebrate, Leptocerus americanus, from sites within the La Crosse River Marsh (La Crosse, Wi) identified to contain high levels of lead contamination. We measured lead content in larval cases, larval tissues and emergent adult tissues. Lead concentrations within whole larvae correlated with levels of lead within sediments, and lead was differentially partitioned between larval tissue and their silk cases. Over 90% of the lead was retained in larval cases, while the rest was distributed to the body tissue, which was largely conserved during the process of metamorphosis. Our models support that L. americanus emerging from the marsh in the contaminated area transfer as much as 160 mgPb out of the aquatic habitat each year. Our work demonstrates that macroinvertebrates affect the mobilization and dispersal of contaminants within aquatic sediments, and this role should be evaluated when making management decisions regarding contaminated ecosystems.
Current trends in endocrinology
Environmental contaminants are known to exert endocrine-disrupting effects on the reproductive ax... more Environmental contaminants are known to exert endocrine-disrupting effects on the reproductive axis of animals. Many of these molecules can affect steroid biosynthesis or estrogen-receptor signaling by behaving as estrogen-like molecules ("xenoestrogens"), or by exerting estrogenmodulatory effects. Exposure to some compounds has been correlated with the skewing of sex ratios in aquatic species, feminization and demasculinization of male animals, declines in human sperm counts, and overall diminution in fertility of birds, fish, and mammals. We herein devote space to several classes of endocrine-disrupting compounds (EDCs), including estrogenic substances such as bisphenol A (BPA), molecules that can behave at times anti-estrogenically while activating the aromatic hydrocarbon receptor (AHR), such as dioxins (a known human carcinogen), and novel, ubiquitous molecules such as nanoparticles, particularly gold nanoparticles (GNPs), that appear to alter the sexsteroid biosynthe...
Zebrafish, 2016
Triclosan (TCS) is an antimicrobial agent found in personal care products that has become prevale... more Triclosan (TCS) is an antimicrobial agent found in personal care products that has become prevalent in surface waters. TCS readily bioaccumulates within aquatic organisms, and has been found to be toxic to fish. In larval fishes, exposure to TCS disrupts a variety of developmental processes, impairs hatching success, and causes pericardial edema. In mammals, TCS exposure disrupts excitation-contraction-coupling in cardiac cells, which is associated with reductions in cardiac output. Here, we examine the impacts of TCS on heart function to better understand potential risks that TCS may pose to wild fish. Zebrafish were exposed to 0, 0.4, 40, and 400 μg TCS/L from 8 to 120 h postfertilization via static waterborne exposure with daily renewal. We examined the incidence of pericardial edema, and the impacts on heart structure and heart function. While incidence of pericardial edema increased following exposure to ≥40 μg TCS/L and the structure of the heart was altered, cardiac output was only reduced following exposure to 400 μg TCS/L. A small but significant proportion of embryos showed increased incidence of regurgitation following exposure to ≥0.4 μg TCS/L. Our findings suggest that acute exposure to TCS has the potential to cause subtle cardiac toxicity in developing fish, and further evaluation of the risks TCS pose to wild fish and human health is needed.
Molecular and Cellular …, 2011
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin) is a global environmental contaminant and th... more 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin) is a global environmental contaminant and the prototypical ligand for investigating aryl hydrocarbon receptor (AHR)-mediated toxicity. Environmental exposure to TCDD results in developmental and reproductive toxicity in fish, birds and mammals. To resolve the ecotoxicological relevance and human health risks posed by exposure to dioxin-like AHR agonists, a vertebrate model is needed that allows for toxicity studies at various levels of biological organization, assesses adverse reproductive and developmental effects and establishes appropriate integrative correlations between different levels of effects. Here we describe the reproductive and developmental toxicity of TCDD in feral fish species and summarize how using the zebrafish model to investigate TCDD toxicity has enabled us to characterize the AHR signaling in fish and to better understand how dioxin-like chemicals induce toxicity. We propose that such studies can be used to predict the risks that AHR ligands pose to feral fish populations and provide a platform for integrating risk assessments for both ecologically relevant organisms and humans.
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Papers by Tisha King-Heiden