Exposure to arsenic during embryogenesis impairs olfactory sensory neuron differentiation and function into adulthood

Abstract

Arsenic is a contaminant of food and drinking water. Epidemiological studies have reported correlations between arsenic exposure and neurodevelopmental abnormalities, such as reduced sensory functioning, while in vitro studies have shown that arsenic reduces neurogenesis and alters stem cell differentiation. The goal of this study was assess whether arsenic exposure during embryogenesis reduced olfactory stem cell function and/or numbers, and if so, whether those changes persist into adulthood. Killifish (Fundulus heteroclitus) embryos were exposed to 0, 10, 50 or 200 ppb arsenite (As III ) until hatching, and juvenile fish were raised in clean water. At 0, 2, 4, 8, 16, 28 and 40 weeks of age, odorant response tests were performed to assess specific olfactory sensory neuron (OSN) function. Olfactory epithelia were then collected for immunohistochemical analysis of stem cell (Sox2) and proliferating cell numbers (PCNA), as well as the number and expression of ciliated (calretinin) and microvillus OSNs (G αi3 ) at 0, 4, 16 and 28 weeks. Odorant tests indicated that arsenic exposure during embryogenesis increased the start time of killifish responding to pheromones, and this altered start time persisted to 40 weeks postexposure. Response to the odorant taurocholic acid (TCA) was also reduced through week 28, while responses to amino acids were not consistently altered. Immunohistochemistry was used to determine whether changes in odorant responses were correlated to altered cell numbers in the olfactory epithelium, using markers of proliferating cells, progenitor cells, and specific OSNs. Comparisons between response to pheromones and PCNA+ cells indicated that, at week 0, both parameters in exposed fish were significantly reduced from the control group. At week 28, all exposure are still significantly different than control fish, but now with higher PCNA expression coupled with reduced pheromone responses. A similar trend was seen in the comparisons between Sox2-expressing progenitor cells and response to pheromones, although Sox2 expression in the 28 *

Toxicological effects of As (V) in juvenile rockfish Sebastes schlegelii by a combined metabolomic and proteomic approach

“…The potential toxicity of As has received worldwide attention due to its frequent detection in the environment. As can stimulate numerous molecular events in connection with lipid metabolism disorder, immune system dysfunction, oxidative stress and carcinogenesis in organisms, which have been well documented in a variety of organisms (Chen et al, 2018a,b;Chen et al, 2019;Ramsey et al, 2013;Szymkowicz et al, 2019;Xu et al, 2013;Yu et al, 2016). Since researchers often take advantage of traditional toxicological approaches to focus on a known class of toxicity-responsive molecules to draw out the toxic mechanisms, it is reluctant to discover new biological molecules associated with toxicological effects and presents initial and less comprehensive evaluations on toxicological reactions of pollutants in organisms (Ji et al, 2014).…”

Impact of Copper Nanoparticles and Copper Ions on Transcripts Involved in Neural Repair Mechanisms in Rainbow Trout Olfactory Mucosa

“…Nevertheless, some anthropogenic contaminants can interfere with olfactory neuroepithelial regenerative capability, and consequently inhibit the neuroepithelium reestablishment (Szymkowicz et al, 2019;Wang et al, 2017a).…”

Gestational Arsenic Trioxide Exposure Acts as a Developing Neuroendocrine-Disruptor by Downregulating Nrf2/PPARγ and Upregulating Caspase-3/NF-ĸB/Cox2/BAX/iNOS/ROS

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