Ecotoxicological Effects Of The Endocrine Disrupter Bisphenol A On Caenorhabditis Elegans And Its Mechanism Of Action

Bisphenol A (BPA), one of the recognized enviromental endocrine disruptors in the world, has been a hot area in the toxicological research. The demanded quantity of BPA is exceeding 4 million tons per year. The environmental pollution is becoming more and more serious, and BPA could be detected in the soil, water, air and sediment, even in the samples of the body’s tissues and fluids. In vivo and in vitro experiments have already proven that BPA could cause multiple effects including reproductive toxicity, developmental toxicity, neurotoxicity, and immunotoxicity. Population epidemiological studies have also found BPA exposure was closely associated with diabetes, obesity, neurobehavioral disorders, liver function abnormalities, recurrent abortion and developmental disorders.The literature about the effects of BPA exposure on invertebrates is limited. As a representative species isolated from the soil, the model animal of C. elegans is widely used in the environmental exposure assessment and ecological toxicology research. Ecotoxicological evaluations were conducted using C. elegans at the physiological, biochemical, and molecular levels, to assess the acute and subacute exposures, long-term exposure and multigenerational exposure of BPA. In addition, BPS (a replacement for BPA) toxicity was also evaluated. The results were compared with BPA toxicity to assess the potential ecological risks of BPA alternatives. The main results are as follows:(1) Acute and subacute exposures to BPA could significantly decrease the body length, locomotion behaviours and brood size of exposed C. elegans, and increased the cell apoptosis degree and stress-related genes expressions. Head thrash was the most sensitive endpoint by acute exposure to BPA, and the toxicity could be detected as low as 0.01 μM. After subacute exposure, body length and head thrash were more sensitive than other endpoints, and the toxicity could also be detected as low as 0.01 μM. Acute and subacute exposures could have no significant effects on the lipofuscin accumulation and ROS production, but the cell apoptosis degree significantly increased at concentrations above 0.1 μM. The results indicated that adverse physiological effects induced by BPA exposure should not result from oxidative stress, and the negative consequences were probably due to increased cell apoptosis. Subacute exposure to BPA could lead to the significant increases in the expression of most stress-related genes. Even at the lowest concentration of 0.001 μM, BPA exposure could also induce the obvious alterations in most of selected genes.(2) Long-term exposure to BPA could significantly decrease the body length, locomotion behaviours, lifespan and population size, and increase the cell apoptosis degree, stress-related genes expressions and stress response in the transgenic line TJ375. Head thrash was most sensitive among the tested endpoints for assessing the chronic toxicity of BPA, and the detection limit could be as low as 0.001 μM. Long-term exposure had no significant effects on the lipofuscin accumulation, but the cell apoptosis degree significantly increased at concentrations above 0.01 μM. Chronic exposure led to the significant increases in the mRNA levels of most genes at the tested concentrations. Compared to the subacute exposure, the chronic exposure induced more obvious increases in the tested genes expressions at the same exposure concentration. Compared to the control, the population size of the exposed C. elegans significantly decreased at the treatment groups from 0.1 μM to 10 μM. The transgenic nematode TJ375 was able to detect BPA toxicity in the environment with concentrations more than 1 μM, and seemed not sensitive towards BPA exposure compared to other endpoints.(3) Multigenerational exposure to BPA could have significant negative effects on the physiological indicators of exposed C. elegans at concentrations above 0.01 μM. As for each trait tested, the first generation response could be commonly mirrored in the subsequent generations at the highest concentration of 10 μM. However, at lower concentrations, the response of parental generation was a relatively poor predictor of the effects on progeny, as acclimation or cumulative damage could occur in the subsequent generations. In both G1 and G4 generations, the gene expressions at lower concentrations were more significantly affected than those at higher concentrations. Moreover, the integrated gene expression profiles visually demonstrated that BPA exposure induced more obvious increases of selected genes expressions in the Gi generation than in the G4 generation.(4) After subacute exposure to BPS, head thrash was more sensitive than other endpoints and showed significant decreases at 1 and 10 μM. With regard to other endpoints, significant decreases were only detected at the highest concentration. BPS would not induce obvious oxidative stress in C. elegans at the exposure concentrations in this study, and signicantly increased the degree of cell apoptosis only at 1 μM. BPS exposure was able to induce a small but significant increase in the mRNA levels of most genes at the tested concentrations.In conclusion, low-concentration BPA exposure was able to impose developmental, neurobehavioral and reproductive toxicities on C. elegans. The adverse physiological effects induced by BPA exposures were probably due to increased cell apoptosis. BPA exposure significantly increased the expressions of stress-related genes, and disrupted the homeostasis in C. elegans. The transgenic line TJ375 was not sensitive to BPA exposure, and could not be used to monitor BPA toxicity. Compared with BPA toxicity, BPS was less noxious.