Abstract
Phthalates are extensively used as plasticizers in a variety of daily-life products, resulting in widespread distribution in aquatic environments. However, limited information is available on the endocrine disrupting effects of phthalates in aquatic organisms. The aim of the present study was to examine whether exposure to mono-(2-ethylhexyl) phthalate (MEHP), the hydrolytic metabolite of di-(2-ethylhexyl) phthalate (DEHP) disrupts thyroid endocrine system in fish. In this study, zebrafish (Danio rerio) embryos were exposed to different concentrations of MEHP (1.6, 8, 40, and 200 μg/L) from 2 h post-fertilization (hpf) to 168 hpf. The whole-body content of thyroid hormone and transcription of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were examined. Treatment with MEHP significantly decreased whole-body T4 contents and increased whole-body T3 contents, indicating thyroid endocrine disruption. The upregulation of genes related to thyroid hormone metabolism (Dio2 and UGT1ab) might be responsible for decreased T4 contents. Elevated gene transcription of Dio1 was also observed in this study, which might assist to degrade increased T3 contents. Exposure to MEHP also significantly induced transcription of genes involved in thyroid development (Nkx2.1 and Pax8) and thyroid hormone synthesis (TSHβ, NIS and TG). However, the genes encoding proteins involved in TH transport (transthyretin, TTR) was transcriptionally significantly down-regulated after exposure to MEHP. Overall, these results demonstrate that acute exposure to MEHP alters whole-body contents of thyroid hormones in zebrafish embryos/larvae and changes the transcription of genes involved in the HPT axis, thus exerting thyroid endocrine toxicity.
Highlights
Phthalate esters are a group of industrial chemicals extensively used as plasticizers in a variety of commercial products, such as polyvinyl chloride (PVC) floors, food packaging, clothing, toys, films, paints, adhesives, lubricants, cosmetics, electronics, ink printers and biomedical devices [1,2]
Studies exploring the association between mono-(2-ethylhexyl) phthalate (MEHP) exposure and thyroid endocrine disrupting effects are limited, growing human studies have indicated that MEHP has the potential to alter thyroid hormone levels [28,29,30]
In the present study, developing zebrafish embryos/larvae were employed to assess effects of MEHP on thyroid hormone contents (T4 and T3) and mRNA expression related to thyroid hormones synthesis, secretion, transport and metabolism
Summary
Phthalate esters are a group of industrial chemicals extensively used as plasticizers in a variety of commercial products, such as polyvinyl chloride (PVC) floors, food packaging, clothing, toys, films, paints, adhesives, lubricants, cosmetics, electronics, ink printers and biomedical devices (e.g., blood transfusion bags) [1,2]. A recent study estimated that the worldwide production of phthalates reached 11 billion pounds every year [3]. Because they are not chemically bonded to the polymer, phthalates tend to release from the matrix with time and use [4]. MEHP has been detected in intravenous solutions stored in medical grade PVC bags [11], serum and plasma products packed into plastic containers and water from medical grade PVC tubing [12]. A recent study demonstrated that MEHP was detected in all sediment and soil samples ranged from 13.0 to 166.7 ng/g [14]. The potential health risks caused by DEHP/MEHP are receiving growing public concern
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