Biomol Ther.
2018 Sep;26(5):512-519. 10.4062/biomolther.2018.076.
Low Dose Exposure to Di-2-Ethylhexylphthalate in Juvenile Rats Alters the Expression of Genes Related with Thyroid Hormone Regulation
- Affiliations
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- 1College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea. kmlim@ewha.ac.kr
- 2Developmental and Reproductive Toxicology Research Group, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea.
- 3Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. kitaek@yuhs.ac
- 4Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
- 5GENECAST Co., Seongnam 05838, Republic of Korea.
- 6Department of Epidemiology and Health Promotion, and Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul 03722, Republic of Korea.
- 7Lab frontier Co., Anyang 14042, Republic of Korea.
- KMID: 2421730
- DOI: http://doi.org/10.4062/biomolther.2018.076
Abstract
- Phthalates widely used in the manufacture of plastics have deeply penetrated into our everyday lives. Recently, a concern over the toxicity of phthalates on thyroid, has been raised but in most of cases, the doses employed were unrealistically high. To investigate the effects of phthalates on thyroid, we investigated the effects of the repeated oral exposure to low to high doses (0.3, 3, 30 and 150 mg/kg) di-2-ethylhexylphthalate (DEHP) from weaning to maturity for 90 days in juvenile rats on the thyroid. The histological examination revealed that DEHP significantly induced hyperplasia in the thyroid from the doses of 30 mg/kg, which was confirmed with Ki67 staining. In line with this finding, increased mRNA expression of thyrotropin releasing hormone (Trh) was observed in the thyroid of female at 0.3 mg/kg and 150 mg/kg as determined by RNAseq analysis. Moreover, significantly increased expression of parathyroid hormone (Pth) in the female at 0.3 mg/kg, and thyroglobulin (Tg) and thyroid hormone responsive (Thrsp) in the male at 0.3 mg/kg were noted in the blood, of which changes were substantially attenuated at 150 m/kg, alluding the meaningful effects of low dose DEHP on the thyroid hormone regulation. Urinary excretion of mono-2-ethylhexyl-phthalate (MEHP), a major metabolite of DEHP was determined to be 4.10 and 12.26 ppb in male, 6.65 and 324 ppb in female at 0.3 and 30 mg/kg DEHP, respectively, which fell within reported human urine levels. Collectively, these results suggest a potential adverse effects of low dose phthalates on the thyroid.
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