Low dose exposure to Di-2-ethylhexylphthalate in Juvenile rats alters the expression of genes related with thyroid hormone regulation

Minjeong Kim, Ji Seong Jeong, Hyunji Kim, Seungwoo Hwang, Il Hyun Park, Byung Chul Lee, Sung Il Yoon, Sun Ha Jee, KiTaek Nam, Kyung Min Lim

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)512-519
Number of pages8
JournalBiomolecules and Therapeutics
Volume26
Issue number5
DOIs
Publication statusPublished - 2018 Sep 1

Fingerprint

Diethylhexyl Phthalate
Thyroid Hormones
Rats
Thyroid Gland
Genes
Gene Expression
Thyrotropin-Releasing Hormone
Thyroglobulin
Metabolites
Parathyroid Hormone
Toxicity
Weaning
Blood
Plastics
Hyperplasia
Messenger RNA
Urine
phthalic acid
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

Cite this

Kim, Minjeong ; Jeong, Ji Seong ; Kim, Hyunji ; Hwang, Seungwoo ; Park, Il Hyun ; Lee, Byung Chul ; Yoon, Sung Il ; Jee, Sun Ha ; Nam, KiTaek ; Lim, Kyung Min. / Low dose exposure to Di-2-ethylhexylphthalate in Juvenile rats alters the expression of genes related with thyroid hormone regulation. In: Biomolecules and Therapeutics. 2018 ; Vol. 26, No. 5. pp. 512-519.
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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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Low dose exposure to Di-2-ethylhexylphthalate in Juvenile rats alters the expression of genes related with thyroid hormone regulation. / Kim, Minjeong; Jeong, Ji Seong; Kim, Hyunji; Hwang, Seungwoo; Park, Il Hyun; Lee, Byung Chul; Yoon, Sung Il; Jee, Sun Ha; Nam, KiTaek; Lim, Kyung Min.

In: Biomolecules and Therapeutics, Vol. 26, No. 5, 01.09.2018, p. 512-519.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Low dose exposure to Di-2-ethylhexylphthalate in Juvenile rats alters the expression of genes related with thyroid hormone regulation

AU - Kim, Minjeong

AU - Jeong, Ji Seong

AU - Kim, Hyunji

AU - Hwang, Seungwoo

AU - Park, Il Hyun

AU - Lee, Byung Chul

AU - Yoon, Sung Il

AU - Jee, Sun Ha

AU - Nam, KiTaek

AU - Lim, Kyung Min

PY - 2018/9/1

Y1 - 2018/9/1

N2 - 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.

AB - 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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