Morphological and functional deterioration of the rat thyroid following chronic exposure to low-dose PCB118

Tang, Jinmei; Wen, Li; Xie, Yingxin; Guo, Hongwei; Cheng, Pei; Chen, Huanhuan; Zheng, Xuqin; Jiang, Lin; Cui, Dai; Liu, Yun; Ding, Guoxian; Duan, Yu

doi:10.1016/j.etp.2013.02.001

Cited by 23 publications

(19 citation statements)

References 26 publications

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“…The dilated ER and fractured microvilli coincide with Tang's finding [36] in which PCB118, one type of environmental pollutant, could also disrupt the structure of thyroid follicular cells. The ER is a central cellular organelle in which transmembrane and secretory proteins are synthesized, folded, and matured [37] .…”

Section: Discussionmentioning

confidence: 91%

Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats

et al. 2014

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Aim: Excess dietary fat intake can induce lipotoxicity in non-adipose tissues. The aim of this study was to observe the effects of dietary high-fat lard intake on thyroid in rats. Methods: Male Sprague-Dawley rats were fed a high-fat lard diet for 24 weeks, and then the rats were fed a normal control diet (acute dietary modification) or the high-fat lard diet for another 6 weeks. The serum lipid profile, total thyroxine (TT4), free thyroxine (FT4) and thyrotropin (TSH) levels were determined at the 12, 18, 24 and 30 weeks. High-frequency ultrasound scanning of the thyroid glands was performed at the 24 or 30 weeks. After the rats were sacrificed, the thyroid glands were collected for histological and immunohistochemical analyses. Results: The high-fat lard diet significantly increased triglyceride levels in both the serum and thyroid, and decreased serum TT4 and FT4 levels in parallel with elevated serum TSH levels. Ultrasonic imaging revealed enlarged thyroid glands with lowered echotexture and relatively heterogeneous features in the high-fat lard fed rats. The thyroid glands from the high-fat lard fed rats exhibited enlarged follicle cavities and flattened follicular epithelial cells under light microscopy, and dilated endoplasmic reticulum cisternae, twisted nuclei, fewer microvilli and secretory vesicles under transmission electron microscopy. Furthermore, the thyroid glands from the highfat lard fed rats showed markedly low levels of thyroid hormone synthesis-related proteins TTF-1 and NIS. Acute dietary modification by withdrawal of the high-fat lard diet for 6 weeks failed to ameliorate the high-fat lard diet-induced thyroid changes. Conclusion: Dietary high-fat lard intake induces significant thyroid dysfunction and abnormal morphology in rats, which can not be corrected by short-term dietary modification.

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Section: Discussionmentioning

confidence: 91%

Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats

et al. 2014

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“…In a previous study, we demonstrated that persistent exposure to low PCB118 concentrations could severely damage thyroidal structure, dramatically decreasing the concentration of serum thyroid hormones. Furthermore, pivotal gene expression such as NIS and thyroglobulin, which determine the synthesis and secretion of thyroid hormones, was remarkably decreased in Wistar rats [ 6 ]. In the present study, we continued exploring the molecular mechanisms of FRTL-5 dysfunction related to low concentrations of PCB118 exposure in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…It was declared that PCBs could interfere with thyroid hormone synthesis, secretion, transportation, and metabolism. Our early findings suggested that low concentrations of 2,3′,4,4′,5-pentachlorobiphenyl or continuous exposure in animal models to polychlorinated biphenyl 118 (PCB118) induced abnormal thyroid morphology, dramatically decreasing the expression of thyroidal sodium/iodide symporter [NIS or solute carrier family 5, member 5 (SLC5A5)] at the transcriptional level [ 6 ]; however, the underlying mechanism was unknown [ 7 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms of 2, 3′, 4, 4′, 5-Pentachlorobiphenyl-Induced Thyroid Dysfunction in FRTL-5 Cells

et al. 2015

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Polychlorinated biphenyls (PCBs) can severely interfere with multiple animals and human systems. To explore the molecular mechanisms underlying 2, 3′, 4, 4′, 5- pentachlorobiphenyl (PCB118)-induced thyroid dysfunction, Fischer rat thyroid cell line-5(FRTL-5) cells were treated with either different concentrations of PCB118 or dimethyl sulfoxide (DMSO). The effects of PCB118 on FRTL-5 cells viability and apoptosis were assessed by using a Cell Counting Kit-8 assay and apoptosis assays, respectively. Quantitative real-time polymerase chain reaction was used to quantify protein kinase B (Akt), Forkhead box protein O3a (FoxO3a), and sodium/iodide symporter (NIS) mRNA expression levels. Western blotting was used to detect Akt, phospho-Akt (p-Akt), FoxO3a, phospho-FoxO3a (p-FoxO3a), and NIS protein levels. Luciferase reporter gene technology was used to detect the transcriptional activities of FoxO3a and NIS promoters. The effects of the constitutively active Akt (CA-Akt) and dominant-negative Akt (DN-Akt) plasmids on p-Akt, p-FoxO3a, and NIS levels were examined in PCB118-treated FRTL-5 cells. The effects of FoxO3a siRNA on FoxO3a, p-FoxO3a, and NIS protein levels were examined in the PCB118-treated FRTL-5 cells. The effects of pcDNA3 (plsmid vectors designed for high-level stable and transient expression in mammalian host)-FoxO3a on NIS promoter activity were examined in the PCB118-treated FRTL-5 cells. Our results indicated that relatively higher PCB118 concentrations can inhibit cell viability in a concentration- and time-dependent manner. Akt, p-Akt, and p-FoxO3a protein or mRNA levels increased significantly in PCB118-treated groups and NIS protein and mRNA levels decreased considerably compared with the control groups. FoxO3a promoter activity increased significantly, whereas NIS promoter activity decreased. These effects on p-FoxO3a and NIS could be decreased by the DN-Akt plasmid, enhanced by the CA-Akt plasmid, and blocked by FoxO3a siRNA. The overexpressed FoxO3a could reduce NIS promoter activity. Our results suggested that PCB118 induces thyroid cell dysfunction through the Akt/FoxO3a/NIS signaling pathway.

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“…PCB 95 administration also significantly increased DNA fragmentation in the thyroid glands of the neonates during the experimental period. Similarly, treatment with PCBs leads to distinct histopathological changes in the thyroid gland (Tang et al 2013), such as hyperplasia of the follicular epithelium, colloidal content reduction, vascularization, and lymphocyte infiltration in perifollicular areas (Gu et al 2009). Furthermore, there is substantial evidence that perinatal exposure to PCBs and their hydroxylated metabolites decreases the concentrations of THs in the offspring (Crofton et al 2000a,b, Meerts et al 2002, Boas et al 2012.…”

Section: Discussionmentioning

confidence: 99%

Early weaning PCB 95 exposure alters the neonatal endocrine system: thyroid adipokine dysfunction

Ahmed

2013

Journal of Endocrinology

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Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that can severely disrupt the endocrine system. In the present study, early-weaned male rats were administered a single dose of 2,3,6-2 0 ,5 0 -pentachlorinated biphenyl (PCB 95; 32 mg/kg per day, by i.p. injection)for two consecutive days (postnatal days (PNDs) 15 and 16) and killed 24 and 48 h after the administration of the last dose. Compared with the control group, administration of PCB 95 induced a reduction (P!0.01) in serum concentrations of thyroxine, triiodothyronine, and GH and an increase (P!0.01) in the serum concentration of TSH at PNDs 17 and 18. These conspicuous perturbations led to some histopathological deterioration in the thyroid gland characterized by follicular degeneration, edema, fibrosis, hemorrhage, luminal obliteration, and hypertrophy with reduced colloidal contents at PND 18. The dyshormonogenesis and thyroid dysgenesis may be attributed to the elevation of DNA fragmentation at PNDs 17 and 18. Furthermore, this hypothyroid state revealed higher (P!0.01) serum concentrations of leptin, adiponectin, and tumor necrosis factor and lower (P!0.01) serum concentrations of IGF1 and insulin at both PNDs compared with the control group. Interestingly, the body weight of the neonates in the PCB 95 group exhibited severe decreases throughout the experimental period in relation to that of the control group. These results imply that PCB 95 may act as a disruptor of the developmental hypothalamic-pituitary-thyroid axis. Hypothyroidism caused by PCB 95 may impair the adipokine axis, fat metabolism, and in general postnatal development. Thus, further studies need to be carried out to understand this concept. Key Words" PCB 95" thyroid " adipokines " rat newborns

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Morphological and functional deterioration of the rat thyroid following chronic exposure to low-dose PCB118

Cited by 23 publications

References 26 publications

Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats

Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats

Molecular Mechanisms of 2, 3′, 4, 4′, 5-Pentachlorobiphenyl-Induced Thyroid Dysfunction in FRTL-5 Cells

Early weaning PCB 95 exposure alters the neonatal endocrine system: thyroid adipokine dysfunction

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