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Published on: March 29, 2018
Developmental fluoride exposure influenced rat's splenic development and cell cycle via disruption of the ERK signal
Yanqin Ma1, Kankan Zhang2, Fengjun Ren2
1College of Life Science, Shanxi Agricultural University, Taigu, Shanxi 030801, China; Shanxi Key Laboratory of Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, China.
Insights
High fluoride intake during development impairs spleen growth and function in rats. This study reveals fluoride disrupts lymphocyte proliferation and the MAPK/ERK pathway, crucial for spleen development.
Area of Science:
- Toxicology
- Developmental Biology
- Immunology
Background:
- Excessive fluoride exposure can harm the spleen.
- The neonatal period is critical for spleen and lymphocyte development.
- Children may be more susceptible to fluoride toxicity.
Purpose of the Study:
- To investigate the effects of postnatal fluoride exposure on spleen development.
- To identify the underlying signaling pathways affected by fluoride.
Main Methods:
- Rats were exposed to fluoride from the neonatal period to early adulthood.
- Spleen weight, morphology, splenocyte cell cycle, and mRNA expression of IL-2 were analyzed.
- The MAPK/ERK pathway (Raf-1/MEK-1/ERK-2/c-fos, ERK/p-ERK) was examined.
Main Results:
- Fluoride exposure reduced spleen weight index and altered spleen morphology.
- Cell cycle arrest in splenocytes and decreased IL-2 mRNA expression were observed.
- Fluoride exposure inhibited ERK phosphorylation and altered MAPK/ERK pathway gene expression.
Conclusions:
- Postnatal fluoride exposure adversely impacts spleen development and lymphocyte proliferation.
- The MAPK/ERK pathway plays a critical role in fluoride-induced spleen development interference.
Abstract:
Excessive fluoride exposure has been reported to cause damage to spleen. Neonatal period is characterized by rapid proliferation and differentiation of lymphocyte in the spleen. Children may be more sensitive to the toxicity of fluoride compared to the adults. The aim of this study was to investigate the effects of postnatal exposure (from neonatal period to early adulthood) to fluoride on the development of spleen on a regular basis and the underlying signal pathway. Results showed a marked decrease in spleen weight index and altered morphology in the spleen of fluoride-treated group on PND-84, which reflected fluoride inhibition of the development of spleen. Fluoride exposure induced cell cycle arrest of splenocytes and decreased the mRNA expression of IL-2, which indicated compromised baseline lymphocyte proliferation in the spleen. Time course research from 3-wk-of-age until 12-wk-of-age showed an adverse and cumulative impact of fluoride on the development of spleen. In view of the key role of MAPK/ERK pathway in lymphocyte development, Raf-1/MEK-1/ERK-2/c-fos mRNA expression and ERK/p-ERK protein expression were detected. Results showed despite a transitory increase in mRNA expression from PND-42 to PND-63 in fluoride-treated group, the expression of these genes on PND-84 decreased significantly compared with PND-42 or PND-63. NaF significantly inhibited the phosphorylation of ERK protein on PND-84. Taken together, these results emphasized the vital role of ERK pathway in the interfered development of spleen induced by a high dose of fluoride exposure in rats.
