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Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in
Jianhai Zhang1, Yufang Zhang2, Chen Liang1
1Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, China.
Abstract:
Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150mg/L NaF in drinking water, 5.75g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration.
Insights
Choline supplementation may protect male reproductive health from fluoride toxicity. This study found choline improved sperm health and testicular function in mice exposed to sodium fluoride (NaF).
Area of Science:
- Reproductive Toxicology
- Environmental Health
- Nutritional Science
Background:
- Fluoride exposure is a known cause of male reproductive toxicity.
- The mechanisms underlying fluoride's effects on male reproduction require further investigation.
- Choline, an essential nutrient, has potential but understudied roles in male reproductive health.
Purpose of the Study:
- To investigate the protective effects of choline against sodium fluoride (NaF)-induced male reproductive toxicity.
- To explore the involvement of the MAPK pathway in choline's protective mechanism.
Main Methods:
- Male mice were exposed to sodium fluoride (NaF) in drinking water and supplemented with choline in their diet from gestation to 15 weeks post-birth.
- Evaluated parameters included body weight, sperm count and viability, testicular histology, and gene/protein expression (NGF, Ras, Raf, MEK).
Main Results:
- Fluoride exposure reduced body weight, sperm count, and sperm survival, and altered testicular histology.
- Fluoride exposure down-regulated mRNA expression of NGF, Ras, Raf, and MEK, and decreased NGF and phosphor-MEK protein levels in testes.
- Choline supplementation ameliorated fluoride-induced reductions in body weight, sperm parameters, and testicular damage.
Conclusions:
- Choline supplementation alleviates fluoride-induced testicular toxicity in male mice.
- The protective effect of choline appears to be mediated by restoring NGF and phosphor-MEK expression via the MAPK pathway.
- Further research is needed to determine optimal choline dosage and supplementation duration.
