Host: The Japanese Society of Toxicology
Epidemiological studies have suggested that more than 75% of individuals in the developed countries routinely ingest more than the recommended dietary allowance for vitamin A (VA), most of it from fortified foods and supplements. The current recommended daily allowance of VA in adults is 3000 IU/day in males while the upper tolerable limit is 10,000 IU/day. Although it has been reported that long-term VA deficiency (VAD) results in spermatogenic arrest at the early stage of spermatogenesis, the effects of VA excess (VAE) on spermatogenesis have not been well investigated. The present study was designed to determine the effects of chronic VAE on mouse spermatogenesis and to explore potential molecular toxicological mechanisms of VAE. The VA content of 250 IU/g in the diet used in this study is 3.75 times the upper tolerable limit for VA. As a result, body weights were not significantly different between the control and VAE groups. Testicular cross-sections from the control and VAE mice contained a normal array of germ cells, and the daily sperm production was similar between the two groups. However, the percentage of seminiferous tubules in stages VII and VIII was significantly lower in the VAE mice than in the control. In addition, significant changes in the expression of genes involved in retinoid metabolism, spermatogenesis, and spermiogenesis were detected in the testes of the VAE mice. Consistently, sperm motility and head morphology were significantly impaired in the VAE mice. Our findings suggest that long-term dietary intake of VAE were able to influence both pre- and post-meiotic spermatogenesis.
