Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences, Kawasaki, Japan.
Department of Hygiene Chemistry, School of Pharmaceutical Sciences, Ohu University, Koriyama, Japan.
Andrology. 2021 Sep;9(5):1579-1592. doi: 10.1111/andr.13013. Epub 2021 Jun 29.
The increasing availability of fortified foods and supplements has caused an overconsumption of vitamin A (VA), above the recommended level. To date, the effects of chronic VA excess (VAE) on spermatogenesis remain unclear.
This study aims to investigate the long-term excessive intake of VA effects on spermatogenesis in mice.
Dams were initially fed a control diet (4 IU/g) or a VAE diet (250 IU/g), 4 weeks prior to mating and during pregnancy. Dams and their male pups continued this diet regimen until the offspring reached 12 weeks of age. At 12 weeks of age, epididymis caudal spermatozoa and testes were collected. For histological analysis, sections were stained with periodic acid-Schiff-hematoxylin, and quantitative PCR was used to detect changes in gene expression in the testes of the VAE mice. Sperm motility and morphology were evaluated to detect the endpoint of VAE toxicity.
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 was able to influence both pre- and post-meiotic spermatogenesis. As a result of testicular toxicity, we demonstrated, to the best of our knowledge, for the first time that long-term VAE caused sperm-head abnormalities.
强化食品和补充剂的日益普及导致维生素 A(VA)的摄入量超过了建议水平,出现了 VA 摄入过量的情况。迄今为止,慢性 VA 摄入过量(VAE)对精子发生的影响仍不清楚。
本研究旨在探讨长期过量摄入 VA 对小鼠精子发生的影响。
在交配前 4 周和妊娠期间,母鼠最初喂食对照饮食(4 IU/g)或 VAE 饮食(250 IU/g)。母鼠及其雄性幼崽在 12 周龄前继续这种饮食方案。在 12 周龄时,收集附睾尾部精子和睾丸。进行组织学分析时,用过碘酸-希夫-苏木精染色切片,并用定量 PCR 检测 VAE 小鼠睾丸中基因表达的变化。评估精子活力和形态,以检测 VAE 毒性的终点。
对照组和 VAE 组的体重无显著差异。对照组和 VAE 组的睾丸横切片均包含正常排列的生殖细胞,两组的每日精子产量相似。然而,VAE 组的 VII 期和 VIII 期生精小管的比例明显低于对照组。此外,在 VAE 组的睾丸中,与视黄醇代谢、精子发生和精子形成相关的基因表达发生了显著变化。同样,VAE 组的精子活力和头部形态明显受损。
我们的研究结果表明,长期饮食摄入 VAE 能够影响减数分裂前和减数分裂后的精子发生。由于睾丸毒性,我们首次证明,长期 VAE 导致精子头部异常。