Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, PR China.
College of Biology, Department of Molecular Medicine, Hunan University, Changsha, 410082, PR China.
Environ Pollut. 2019 Oct;253:538-551. doi: 10.1016/j.envpol.2019.06.107. Epub 2019 Jul 5.
The effect of fluoride as an ongoing topic has attracted much attentions due to the decline in overall human fertility worldwide. However, whether fluorine causes a temporary stimulus or permanent damage to the male reproductive system, as well as the mechanism of fluoride influencing spermatogenesis remained unclear. 48 adult male rats were randomly divided into four groups (twelve each). Control group received the distilled water, while the other three groups were treated with 25, 50, 100 mg/L NaF via drinking water for 8 weeks. Six rats from each group were selected randomly to detect the levels of various indices related to spermatogenesis. The remaining rats were given only distilled water and left for recovery of a period of 2 weeks. Results showed that the levels of serum CK, ALP, CHE, BUN, UA, and Cr, testis morphology and the ultrastructure of sperm acrosome and chromatoid body (CB) were significantly changed by fluoride. Interestingly, the elongated spermatid counts, spermatids elongation ratio, and mRNA expressions of Prm1/2 and MIWI, TDRD1, TDRD 6, TDRD7, PABP, and Hsp72 related to CB decreased markedly in fluoride treatment groups compared to the control. Furthermore, the expression levels of DDX25 and associated regulatory proteins like CRM1, HMG2, H4, TP2, and PGK2 were down-regulated by fluoride. After 2-weeks withdrawal period, out of the 19 altered spermatogenesis indicators, 15 indicators in 100 mg/L group and 3 indicators in 50 mg/L group still exhibited a significant change, while none showed change in 25 mg/L group. These results proved that the reversibility of fluoride toxicity is dose-dependent on the male reproductive system. Meanwhile, fluoride caused unrestored arrest during the haploid period of spermatogenesis, where reduced DDX25 and associated regulatory proteins play a crucial role in this process, which could provide the underlying insights to the toxic mechanism of fluoride induced male reproductive toxicity.
氟化物作为一个持续的话题，由于全球人类总生育率的下降，引起了广泛关注。然而，氟是否对男性生殖系统造成暂时的刺激或永久性损伤，以及氟影响精子发生的机制尚不清楚。48 只成年雄性大鼠随机分为四组（每组 12 只）。对照组给予蒸馏水，其余三组分别给予 25、50、100mg/L 的 NaF 通过饮用水处理 8 周。每组随机选择 6 只大鼠检测与精子发生相关的各种指标水平。其余大鼠仅给予蒸馏水，恢复 2 周。结果表明，氟化物显著改变了血清 CK、ALP、CHE、BUN、UA、Cr、睾丸形态和精子顶体及染色质体（CB）的超微结构。有趣的是，与对照组相比，氟化物处理组的伸长精子计数、精子伸长率、以及与 CB 相关的 Prm1/2 和 MIWI、TDRD1、TDRD6、TDRD7、PABP 和 Hsp72 的 mRNA 表达显著降低。此外，氟化物下调了 DDX25 及其相关调节蛋白如 CRM1、HMG2、H4、TP2 和 PGK2 的表达水平。经过 2 周的停药期后，在 19 个改变的精子发生指标中，100mg/L 组的 15 个指标和 50mg/L 组的 3 个指标仍显示出显著变化，而 25mg/L 组则没有变化。这些结果证明，氟化物对雄性生殖系统的毒性逆转与剂量有关。同时，氟化物导致精子发生的单倍体时期出现不可逆转的阻滞，其中减少的 DDX25 和相关调节蛋白在这个过程中发挥关键作用，这为氟化物引起雄性生殖毒性的毒性机制提供了潜在的见解。
