Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Toxicol Sci. 2012 Apr;126(2):545-53. doi: 10.1093/toxsci/kfs021. Epub 2012 Jan 23.
Previous studies with Lewis/Brown-Norway (BN) F1 hybrid rats indicated that spermatogenesis was much more sensitive to ionizing radiation than in the widely studied outbred Sprague Dawley stock, suggesting that there were genetically based differences; however, the relative sensitivities of various inbred strains had not been established. As a first step to defining the genes responsible for these differences, we compared the sensitivities of seven rat strains to radiation damage of spermatogenesis. Recovery of spermatogenesis was examined 10 weeks after 5-Gy irradiation of seven strains (BN, Lewis, Long-Evans, Wistar Kyoto, spontaneously hypertensive [SHR], Fischer 344, and Sprague Dawley). The percentages of tubules containing differentiated cells and testicular sperm counts showed that BN and Lewis were most sensitive to radiation (< 2% of tubules recovered, < 2 × 10(5) late spermatids per testis), Long-Evans, Wistar Kyoto, Fischer, and SHR were more resistant, and Sprague Dawley was the most resistant (98% of tubules recovered, 2 × 10(7) late spermatids per testis). Although increases in intratesticular testosterone levels and interstitial fluid volume after irradiation had been suggested as factors inhibiting recovery of spermatogenesis, neither appeared to correlate with the radiation sensitivity of spermatogenesis in these strains. In all strains, the atrophic tubules without differentiated germ cells nevertheless showed the presence of type A spermatogonia, indicating that their differentiation was blocked. Thus, we conclude that the differences in radiation sensitivity of recovery of spermatogenesis between rat strains of different genetic backgrounds can be accounted for by differences in the extent of the radiation-induced block of spermatogonial differentiation.
先前的研究表明，与广泛研究的远交 Sprague Dawley 品系相比，Lewis/Brown-Norway (BN) F1 杂种大鼠的精子发生对电离辐射更为敏感，这表明存在遗传基础差异；然而，各种近交系的相对敏感性尚未确定。作为定义这些差异相关基因的第一步，我们比较了 7 种大鼠品系对精子发生辐射损伤的敏感性。在 5Gy 照射后 10 周，观察 7 个品系（BN、Lewis、Long-Evans、Wistar Kyoto、自发性高血压 [SHR]、Fischer 344 和 Sprague Dawley）的精子发生恢复情况。分化细胞的小管百分比和睾丸精子计数显示，BN 和 Lewis 对辐射最敏感（<2%的小管恢复，<2×10^5 个睾丸晚期精子），Long-Evans、Wistar Kyoto、Fischer 和 SHR 更具抗性，而 Sprague Dawley 最具抗性（98%的小管恢复，2×10^7 个睾丸晚期精子）。尽管有人提出，照射后睾丸内睾酮水平和间质液体积的增加可能是抑制精子发生恢复的因素，但这两者似乎都与这些品系中精子发生的辐射敏感性无关。在所有品系中，没有分化生殖细胞的萎缩小管仍然存在 A 型精原细胞，表明它们的分化受阻。因此，我们得出结论，不同遗传背景的大鼠品系之间精子发生恢复的辐射敏感性差异可以用精原细胞分化的辐射诱导阻断程度的差异来解释。
