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. 2012 Apr;126(2):545-53.
doi: 10.1093/toxsci/kfs021. Epub 2012 Jan 23.

Differences in Radiation Sensitivity of Recovery of Spermatogenesis Between Rat Strains

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Free PMC article

Differences in Radiation Sensitivity of Recovery of Spermatogenesis Between Rat Strains

Mahmoud Abuelhija et al. Toxicol Sci. .
Free PMC article

Abstract

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.

Figures

FIG. 1.
FIG. 1.
Weights of testis parenchymal tissue and interstitial fluid for rats of seven different strains 10 weeks after irradiation with 5 Gy. (A) Absolute testis weights. (B) Testis weights relative to unirradiated controls of same strain. (C) Absolute testis interstitial fluid weights. (D) Increase in interstitial fluid weights from unirradiated control levels. In (B) and (D), the values for groups of irradiated rats with different letters (a, b, and c) are significantly different from each other (p < 0.05) and groups with the same letter are not. In (D), * is used to indicate strains that showed significant increases (p < 0.05) in testicular interstitial fluid resulting from irradiation.
FIG. 2.
FIG. 2.
Histology of rat testes 10 weeks after irradiation with 5 Gy. (A) BN testis showing atrophic tubules and interstitial edema. (B) The tubules in BN contained mostly Sertoli cells (SC) but some contained a few type A spermatogonia (Spg). (C) SHR testis showing recovery of spermatogenesis in nearly all tubules. Some tubules in SHR testes (*) showed complete spermatogenesis; other tubules (X) only showed development to the early spermatid stage. (D) Higher magnification image of tubule from irradiated SHR rat showing development to only the early spermatid stage. (Bg) Type B spermatogonia, (P) pachytene spermatocyte, and (RS) round spermatid. Scale (A, C) bar: 100 μm, Scale (B, D) bar: 10 μm.
FIG. 3.
FIG. 3.
Recovery of spermatogenesis as measured by the percentage of tubules with morphologically differentiated cells at a specific stage of differentiation or beyond for different strains of rats. (A) TDI defined as differentiation to the B spermatogonial stage or beyond, unless otherwise noted. (B) Percentage of tubules reaching differentiation to specific stages or beyond. The values for groups of irradiated rats with different letters (a, b, and c) are significantly different from each other (p < 0.05) and groups with the same letter are not.
FIG. 4.
FIG. 4.
Testicular sperm production. (A) Numbers of sonication-resistant late spermatids per testis in rats at 10 weeks after irradiation with 5 Gy. (B) Numbers of sonication-resistant late spermatids relative to unirradiated controls of same strain. The values for groups of irradiated rats with different letters (a, b, c, d, and e) are significantly different from each other (p < 0.05) and groups with the same letter are not.
FIG. 5.
FIG. 5.
Testosterone, LH, and FSH levels in BN and SHR rats at 10 week after irradiation with 5 Gy. (A) Serum testosterone. (B) Intratesticular fluid testosterone. (C) Serum LH. (D) Serum FSH. * Indicates values in SHR are significantly different from those in BN, and † indicates value in irradiated is significantly different from that in unirradiated testes (p < 0.05, t-test).
FIG. 6.
FIG. 6.
Radiation-induced increase in testicular interstitial fluid plotted against the recovery of spermatogenesis at 10 weeks after 5 Gy of irradiation. A linear regression was performed on the data points and the correlation was weak (r2 = 0.25) and not statistically significant (p = 0.25).

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