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. 2013 Mar;1(2):206-15.
doi: 10.1111/j.2047-2927.2012.00034.x. Epub 2012 Nov 29.

Rat Models of Post-Irradiation Recovery of Spermatogenesis: Interstrain Differences

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Rat Models of Post-Irradiation Recovery of Spermatogenesis: Interstrain Differences

M Abuelhija et al. Andrology. .
Free PMC article

Abstract

Recently, we reported large differences between rat strains in spermatogenesis recovery at 10 weeks after 5-Gy irradiation suggesting that there are interstrain as well as interspecies differences in testicular radiation response. To determine whether these interstrain differences in sensitivity might be a result of the particular dose and time-point chosen, we performed dose-response and time-course studies on sensitive Brown-Norway (BN) and more resistant spontaneously hypertensive rats (SHR) and Sprague-Dawley (SD) rats. Type A spermatogonia were observed in atrophic tubules at 10 weeks after irradiation in all strains indicating that tubular atrophy was caused by a block in their differentiation, but the doses to produce the block ranged from 4.0 Gy in BN to 10 Gy in SD rats. Although the numbers of type A spermatogonial were unaffected at doses below 6 Gy, higher doses reduced their number, indicating that stem cell killing also contributed to the failure of recovery. After 10 weeks, there was no further recovery and even a decline in spermatogonial differentiation in BN rats, but in SHR rats, sperm production returned to control levels by 20 weeks after 5.0 Gy and, after 7.5 Gy, differentiation resumed in 60% of tubules by 30 weeks. Suppression of testosterone and gonadotropins after irradiation restored production of differentiated cells in nearly all tubules in BN rats and in all tubules in SHR rats. Thus, the differences in recovery of spermatogenesis between strains were a result of both quantitative differences in their sensitivities to a radiation-induced, hormone-dependent block of spermatogonial differentiation and qualitative interstrain differences in the progression of post-irradiation recovery. The progression of recovery in SHR rats was similar to the prolonged delays in recovery of human spermatogenesis after cytotoxic agent exposure and thus may be a system for investigating a phenomenon also observed in men.

Conflict of interest statement

DISCLOSURES

The authors have no conflicting financial interests.

Figures

FIG 1
FIG 1
Weights of testis parenchymal tissue and interstitial fluid of BN, SHR and SD rats 10 weeks after irradiation. (A) Testis weights relative to those of unirradiated controls of same strain. Control values were 1.50 g, 1.27 g, and 1.66 g for BN, SHR, and SD, respectively. (B) Increase in interstitial fluid weights from unirradiated control levels.
FIG 2
FIG 2
Recovery of spermatogenesis at 10 weeks after various doses of radiation. (A) Tubule differentiation index (TDI), defined as percentage of tubules differentiating to the B spermatogonial stage or beyond. (B) Testicular sperm production: numbers of sonication-resistant late spermatids per testis. The dashed lines indicate the control values.
FIG 3
FIG 3
Numbers of type A spermatogonia per 100 Sertoli cells in nonrepopulating tubules of (A) BN, SHR, and SD rats 10 weeks after irradiation (dose-response), and (B) BN and SHR rats at longer periods of time after different doses of irradiation (time course).
FIG 4
FIG 4
Time courses of changes in (A,B) absolute testis weights, (C,D) tubule differentiation indices, and (E,F) sperm head counts of BN (A,C,E) and SHR (B,D,F) rats after different doses of radiation. The dashed lines indicate the control values. (*) indicates significantly different from value at 10 weeks (P<0.05, t-test).
FIG 5
FIG 5
Recovery of progression of spermatogenesis as measured by the percentage of tubules with morphologically differentiated cells reaching indicated stage of differentiation or beyond for SHR rats at various times after (A) 6.5 Gy or (B) 7.5 Gy.
FIG 6
FIG 6
Hormones levels in BN, SHR, and SD rats measured 10 weeks after different doses of radiation. (A) Serum testosterone. (B) Intratesticular fluid testosterone. (C) Serum FSH. (*) indicates values in SHR are significantly different from those in BN. (#) indicates values in SHR are significantly different from those in SD. ($) indicates values in SD are significantly different from those in BN (P<0.05, t-test).
FIG 7
FIG 7
Hormone levels in BN and SHR rats without hormone suppression (filled symbols) and after hormone suppression (open symbols) at different times after 7.5 Gy irradiation. (A) Serum testosterone. (B) Intratesticular fluid testosterone. (C) Serum FSH. LOD indicates limit of detection of the assay, (L) Indicates undetectable values of some but not all samples in the group.
FIG 8
FIG 8
Dose-response and time-course of changes in testis weights, differentiation in tubules, and interstitial fluid in BN and SHR rats without hormone suppression (filled symbols) and after hormone suppression (open symbols). (A,D) Testis weights relative to unirradiated controls of same strain. (B,E) Percentage of tubules with differentiated cells. (C,F) Change in interstitial fluid weights from unirradiated control levels.
FIG 9
FIG 9
Histology of BN rat testes 10 weeks after irradiation with 7.5 Gy without (A,B) or with (C,D) hormone suppression. (A) Irradiation produced atrophic tubules and interstitial edema. (B) Most tubules contained only Sertoli cells (SC) but some contained a few type A spermatogonia (Spg). (C) Hormone suppression after irradiation induced recovery of spermatogenesis in nearly all tubules, except those marked with. (X). (D) The recovering tubules showed development to only the pachytene spermatocyte stage (p). (A,C) bar: 100 µm, (B,D) bar: 10 µm.

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