Differences in Radiation Sensitivity of Recovery of Spermatogenesis Between Rat Strains

Abuelhija, Mahmoud; Weng, Connie C.; Shetty, Gunapala; Meistrich, Marvin L.

doi:10.1093/toxsci/kfs021

Cited by 23 publications

(19 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As shown previously (Abuelhija et al , 2012), there were large increases (~0.2 g) in testicular interstitial fluid in BN rats at 5 Gy of irradiation but small or negligible increases in SHR and SD rats. In all strains, the increases in interstitial fluid were dose-responsive (Fig.…”

Section: Resultssupporting

confidence: 87%

“…The present study clarifies the question of whether the data of our previous study (Abuelhija et al , 2012), showing that at 10 weeks after 5-Gy irradiation there was no recovery of spermatogenesis in BN rats, whereas in SHR and SD rats nearly all of the tubules contained differentiating germ cells, are a result of qualitative or quantitative differences between the strains. The dose-response studies showed that at 10 weeks after irradiation, BN rats failed to show recovery even after low doses (4 Gy) (Fig.…”

Section: Discussionsupporting

confidence: 78%

“…The field extended distally from a line about 6 cm above the base of the scrotum. Different doses (2.7 Gy to 12.5 Gy) were given at a dose rate of approximately 1 Gy/min; dose ranges were chosen for each strain based on the sensitivity observed previously (Abuelhija et al , 2012). Testis tissue was harvested at various times between 10 and 40 weeks after irradiation (Table 1).…”

Section: Methodsmentioning

confidence: 99%

“…Interstitial tubule fluid was collected from the left testis as we had done previously (Abuelhija et al , 2012) using a modification of methods described earlier (Porter et al , 2006; Rhenberg, 1993). Briefly, the testis was suspended by silk sutures and centrifuged for 30 min at 60 × g at 4°C, and the weight of the fluid collected was determined.…”

Section: Methodsmentioning

confidence: 99%

“…To systematically characterize these strain differences, we directly compared the recovery of spermatogenesis at 10 weeks after 5-Gy irradiation in seven rat strains and observed dramatic differences (Abuelhija et al , 2012). There was no recovery of differentiating germ cells in the Lewis and Brown Norway (BN) stains despite the presence of type A spermatogonia in many tubules.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Rat models of post‐irradiation recovery of spermatogenesis: interstrain differences

et al. 2012

Self Cite

View full text Add to dashboard Cite

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 (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.

show abstract

Section: Resultssupporting

confidence: 87%

Section: Discussionsupporting

confidence: 78%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Rat models of post‐irradiation recovery of spermatogenesis: interstrain differences

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

Preservation of chromosomal integrity in murine spermatozoa derived from gonocytes and spermatogonial stem cells surviving prenatal and postnatal exposure to γ‐rays in mice

Watanabe

Kohda

Komura

et al. 2017

Molecular Reproduction Devel

View full text Add to dashboard Cite

Prenatal and postnatal male mice were acutely (659−690 mGy/min) and continuously (0.303 mGy/min) exposed to 2 Gy γ-rays to evaluate spermatogenetic potential and chromosome damage in germ cells at adulthood. Acute irradiation on days 15.5, 16.5, and 17.5 post-coitus (pc) affected testicular development as the result of massive quiescent gonocyte loss. In these testes, the majority of the seminiferous tubules were devoid of germ cells. Acute irradiation on days 18.5 and 19.5 pc had less effect on testicular development and spermatogenesis, even though germ cells on these days were quiescent gonocytes. Adverse effects on testicular development and spermatogenesis were observed following continuous irradiation between 14.5 and 19.5 days pc. Upon exposure to acute and continuous postnatal irradiation after the differentiation of spermatogonial stem cells and spermatogonia, nearly all of the seminiferous tubules were engaged in spermatogenesis. Neither acute nor continuous irradiation directed at quiescent gonocytes was responsible for the increased number of multivalent chromosomes in descendent primary spermatocytes. In contrast, a significant increase in cells with multivalent chromosomes was observed following acute irradiation on days 4 and 11 post-partum (pp). However, there were no significant increases in unstable structural chromosomal aberrations and aneuploidy in spermatozoa, regardless of cell stage at irradiation or the radiation dose-rate. Thus, germ cells surviving prenatal and postnatal irradiation can restore spermatogenesis and produce viable spermatozoa without chromosome damage. These findings may provide a better understanding of reproductive potential following accidental, environmental, or therapeutic irradiation during the prenatal and postnatal periods in humans.

show abstract

Functional role of GKAP1 in the regulation of male germ cell spontaneous apoptosis and sperm number

Wang

Wang²,

Dai

et al. 2019

Molecular Reproduction Devel

View full text Add to dashboard Cite

G kinase‐anchoring protein 1 (GKAP1) is a G kinase‐associated protein that is conserved in many eutherians and is mainly expressed in the testis, especially in spermatocytes and round spermatids. The function of GKAP1 in the testis is largely unknown. Here, we revealed that deletion of GKAP1 led to an increase in sperm production with swollen epididymis, and germ cell apoptosis was found to decrease in GKAP1 knock‐out mice. Further investigations showed that a deficiency of GKAP1 could partly change the cellular location of cGK‐Iα and increase the amount of active cAMP response element‐binding protein (CREB) in the nucleus. Therefore, the expression of a particular inhibitor of apoptosis proteins (IAPs) was upregulated because of the activation of CREB, and this increase in IAPs was associated with a decrease in the level of activated caspase‐3. These results suggest that a deficiency of GKAP1 in mouse testis could increase sperm production through a reduction of the spontaneous apoptosis of germ cells in the testis, possibly because of a change in the activity of the cGK‐Iα pathway.

show abstract

Differences in Radiation Sensitivity of Recovery of Spermatogenesis Between Rat Strains

Cited by 23 publications

References 38 publications

Rat models of post‐irradiation recovery of spermatogenesis: interstrain differences

Rat models of post‐irradiation recovery of spermatogenesis: interstrain differences

Preservation of chromosomal integrity in murine spermatozoa derived from gonocytes and spermatogonial stem cells surviving prenatal and postnatal exposure to γ‐rays in mice

Functional role of GKAP1 in the regulation of male germ cell spontaneous apoptosis and sperm number

Contact Info

Product

Resources

About