Failure of Spermatogenesis to Recover Despite the Presence of A Spermatogonia in the Irradiated LBNF1 Rat1

Kangasniemi, Marko; Huhtaniemi, Ilpo; Meistrich, Marvin L.

doi:10.1095/biolreprod54.6.1200

Cited by 112 publications

(84 citation statements)

References 34 publications

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“…Ischemia was induced by a clockwise 720°torsion applied to the spermatic cord by open surgery (21) for 1 h, followed by a return to the natural position to allow for reperfusion of the tissue. Exposure of testes to ionizing radiation was performed according to published procedures and doses (22,23). Briefly, anesthetized animals were irradiated locally at a distance of 100 cm with a single total dose of 6.5 gray of X-rays produced by a linear accelerator.…”

Section: Methodsmentioning

confidence: 99%

Ceramides and Sphingomyelins with High Proportions of Very Long-chain Polyunsaturated Fatty acids in Mammalian Germ Cells

Furland

Zanetti

Oresti

et al. 2007

Journal of Biological Chemistry

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Very long-chain polyunsaturated fatty acids (VLCPUFA) have previously been shown to be components of sphingomyelin (SM) of mammalian testis and spermatozoa. Here we examined the fatty acids of testicular ceramide (Cer) in comparison with those of SM in some mammals with a special focus on the rat testis. In bull, cat, dog, rabbit, mouse, and rat, VLCPUFA were found in both testicular lipids, Cer having a higher percentage of VLCPUFA than SM. Rat testis had the highest percentage of VLCPUFA in both lipids, the major ones being 28:4n-6 and 30:5n-6. VLCPUFA-containing SM and Cer occurred in cells located in the seminiferous tubules, where germ cells had a higher percentage of these species than Sertoli cells. Seminiferous tubule fractionation showed that SM and Cer of mitochondria and lysosomes had mostly saturates and negligible VLCPUFA, the latter being important in the SM and Cer of microsomes and other membrane fractions. VLCPUFA were absent from the SM and Cer of rat prepuberal testis, increased with the onset of spermatogenesis to account for nearly 15 and 40% of the total fatty acids of testicular SM and Cer, respectively, remained at those levels throughout the adult life of fertile rats and tended to decrease at advanced ages. Four conditions that lead to selective death of germ cells in vivo, namely experimental cryptorchidism, post-ischemic reperfusion, focalized x-ray irradiation and treatments with the antineoplasic drug doxorubicin, caused the VLCPUFA to disappear from the testicular SM and Cer of adult fertile rats, showing that these lipids are specific traits of spermatogenic cells.

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Section: Methodsmentioning

confidence: 99%

Ceramides and Sphingomyelins with High Proportions of Very Long-chain Polyunsaturated Fatty acids in Mammalian Germ Cells

Furland

Zanetti

Oresti

et al. 2007

Journal of Biological Chemistry

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“…Dysfunction of the somatic environment could lead to failure of normal spermatogenesis to proceed. For example, in irradiated rat testes, the surviving spermatogonial stem cells are capable of self-renewal and proliferation, but they are unable to differentiate and instead undergo apoptosis (Kangasniemi et al 1996, Meistrich & Shetty 2003. In an attempt to determine whether the radiation damaged the spermatogonia or the somatic environment, we recently transplanted spermatogonia from immature or irradiated adult green fluorescent protein (GFP)-transgenic rats into irradiated LBNF 1 rats or nude mice respectively.…”

Section: Introductionmentioning

confidence: 99%

Donor Sertoli cells transplanted into irradiated rat testes stimulate partial recovery of endogenous spermatogenesis

et al. 2009

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Irradiation of rat testes leads to the failure to support differentiation of the surviving spermatogonia due to damage of the somatic environment. To determine the involvement of Sertoli cells in this somatic damage, we transplanted seminiferous tubule cells from normal immature GFP-transgenic rats into the testes of irradiated rats. The donor Sertoli cells colonized and developed in the host testes. In many seminiferous tubules, the donor Sertoli cells formed abnormal spherical structures in the lumen, but in some tubules they formed a normal-appearing epithelium, but with only isolated spermatogonia, on the basement membrane. When the donor cells were injected into the interstitial region of the testis, they formed tubule-like structures containing Sertoli cells and occasional isolated spermatogonia, both of donor origin. Surprisingly, in host tubules adjacent to these newly formed donor-cell tubules or adjacent to the endogenous tubules with abnormal donor Sertoli-cell structures, endogenous spermatogonia differentiated to the spermatocyte or even to spermatid stages. Around these newly donor cell-formed tubules and the host tubules with abnormal donor Sertoli-cell structures, many cells including macrophages, which perhaps represented chronic inflammation, accumulated in the interstitium. We conclude that the donor Sertoli cells that colonized the seminiferous tubules did not directly support recovery of spermatogenesis. Instead, the colonizing Sertoli cells acted indirectly on the interstitium to stimulate localized differentiation of endogenous spermatogonia.

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“…The irradiated testis model provides a powerful avenue for investigating the regulation of c-Kit expression spermatogonia, as irradiation destroys the radiosensitive differentiating spermatogonia, leaving the testis populated only by undifferentiated spermatogonia (Kangasniemi et al 1996). Gonadotrophinreleasing hormone (GnRH) antagonists stimulate recovery of spermatogenesis when applied at 15 weeks after irradiation and recovery is assessed by scoring the percentage of tubules containing germ cells that have reached the B spermatogonial stage or later, termed the repopulation index.…”

Section: Introductionmentioning

confidence: 99%

Expression of c-Kit receptor mRNA and protein in the developing, adult and irradiated rodent testis

Prabhu¹,

Meistrich²,

McLaughlin³

et al. 2006

Reproduction

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Germ cell proliferation, migration and survival during all stages of spermatogenesis are affected by stem cell factor signalling through the c-Kit receptor, the expression and function of which are vital for normal male reproductive function. The present study comprehensively describes the c-Kit mRNA and protein cellular expression profiles in germ cells of the postnatal and adult rodent testis, revealing their significant elevation in synthesis at the onset of spermatogenesis. Real-time PCR analysis for both mice and rats matched the cellular mRNA expression profile where examined. Localization studies in normal mouse testes indicated that both c-Kit mRNA and protein are first detectable in differentiating spermatogonia. In addition, all spermatogonia isolated from 8-day-old mice displayed detectable c-Kit mRNA, but 30 -50% of these lacked protein expression. The c-Kit mRNA and protein profile in normal rat testes indicated expression in gonocytes, in addition to differentiating spermatogonia. However, in the irradiated adult rat testes, in which undifferentiated spermatogonia are the only germ cell type, mRNA was also detected in the absence of protein. This persisted at 3 days and 1 and 2 weeks following treatment with gonadotrophin-releasing hormone (GnRH) antagonist to stimulate spermatogenesis recovery. By 4 weeks of GnRH antagonist treatment, accompanying the emergence of differentiating spermatogonia, both mRNA and protein were detected. Based on these observations, we propose that c-Kit mRNA and protein synthesis are regulated separately, possibly by influences linked to testis maturation and circulating hormone levels.

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Failure of Spermatogenesis to Recover Despite the Presence of A Spermatogonia in the Irradiated LBNF1 Rat1

Cited by 112 publications

References 34 publications

Ceramides and Sphingomyelins with High Proportions of Very Long-chain Polyunsaturated Fatty acids in Mammalian Germ Cells

Ceramides and Sphingomyelins with High Proportions of Very Long-chain Polyunsaturated Fatty acids in Mammalian Germ Cells

Donor Sertoli cells transplanted into irradiated rat testes stimulate partial recovery of endogenous spermatogenesis

Expression of c-Kit receptor mRNA and protein in the developing, adult and irradiated rodent testis

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