Effects of Ethane Dimethane Sulfonate on the Functional Structure of the Adult Rat Testis

Ariyaratne, S.; Kim, I.; Mills, Nathaniel; Mason, Ian; Mendis-Handagama, Chamindrani

doi:10.1080/713828166

Cited by 5 publications

(12 citation statements)

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“…This is confirmed by our current study which shows that levels of testosterone and most Leydig cell mRNA markers began to recover by 8 days after EDS treatment. This contrasts with normal rats in which testosterone levels begin to recover between 14 and 21 days after EDS (Molenaar et al 1986, Edwards et al 1988b, Sharpe et al 1990, Ariyaratne et al 2003. It is known that germ cell depletion affects Sertoli cell function (McKinnell & Sharpe 1997, Guitton et al 2000, O'Shaughnessy et al 2008 and so the accelerated re-generation of active Leydig cells in germ cell-depleted testes may be due to altered Sertoli cell activity.…”

Section: Discussionmentioning

confidence: 40%

“…Leydig cell re-generation after EDS evidence suggests that Leydig cell re-population of the adult testis following EDS treatment is very similar to the normal developmental process (Teerds 1996, Ariyaratne et al 2003 and it is likely that the same stem cells act as precursors of re-populating Leydig cells. The EDS model offers, therefore, a convenient method for the study of Leydig cell development while use of germ cell-free animals, as described here, allows this to be done on a relatively stable background with no other on-going, age-related, developmental events and without the massive degeneration and re-population of the germ cells which normally occurs following EDS.…”

Section: Discussionmentioning

confidence: 99%

“…In the adult animal, a single injection of EDS leads to rapid ablation of the existing adult Leydig cells followed by Leydig cell repopulation in a manner that appears to recapitulate the normal developmental process (Teerds 1996, Ariyaratne et al 2003. This model, therefore, offers the possibility for studying Leydig cell differentiation in a relatively stable environment without the other ongoing background developmental processes that occur naturally as the animal grows through puberty.…”

Section: Introductionmentioning

confidence: 99%

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Leydig cell re-generation and expression of cell signaling molecules in the germ cell-free testis

O’Shaughnessy

Morris²,

Baker³

2008

Reproduction

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Leydig cells in the rat testis can be specifically ablated with ethane dimethane sulfonate (EDS) and will subsequently re-generate. In this study, we have characterized Leydig cell re-generation and expression of selected cell-signaling molecules in a germ cell-free model of EDS action. This model offers the advantage that re-generation occurs on a stable background without confounding changes from the regressing and repopulating germ cell population. Adult rats were treated with busulfan to remove the germ cell population and Leydig cells were then ablated with EDS. Testicular testosterone levels declined markedly within 24 h of EDS treatment and started to recover after 8 days. After EDS treatment there were marked declines in levels of Leydig cell-specific mRNA transcripts coding for steroidogenic enzymes cytochrome P450 11a1 (Cyp11a1), cytochrome P450 17a1 (Cyp17a1), 3b-hydroxysteroid dehydrogenase type 1 (Hsd3b1), 17b-hydroxysteroid dehydrogenase type 3 (Hsd17b3) and the LH receptor. Levels of all transcripts recovered within 20 days of EDS treatment apart from Hsd17b3, which remained undetectable up to 20 days. Immunohistochemical localization of CYP11A1 during the phase of early Leydig cell re-generation showed that the Leydig cell precursors are spindle-shaped peritubular cells. Studies on factors which may be involved in Leydig cell re-generation showed there were significant but transient increases in platelet-derived growth factor A (Pdgfa), leukemia inhibitory factor (Lif ), and neurofilament heavy polypeptide (Nefh) after EDS, while desert hedgehog (Dhh) levels declined sharply but recovered by 3 days. This study shows that the Leydig cell precursors are peritubular cells and that expression of Pdgfa and Lif is increased at the start of the re-generation process when precursor proliferation is likely to be taking place. Reproduction (2008) 135 851-858

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Section: Discussionmentioning

confidence: 40%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Leydig cell re-generation and expression of cell signaling molecules in the germ cell-free testis

O’Shaughnessy

Morris²,

Baker³

2008

Reproduction

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“…EDS purity was checked using a Bruker DPX-400, 400 MHz High Performance Digital FT-NMR nuclear magnetic resonance spectrometer (Bruker BioSpin GmbH, Rheinstetten, Germany) and was found to be over 99%. The rats received a single intraperitoneal injection of EDS at the dose of 75 mg/kg bodyweight, based on a previous report [4].…”

Section: Eds Treatmentmentioning

confidence: 99%

“…EDS is not commercially available but can be synthesized according to the method used by Jackson and Jackson [2]. Several studies have shown that EDS specifically and temporarily destroys Leydig cells during the first week of its administration in the adult testes, reduces serum testosterone levels, elevates pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), impairs spermatogenesis , and causes severe morphologic alterations of the testicular germinal and interstitial compartments [3,4]. All these occur after only a single dose of EDS injection.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of vitamin E on ethane dimethane sulfonate-induced testicular toxicity in rats

Şahıntürk¹,

Guclu²,

Bayçu³

2007

Asian J Andrology

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Stem Leydig cells: From fetal to aged animals

Chen¹,

Stanley²,

Jin³

et al. 2010

Birth Defects Research Pt C

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Leydig cells are the testosterone-producing cells of the testis. The adult Leydig cell (ALC) population ultimately develops from undifferentiated mesenchymal-like stem cells present in the interstitial compartment of the neonatal testis. Distinct stages of ALC development have been identified and characterized. These include stem Leydig cells (SLCs), progenitor Leydig cells, immature Leydig cells, and ALCs. This review describes our current understanding of the SLCs in the fetal, prenatal, peripubertal, adult, and aged rat testis, as well as recent studies of the differentiation of steroidogenic cells from the stem cells of other organs.

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Effects of Ethane Dimethane Sulfonate on the Functional Structure of the Adult Rat Testis

Cited by 5 publications

References 0 publications

Leydig cell re-generation and expression of cell signaling molecules in the germ cell-free testis

Leydig cell re-generation and expression of cell signaling molecules in the germ cell-free testis

Protective effects of vitamin E on ethane dimethane sulfonate-induced testicular toxicity in rats

Stem Leydig cells: From fetal to aged animals

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