Analysis Tools
reproductive system
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• males show progressive loss of germ cells in the seminiferous tubules from 4 weeks, with complete loss of germ cells by 8 weeks of age
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• adult males show a 67% reduction in epididymal sperm count relative to control males
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• at 8 weeks of age, germ cell proliferation is significantly reduced in the seminiferous epithelium, as shown by Ki-67 immunostaining
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• at 8 weeks of age, excessive germ cell apoptosis is detected by a TUNEL assay
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• impaired cytoskeletal organization and cell polarity of Sertoli cells results in disruption of cell architecture throughout the seminiferous epithelium
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• immunofluorescence of blood-testis barrier (BTB) proteins TJP1 (ZO-1), occluding (OCLN) and CTNNB1 (beta-catenin) showed abnormal expression and discontinuous distribution of these proteins along the basement membrane, suggesting a collapse of BTB structure
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• immunostaining of actin and tubulin showed irregular arrangement and aberrant assembly of actin filaments, indicating impaired cytoskeletal organization in Sertoli cells (SCs)
• vimentin expression is completely disordered, as shown by the absence of directional polarity and loss of expression in some tubules
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• number of WT1-positive SCs is significantly decreased at 4 weeks, with an even greater reduction seen at 8 weeks
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• immunofluorescence of Wilm's tumor 1 (WT1, a nuclear marker for SCs) showed many SCs scattered over the seminiferous epithelium, even in tubules with many germ cells, indicating aberrant location and disrupted SC polarity
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• males exhibit age-dependent seminiferous tubule degeneration
• at 4 weeks, some tubules show loss of tubular cellular architecture and germ cells
• by 8 weeks, tubules display severe atrophy (13.6%), abnormal localization of sperm cells (40.1%), loss of cellular architecture and absence of tubular lumen (12.9%), severe vacuolization of the seminiferous epithelium, and a Sertoli cell-only phenotype with complete loss of germ cells (13.8%)
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• at 8 weeks of age, mRNA levels of several functional markers for germ cells, Leydig cells, and Sertoli cells (SCs) are significantly reduced
• protein levels of GATA4 (a transcription factor that plays a critical role in SC maturation and testis development) are abnormally increased at 4 weeks, whereas Gata4 mRNA levels remain normal
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small testis
(
J:289161
)
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• adult males have significantly smaller testes than controls males
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• testes weight is significantly reduced starting at 4 weeks of age
• by 8 weeks of age, testes weight is reduced by 67% relative to control testes
• however, body weight is normal at all ages examined
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• by 8 weeks of age, 13.6% of seminiferous tubules exhibit severe atrophy
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• males exhibit age-dependent testicular degeneration
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• at 8 weeks of age, males display severe spermatogenic defects, as shown by immunofluorescence of PNA (a marker for acrosome structure in the round and elongating spermatids), c-Kit (a marker for differentiating spermatogonia), and DDX4 (a general marker for germ cells)
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• adult males show a 10-fold increase in the number of epididymal tubules devoid of sperm
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• adult epididymal size is significantly reduced
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• adult epididymal weight is significantly reduced
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• when mated with wild-type females of proven fertility, males sire a significantly smaller litter size at 5 and 6 months of age, with no pups produced at 7 months
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• males become infertile by 7 months of age
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• males show an age-dependent decrease in fertility starting at 2 months of age
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cellular
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• males show progressive loss of germ cells in the seminiferous tubules from 4 weeks, with complete loss of germ cells by 8 weeks of age
|
|
|
• adult males show a 67% reduction in epididymal sperm count relative to control males
|
|
|
• at 8 weeks of age, germ cell proliferation is significantly reduced in the seminiferous epithelium, as shown by Ki-67 immunostaining
|
|
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• at 8 weeks of age, excessive germ cell apoptosis is detected by a TUNEL assay
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homeostasis/metabolism
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• plasma testosterone levels are normal at 4 weeks but severely reduced at 8 and 28 weeks of age
• reduced testosterone secretion is due to progressive Leydig cell inefficiency rather than progressive Leydig cell loss
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endocrine/exocrine glands
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• impaired cytoskeletal organization and cell polarity of Sertoli cells results in disruption of cell architecture throughout the seminiferous epithelium
|
|
|
• immunofluorescence of blood-testis barrier (BTB) proteins TJP1 (ZO-1), occluding (OCLN) and CTNNB1 (beta-catenin) showed abnormal expression and discontinuous distribution of these proteins along the basement membrane, suggesting a collapse of BTB structure
|
|
|
• immunostaining of actin and tubulin showed irregular arrangement and aberrant assembly of actin filaments, indicating impaired cytoskeletal organization in Sertoli cells (SCs)
• vimentin expression is completely disordered, as shown by the absence of directional polarity and loss of expression in some tubules
|
|
|
• number of WT1-positive SCs is significantly decreased at 4 weeks, with an even greater reduction seen at 8 weeks
|
|
|
• immunofluorescence of Wilm's tumor 1 (WT1, a nuclear marker for SCs) showed many SCs scattered over the seminiferous epithelium, even in tubules with many germ cells, indicating aberrant location and disrupted SC polarity
|
|
|
• males exhibit age-dependent seminiferous tubule degeneration
• at 4 weeks, some tubules show loss of tubular cellular architecture and germ cells
• by 8 weeks, tubules display severe atrophy (13.6%), abnormal localization of sperm cells (40.1%), loss of cellular architecture and absence of tubular lumen (12.9%), severe vacuolization of the seminiferous epithelium, and a Sertoli cell-only phenotype with complete loss of germ cells (13.8%)
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|
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• at 8 weeks of age, mRNA levels of several functional markers for germ cells, Leydig cells, and Sertoli cells (SCs) are significantly reduced
• protein levels of GATA4 (a transcription factor that plays a critical role in SC maturation and testis development) are abnormally increased at 4 weeks, whereas Gata4 mRNA levels remain normal
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small testis
(
J:289161
)
|
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• adult males have significantly smaller testes than controls males
|
|
|
• testes weight is significantly reduced starting at 4 weeks of age
• by 8 weeks of age, testes weight is reduced by 67% relative to control testes
• however, body weight is normal at all ages examined
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• by 8 weeks of age, 13.6% of seminiferous tubules exhibit severe atrophy
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• males exhibit age-dependent testicular degeneration
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