homeostasis/metabolism
• in culture, primary Sertoli cells isolated from 3-mo-old testes fail to show apoAI-dependent cholesterol efflux in the presence of LXR/RXR agonists, whereas wild-type cells show a 1.4-fold increase in apoAI-dependent cholesterol efflux
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• strong reduction of plasma beta-sitosterol and campesterol levels
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• intratesticular testosterone levels are significantly decreased by 6 months of age
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• lack of circulating HDL suggests that steroidogenesis is supported by de novo synthesis of cholesterol
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• mice have virtually no circulating HDL
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reproductive system
• cauda epididymal sperm count is significantly reduced by 6 months of age
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• males show age-dependent accumulation of lipids in the seminiferous tubules, whereas no lipid accumulations are observed in wild-type tubules up to 24 months of age
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• accumulation of lipid droplets is seen near the base of the seminiferous epithelium at 7 months of age
• when large lipid droplets are present, a thickened tubule wall is observed
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• abnormally large lipid droplets are present in the cytoplasm of Sertoli cells at 2 months of age, with significantly more extensive lipid deposition seen at 11- and 12 months of age
• when large lipid droplets are present, nuclear indentation may be observed
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• inability to efflux lipids from Sertoli cells leads to variable amounts of tubule vacuolization and degeneration seen at 11 and 12 months of age
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• at 2 months of age, Leydig cells are abnormally depleted of lipid droplets, show clumping of the smooth endoplasmic reticulum, and extensive invaginations of the nuclear membrane or increased chromatin condensation and margination
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• males show a 21% reduction in their ability to sire offspring relative to age-matched wild-type controls over their reproductive lifespans
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cellular
• cauda epididymal sperm count is significantly reduced by 6 months of age
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• in culture, primary Sertoli cells isolated from 3-mo-old testes fail to show apoAI-dependent cholesterol efflux in the presence of LXR/RXR agonists, whereas wild-type cells show a 1.4-fold increase in apoAI-dependent cholesterol efflux
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endocrine/exocrine glands
• males show age-dependent accumulation of lipids in the seminiferous tubules, whereas no lipid accumulations are observed in wild-type tubules up to 24 months of age
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• accumulation of lipid droplets is seen near the base of the seminiferous epithelium at 7 months of age
• when large lipid droplets are present, a thickened tubule wall is observed
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• abnormally large lipid droplets are present in the cytoplasm of Sertoli cells at 2 months of age, with significantly more extensive lipid deposition seen at 11- and 12 months of age
• when large lipid droplets are present, nuclear indentation may be observed
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• inability to efflux lipids from Sertoli cells leads to variable amounts of tubule vacuolization and degeneration seen at 11 and 12 months of age
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• at 2 months of age, Leydig cells are abnormally depleted of lipid droplets, show clumping of the smooth endoplasmic reticulum, and extensive invaginations of the nuclear membrane or increased chromatin condensation and margination
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