reproductive system
• only a few spermatogonia are detected in seminiferous tubules at P10
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• immunofluorescence analysis revealed a significantly reduced number of TRA98+ germ cells at P10, with only few seminiferous tubules containing germ cells by P20
• no germ cells are produced in tubules that contain immature (AMH+) Sertoli cells at P20
• however, population of germ cells is normal at E15.5
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• fewer germ cells are found in seminiferous tubules relative to controls at P10 and P20
• sloughing of cells into the lumen of the tubules is clearly detected at P20
• at P20, immature (AMH+) Sertoli cells are still present in many tubules, unlike in control testes; no germ cells are produced in such tubules, resulting in the formation of Sertoli cell-only tubules
• at P42, some tubules are completely devoid of germ cells and contain only Sertoli cells at the basal membrane
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• only a thin layer of seminiferous tubule epithelium is observed at P10, unlike in control testes where thickness of the germinal epithelium is increased
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• large increase in seminiferous tubular diameter and widened central lumen at P30 and P42
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• many seminiferous tubules undergo severe vacuolar degeneration at P42
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• Sertoli cell maturation is delayed, as indicated by persistent expression of AMH (an immature Sertoli cell marker) at P10, P20, P30, and P42, despite decreases in intensity
• at P20, germ cells are produced only in seminiferous tubules that do not express AMH, suggesting that immature Sertoli cells are unable to support developing germ cells even at puberty
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small testis
(
J:233398
)
• significantly reduced testis size at 6 weeks of age
• normal testis size at P2.5 with significant decrease in testis size from P10 onward
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• at 6 weeks of age, testis weight is reduced to ~25% of control values
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• down-regulation of androgen receptor (AR) responsive genes Rhox5 and Cldn3 in testes at P42
• however, despite delayed maturation of Sertoli cells, AR expression in Sertoli cells is normal at P10, P20, and P30
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• significant increase in testis apoptosis at P10, P20, and P30, as shown by TUNEL assays
• strikingly, ~60% seminiferous tubules are TUNEL+ at P10
• although number of TUNEL+ tubules decreases with age, apoptotic cells are still found in ~25% of tubules at P30
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• males exhibit delayed onset of spermatogenesis as well as impaired spermatogenic progression
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azoospermia
(
J:233398
)
• absence of mature spermatozoa in the epididymal lumen at P42
|
• no round spermatids are present in seminiferous tubules at P20, unlike in control testes
• only round spermatids, but no elongating spermatids, are present in tubules at P30, unlike in control testes
• no elongating spermatids are present in tubules at P42, unlike in control testes
• only few round spermatids are present in the epididymal lumen at P42
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• spermatogenic arrest at the round spermatid stage
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• significantly reduced epididymis size at 6 weeks of age
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• at 6 weeks of age, epididymis weight is reduced to ~65% of control values
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• males are completely infertile
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homeostasis/metabolism
• however, serum testosterone levels are normal
• males show significantly increased serum FSH levels at 2 months of age
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• males show significantly increased serum LH levels at 2 months of age
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endocrine/exocrine glands
• fewer germ cells are found in seminiferous tubules relative to controls at P10 and P20
• sloughing of cells into the lumen of the tubules is clearly detected at P20
• at P20, immature (AMH+) Sertoli cells are still present in many tubules, unlike in control testes; no germ cells are produced in such tubules, resulting in the formation of Sertoli cell-only tubules
• at P42, some tubules are completely devoid of germ cells and contain only Sertoli cells at the basal membrane
|
• only a thin layer of seminiferous tubule epithelium is observed at P10, unlike in control testes where thickness of the germinal epithelium is increased
|
• large increase in seminiferous tubular diameter and widened central lumen at P30 and P42
|
• many seminiferous tubules undergo severe vacuolar degeneration at P42
|
• Sertoli cell maturation is delayed, as indicated by persistent expression of AMH (an immature Sertoli cell marker) at P10, P20, P30, and P42, despite decreases in intensity
• at P20, germ cells are produced only in seminiferous tubules that do not express AMH, suggesting that immature Sertoli cells are unable to support developing germ cells even at puberty
|
small testis
(
J:233398
)
• significantly reduced testis size at 6 weeks of age
• normal testis size at P2.5 with significant decrease in testis size from P10 onward
|
• at 6 weeks of age, testis weight is reduced to ~25% of control values
|
• down-regulation of androgen receptor (AR) responsive genes Rhox5 and Cldn3 in testes at P42
• however, despite delayed maturation of Sertoli cells, AR expression in Sertoli cells is normal at P10, P20, and P30
|
• significant increase in testis apoptosis at P10, P20, and P30, as shown by TUNEL assays
• strikingly, ~60% seminiferous tubules are TUNEL+ at P10
• although number of TUNEL+ tubules decreases with age, apoptotic cells are still found in ~25% of tubules at P30
|
cellular
• no round spermatids are present in seminiferous tubules at P20, unlike in control testes
• only round spermatids, but no elongating spermatids, are present in tubules at P30, unlike in control testes
• no elongating spermatids are present in tubules at P42, unlike in control testes
• only few round spermatids are present in the epididymal lumen at P42
|
• only a few spermatogonia are detected in seminiferous tubules at P10
|
• immunofluorescence analysis revealed a significantly reduced number of TRA98+ germ cells at P10, with only few seminiferous tubules containing germ cells by P20
• no germ cells are produced in tubules that contain immature (AMH+) Sertoli cells at P20
• however, population of germ cells is normal at E15.5
|
azoospermia
(
J:233398
)
• absence of mature spermatozoa in the epididymal lumen at P42
|
• significant increase in testis apoptosis at P10, P20, and P30, as shown by TUNEL assays
• strikingly, ~60% seminiferous tubules are TUNEL+ at P10
• although number of TUNEL+ tubules decreases with age, apoptotic cells are still found in ~25% of tubules at P30
|