reproductive system
• marker analysis indicates that the earliest self-renewing spermatogonial stem cells are not changed, whereas total spermatogonia are reduced
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• slight increase in apoptotic cells in the testis, but no changes in Sertoli cells, suggesting that mainly germ cells are affected
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• spermatocytes, round spermatids, and elongating spermatids show reduced mitochondrial membrane potential and cellular ATP content, indicating disrupted mitochondrial function during earlier spermatogenesis stages
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• male gonads weigh about 1/3 less than in wild-type mice at 1 month of age
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• mice show reduced spermatogenesis before meiosis starts, however spermatocytes can still complete meiosis
• while no differences in spermatogenic cells are seen at 1-week, post-meiotic spermatids (1N) are reduced at 4 weeks during the first wave of spermatogenesis and the number of SYCP3+ spermatocytes is reduced at 2 weeks and in adult mice
• however, no changes in the proportion of spermatocytes at meiosis I and II stages or during the prophase of meiosis I are seen, suggesting that meiotic progression is not affected
• decrease in PLZFLowcKIT+ differentiating spermatogonial stem cells
• testes treated with busulfan to apply chemotoxic insult show reduced regenerative spermatogenesis compared to wild-type testes
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• numbers of sperm in the cauda epididymis (mature sperm) are reduced in adult males
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• sperm morphology is abnormal and includes frequently bent heads
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• sperm show disoriented outer dense fiber
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• sperm show disorganized axoneme
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• sperm contain malformed mitochondria sheath, containing hollow matrix and electron dense aggregates
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• proliferation of spermatogonial cells is reduced
• PLZFLow spermatogonial stem cells, but not PLZFHigh spermatogonial stem cells, are reduced, indicating that proliferative spermatogonial stem cells are decreased when entering differentiation state
• PLZFLow spermatogonial stem cells contain decreased Ki67+ and increased Ki67- cells, indicating decreased proliferation
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• males sire about 50% less frequently in a recorded period of 3 months, although the average number of pups in each litter is only slightly reduced
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• cauda epididymal sperm show reduced mitochondrial membrane potential and cellular ATP content, indicating reduced mitochondrial function
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• sperm are less motile
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endocrine/exocrine glands
• slight increase in apoptotic cells in the testis, but no changes in Sertoli cells, suggesting that mainly germ cells are affected
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• male gonads weigh about 1/3 less than in wild-type mice at 1 month of age
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cellular
• numbers of sperm in the cauda epididymis (mature sperm) are reduced in adult males
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• sperm morphology is abnormal and includes frequently bent heads
|
• sperm show disoriented outer dense fiber
|
• sperm show disorganized axoneme
|
• sperm contain malformed mitochondria sheath, containing hollow matrix and electron dense aggregates
|
• marker analysis indicates that the earliest self-renewing spermatogonial stem cells are not changed, whereas total spermatogonia are reduced
|
• slight increase in apoptotic cells in the testis, but no changes in Sertoli cells, suggesting that mainly germ cells are affected
|
• sperm are less motile
|
• proliferation of spermatogonial cells is reduced
• PLZFLow spermatogonial stem cells, but not PLZFHigh spermatogonial stem cells, are reduced, indicating that proliferative spermatogonial stem cells are decreased when entering differentiation state
• PLZFLow spermatogonial stem cells contain decreased Ki67+ and increased Ki67- cells, indicating decreased proliferation
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• spermatocytes, round spermatids, and elongating spermatids show reduced mitochondrial membrane potential and cellular ATP content, indicating disrupted mitochondrial function during earlier spermatogenesis stages
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• testicular cells contain about 10% higher levels of reactive oxygen species than wild-type cells
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