mortality/aging
• on a pure C57BL/6 background, young males are initially fertile but become infertile by 11 weeks of age
• on a pure C57BL/6 background, no litters are born to males after the first month of mating
• Background Sensitivity: unlike adult males on a pure C57BL/6 background, some males are still fertile on a mixed background involving 129/Sv and C57BL/6
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reproductive system
• at P8, fewer male germ cells are detected in the testes
• at 8 weeks of age, some seminiferous tubules are clearly devoid of sperm
• by 8 months of age, males are infertile and exhibit seminiferous tubules that with few exceptions are completely devoid of sperm
• loss of male germ cells is detected as early as P2 and is cell autonomous and inherent to the germ cells
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• by 12 weeks of age, sperm motility is severely impaired
• however, only mild changes in sperm motility are observed in fertile males at 8 weeks of age
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• after the first round of spermatogenesis, seminiferous tubules degenerate and become completely devoid of germ cells by 8 months of age
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• by 8 months of age, males display Leydig cell hyperplasia that is secondary to germ cell loss
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small testis
(
J:97245
)
• at 6 weeks of age, testes are significantly smaller than heterozygous control testes
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• testis weights are lower than those of heterozygous controls as early as 3 weeks of age
• at 6 weeks of age, testes weigh ~58.1 mg while those of heterozygous controls weigh on average ~81.1 mg
• by 12 weeks of age, testis weights are only 40% of those in heterozygous controls
|
• on a pure C57BL/6 background, young males are initially fertile but become infertile by 11 weeks of age
• on a pure C57BL/6 background, no litters are born to males after the first month of mating
• Background Sensitivity: unlike adult males on a pure C57BL/6 background, some males are still fertile on a mixed background involving 129/Sv and C57BL/6
|
• adult males fail to maintain spermatogenesis, probably due to defects in spermatogonial stem cell function
• however, transplanted wild-type germ cell stem cells are able to colonize in seminiferous tubules of adult germ cell-depleted mutant mice
|
• by 12 weeks of age, males show a ~10-fold reduction in epididymal sperm count relative to heterozygous controls
• however, only mild changes in sperm count are observed in fertile males at 8 weeks of age
|
• at P2, gonocyte proliferation is impaired and expression of spermatogonial stem cell markers is reduced
• at P3, only 26.6% of seminiferous tubules contain phospho-histone H3 positive cells relative to 45.4% and 47.6% of wild-type and heterozygous tubules, respectively
• by P8, only 3.8 spermatogonia are found in seminiferous tubules relative to 14.4 and 14.9 in wild-type and heterozygous tubules, respectively
• however, no differences in TUNEL staining are observed in testes at P3 or in adulthood
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• by 8 weeks of age, males show clear defects in spermiogenesis
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• by 12 weeks of age, acrosome cap formation is severely impaired
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• on a pure C57BL/6 background, young males are initially fertile but become infertile by 11 weeks of age
|
endocrine/exocrine glands
• after the first round of spermatogenesis, seminiferous tubules degenerate and become completely devoid of germ cells by 8 months of age
|
• by 8 months of age, males display Leydig cell hyperplasia that is secondary to germ cell loss
|
small testis
(
J:97245
)
• at 6 weeks of age, testes are significantly smaller than heterozygous control testes
|
• testis weights are lower than those of heterozygous controls as early as 3 weeks of age
• at 6 weeks of age, testes weigh ~58.1 mg while those of heterozygous controls weigh on average ~81.1 mg
• by 12 weeks of age, testis weights are only 40% of those in heterozygous controls
|
homeostasis/metabolism
• at 8-9 weeks of age, but not prior to 7 weeks of age, males show increased serum FSH levels relative to heterozygous controls
• in contrast, serum levels of LH and testosterone remain unaffected at all ages examined
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cellular
• by 12 weeks of age, acrosome cap formation is severely impaired
|
• at P8, fewer male germ cells are detected in the testes
• at 8 weeks of age, some seminiferous tubules are clearly devoid of sperm
• by 8 months of age, males are infertile and exhibit seminiferous tubules that with few exceptions are completely devoid of sperm
• loss of male germ cells is detected as early as P2 and is cell autonomous and inherent to the germ cells
|
• by 12 weeks of age, males show a ~10-fold reduction in epididymal sperm count relative to heterozygous controls
• however, only mild changes in sperm count are observed in fertile males at 8 weeks of age
|
• by 12 weeks of age, sperm motility is severely impaired
• however, only mild changes in sperm motility are observed in fertile males at 8 weeks of age
|
• at P2, gonocyte proliferation is impaired and expression of spermatogonial stem cell markers is reduced
• at P3, only 26.6% of seminiferous tubules contain phospho-histone H3 positive cells relative to 45.4% and 47.6% of wild-type and heterozygous tubules, respectively
• by P8, only 3.8 spermatogonia are found in seminiferous tubules relative to 14.4 and 14.9 in wild-type and heterozygous tubules, respectively
• however, no differences in TUNEL staining are observed in testes at P3 or in adulthood
|