Analysis Tools
reproductive system
 N |
• female mice are fertile
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• at 4 months of age, a significant proportion of cauda epididymal spermatozoa appear morphologically abnormal
• abnormal sperm morphology appears during transit from the head to the tail of the epididymis
• however, the morphology of sperm collected from testis is normal
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• TEM analysis of cauda epididymal sperm showed that the midpiece consists of disrupted mitochondria and axoneme wrapped around the bent head and neck
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• disrupted mitochondria are observed in the midpiece
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• phase contrast images revealed many cauda epididymal sperm with misshapen heads
• SEM showed that some cauda epididymal sperm heads have a roughly uneven surface and bend over with the tip of the head toward the tail or curl like a golf stick; other sperm curl as a disk-like structure by wrapping around the head with the neck and middle parts of the tail
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• at 4 months of age, the % of progressively motile sperm is significantly lower than that in wild-type males
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• at 4 months of age, the % of motile cauda epididymal sperm is significantly lower than that in wild-type males
• however, cauda epididymal sperm concentration is relatively normal
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(J:207622)
• when bred with female heterozygotes over a period of 6 months, most male heterozygotes (26/30) at ages of 2-8 months are unable to father a litter
(J:284227)
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• when bred with female heterozygotes over a period of 6 months, only ~13% of male heterozygotes (4/30) are able to father a litter with 2-4 pups per litter at earlier ages
• even when bred with wild-type females, only ~30% of male heterozygotes (3/10) are capable of fathering a litter, indicating severely impaired male fertility
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• at 13-15 months of age, expression of interleukin-6 (IL-6) is significantly increased in the epididymis relative to that in age-matched wild-type males
• at 4.5 months of age, IHC staining showed a significantly higher IL-6 expression in the epithelial cells of the caput, corpus and cauda of the epididymis than in wild-type epididymis
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homeostasis/metabolism
| N |
• mice exhibit normal serum insulin, triglyceride and free fatty acid levels
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• at 6 weeks in male, but not female, mice
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• increased circulating alpha-fetal protein at 6 and 12 months in male mice
• however, levels are normal at 2 months
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• at 6 and 12 months in male mice
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• early-onset at 6 weeks in male, but not female, mice
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• at 6 weeks in male, but not female, mice
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• in male, but not female, mice at 10 months
• however, levels at 6 month are normal
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liver/biliary system
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• in male mice
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• in male mice
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• chronic in male, but not female, mice with immune cell infiltrations around the bile ducts and in the portal areas, focal aggregates of lymphocytes, neutrophils and macrophage
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• at 6 or 10 months, male mice exhibit dysplasia with disorganized architecture, cytological atypia, enlarged nuclei and vacuolated hepatocytes compare with wild-type and female mice
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• in male, but not female, mice at 10 months
• however, levels at 6 month are normal
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• in male, but not female, mice at 6 or 10 months
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• in the periportal and periductular areas of male mice at 10 months
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• at 10 to 18 months, nearly all male mice develop spontaneous liver tumors (well to moderately differentiated HCC) with occasional lung metastasis unlike female or wild-type mice
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neoplasm
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• at 10 to 18 months, nearly all male mice develop spontaneous liver tumors (well to moderately differentiated HCC) with occasional lung metastasis unlike female or wild-type mice
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immune system
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• chronic in male, but not female, mice with immune cell infiltrations around the bile ducts and in the portal areas, focal aggregates of lymphocytes, neutrophils and macrophage
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cellular
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• at 4 months of age, a significant proportion of cauda epididymal spermatozoa appear morphologically abnormal
• abnormal sperm morphology appears during transit from the head to the tail of the epididymis
• however, the morphology of sperm collected from testis is normal
|
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• TEM analysis of cauda epididymal sperm showed that the midpiece consists of disrupted mitochondria and axoneme wrapped around the bent head and neck
|
|
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• disrupted mitochondria are observed in the midpiece
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|
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• phase contrast images revealed many cauda epididymal sperm with misshapen heads
• SEM showed that some cauda epididymal sperm heads have a roughly uneven surface and bend over with the tip of the head toward the tail or curl like a golf stick; other sperm curl as a disk-like structure by wrapping around the head with the neck and middle parts of the tail
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• in male mice
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• at 4 months of age, the % of progressively motile sperm is significantly lower than that in wild-type males
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• at 4 months of age, the % of motile cauda epididymal sperm is significantly lower than that in wild-type males
• however, cauda epididymal sperm concentration is relatively normal
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• in male mice
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endocrine/exocrine glands
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• in male mice at 8 and 24 weeks
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• decreased mass in male mice at 8 and 24 weeks
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