reproductive system
• most cauda epididymal sperm are morphologically abnormal
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• ~55% of sperm tails are curved/bent
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• roughly 50% of cauda sperm show deformed or detached heads
• ~55% of sperm show head and midpiece bent over the principal piece of the tail
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• headless sperm are observed
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• extensive male germ cell depletion is observed at P35
• germ cell depletion is progressively worse at 3, 7, and 21 months of age
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• males exhibit 7.4 times less cauda epididymal sperm than control males
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• diplotene-like spermatocytes display nonhomologous chromosome synapsis
• zygotene-like spermatocytes show nonhomologous chromosome synapsis, short chromosome length, and abnormal number of chromosomes
• pachytene-like spermatocytes show nonhomologous chromosome synapsis, with persistent gammaH2AX flares/foci on autosomes likely indicating unrepaired double-strand DNA breaks
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• TUNEL staining showed a significant increase in spermatocyte apoptosis
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• vacuole formation is observed within the seminiferous epithelium at P35
• at advanced ages, the seminiferous epithelium only consists of Sertoli cells
• onset of seminiferous epithelium pathology with reduced cellularity is at P12
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• at P35, the seminiferous tubule diameter appears narrower than in control males
• a 1.6-fold reduction in tubule cross-section diameter is seen at 3 months of age
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• atrophy of the seminiferous tubules, germ cell loss, and vacuole formation are observed at P35
• vacuole formation is progressively worse at 3, 7, and 21 months of age
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small testis
(
J:324061
)
• testis size is severely decreased at P35
|
• a 2.9-fold reduction in testis weight is seen at 3 months of age
|
• at P35, spermatogonia and a few meiotic cells can be seen but no round spermatids are detected
• at 3-4 months of age, flow cytometry data showed a significant decrease in 1N cells (round spermatids) and an increase in 2N (spermatogonia, Sertoli, peritubular, and Leydig cells) and 4N (primary spermatocytes) cells, indicating arrest in meiosis
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• spermatocytes show failure to complete prophase I of meiosis with arrest at the mid-pachytene stage
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• 3-month-old males are severely subfertile, producing a significantly lower number of litters than control males over a 6-month period (0.6 litters versus 6 litters, respectively)
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cellular
• most cauda epididymal sperm are morphologically abnormal
|
• ~55% of sperm tails are curved/bent
|
• roughly 50% of cauda sperm show deformed or detached heads
• ~55% of sperm show head and midpiece bent over the principal piece of the tail
|
• headless sperm are observed
|
• extensive male germ cell depletion is observed at P35
• germ cell depletion is progressively worse at 3, 7, and 21 months of age
|
• males exhibit 7.4 times less cauda epididymal sperm than control males
|
• zygotene-like spermatocytes show short chromosome length and abnormal number of chromosomes
• some pachytene-like spermatocytes show abnormally long chromosomes
|
• zygotene-like spermatocytes show abnormal number of chromosomes likely due to abnormal synapsis between nonhomologous chromosomes
|
• diplotene-like spermatocytes display nonhomologous chromosome synapsis
• zygotene-like spermatocytes show nonhomologous chromosome synapsis, short chromosome length, and abnormal number of chromosomes
• pachytene-like spermatocytes show nonhomologous chromosome synapsis, with persistent gammaH2AX flares/foci on autosomes likely indicating unrepaired double-strand DNA breaks
|
• spermatocytes show failure to complete prophase I of meiosis with arrest at the mid-pachytene stage
|
• TUNEL staining showed a significant increase in spermatocyte apoptosis
|
• pachytene-like spermatocytes with synapsis defects show gammaH2AX foci/flares on autosomes, indicating delayed DSB repair
|
endocrine/exocrine glands
• vacuole formation is observed within the seminiferous epithelium at P35
• at advanced ages, the seminiferous epithelium only consists of Sertoli cells
• onset of seminiferous epithelium pathology with reduced cellularity is at P12
|
• at P35, the seminiferous tubule diameter appears narrower than in control males
• a 1.6-fold reduction in tubule cross-section diameter is seen at 3 months of age
|
• atrophy of the seminiferous tubules, germ cell loss, and vacuole formation are observed at P35
• vacuole formation is progressively worse at 3, 7, and 21 months of age
|
small testis
(
J:324061
)
• testis size is severely decreased at P35
|
• a 2.9-fold reduction in testis weight is seen at 3 months of age
|
homeostasis/metabolism
• pachytene-like spermatocytes with synapsis defects show gammaH2AX foci/flares on autosomes, indicating delayed DSB repair
|