Analysis Tools
reproductive system
azoospermia
(
J:276385
)
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• males exhibit aspermia at 28 weeks of age
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• spermatocytes show fewer and less intense axial foci of REC114 genome-wide throughout prophase I; REC114 no longer forms blobs on the pseudoautosomal region (PAR) or other regions
• metaphase I spermatocytes frequently show unaligned chromosomes
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• high frequency of unpaired and/or achiasmate sex chromosomes is the likely cause of arrest at metaphase I
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• immunostaining for SYCP3 and the synaptonemal complex (SC) central region protein SYCP1 shows that 14% of pachytene-like spermatocytes show a mix of fully synapsed autosomes plus asynaptic chromosomes and/or chromosome tangles (i.e., a mix of synapsed and unsynapsed axes with partner switches indicating non-homologous synapsis)
• interchromosome end associations are also observed
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• mice show delayed double-strand breaks (DSB) formation and recombination, defects in DSB repair, and altered DSB locations including failure to target DSBs to the PARs
• fewer and/or delayed sites marked by recombination proteins but, paradoxically, more DSBs are observed, as measured by SPO11-oligo complexes
• spermatocytes have little or no use of PRDM9-independent (default) DSB sites in the PAR and show a mixed usage of both PRDM9-dependent and default DSB sites elsewhere in the genome
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• sex chromosomes fail to pair in 92% of otherwise normal-looking pachytene cells
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• at 4 months of age, TUNEL staining shows that ~23% of tubules contain dying pachytene spermatocytes while ~65% of tubules contain dying metaphase I cells
• partially penetrant pachytene apoptosis is likely due to a combination of persistent DSBs and synaptic defects
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• oogenesis is significantly reduced
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• females show greatly reduced oocyte numbers both at 1-4 days postpartum (dpp) and at 32 dpp, indicating a smaller oocyte reserve; a significantly lower oocyte number is noted at 15 weeks of age
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• females exhibit fewer primordial follicles than controls at 32 dpp
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• a reduced number of follicles is noted at 15 weeks of age; all follicle types are absent in the ovaries at 24 weeks of age
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small ovary
(
J:276385
)
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• ovary size is significantly decreased by ~8 months of age
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• adult seminiferous tubules contain spermatogonia and primary spermatocytes but are almost completely devoid of post-meiotic cells (round and elongated spermatids)
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• at 28 weeks of age, seminiferous tubules show marked degeneration with aspermia
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small testis
(
J:276385
)
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• adult testis size is significantly smaller at 4 months of age
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• adult testis weight is 37% of that in control males
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• young adult females are fertile but exhibit a small oocyte reserve and premature ovarian failure
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• males show a mixed arrest of spermatogenesis - partial in pachynema and more complete in metaphase I
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• unrepaired DSBs and pairing failures, stochastic on autosomes and almost absolute on X and Y, lead to meiotic arrest and sterility in males
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• males fail to sire offspring when bred with wild-type females for 16 weeks
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cellular
azoospermia
(
J:276385
)
|
|
• males exhibit aspermia at 28 weeks of age
|
|
|
• spermatocytes show fewer and less intense axial foci of REC114 genome-wide throughout prophase I; REC114 no longer forms blobs on the pseudoautosomal region (PAR) or other regions
• metaphase I spermatocytes frequently show unaligned chromosomes
|
|
|
• high frequency of unpaired and/or achiasmate sex chromosomes is the likely cause of arrest at metaphase I
|
|
|
• immunostaining for SYCP3 and the synaptonemal complex (SC) central region protein SYCP1 shows that 14% of pachytene-like spermatocytes show a mix of fully synapsed autosomes plus asynaptic chromosomes and/or chromosome tangles (i.e., a mix of synapsed and unsynapsed axes with partner switches indicating non-homologous synapsis)
• interchromosome end associations are also observed
|
|
|
• mice show delayed double-strand breaks (DSB) formation and recombination, defects in DSB repair, and altered DSB locations including failure to target DSBs to the PARs
• fewer and/or delayed sites marked by recombination proteins but, paradoxically, more DSBs are observed, as measured by SPO11-oligo complexes
• spermatocytes have little or no use of PRDM9-independent (default) DSB sites in the PAR and show a mixed usage of both PRDM9-dependent and default DSB sites elsewhere in the genome
|
|
|
• sex chromosomes fail to pair in 92% of otherwise normal-looking pachytene cells
|
|
|
• unrepaired DSBs and pairing failures, stochastic on autosomes and almost absolute on X and Y, lead to meiotic arrest and sterility in males
|
|
|
• at 4 months of age, TUNEL staining shows that ~23% of tubules contain dying pachytene spermatocytes while ~65% of tubules contain dying metaphase I cells
• partially penetrant pachytene apoptosis is likely due to a combination of persistent DSBs and synaptic defects
|
|
|
• oogenesis is significantly reduced
|
|
|
• females show greatly reduced oocyte numbers both at 1-4 days postpartum (dpp) and at 32 dpp, indicating a smaller oocyte reserve; a significantly lower oocyte number is noted at 15 weeks of age
|
|
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• pachytene cells with apparently normal autosome synapsis frequently show discrete flares of persistent gammaH2AX staining and elevated DMC1, RAD51, and RPA foci, suggesting that many cells contain incompletely repaired DSBs
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endocrine/exocrine glands
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• females exhibit fewer primordial follicles than controls at 32 dpp
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• a reduced number of follicles is noted at 15 weeks of age; all follicle types are absent in the ovaries at 24 weeks of age
|
small ovary
(
J:276385
)
|
|
• ovary size is significantly decreased by ~8 months of age
|
|
|
• adult seminiferous tubules contain spermatogonia and primary spermatocytes but are almost completely devoid of post-meiotic cells (round and elongated spermatids)
|
|
|
• at 28 weeks of age, seminiferous tubules show marked degeneration with aspermia
|
small testis
(
J:276385
)
|
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• adult testis size is significantly smaller at 4 months of age
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• adult testis weight is 37% of that in control males
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• young adult females are fertile but exhibit a small oocyte reserve and premature ovarian failure
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homeostasis/metabolism
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• pachytene cells with apparently normal autosome synapsis frequently show discrete flares of persistent gammaH2AX staining and elevated DMC1, RAD51, and RPA foci, suggesting that many cells contain incompletely repaired DSBs
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mortality/aging
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• young adult females are fertile but exhibit a small oocyte reserve and premature ovarian failure
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