Analysis Tools
reproductive system
 N |
• female mice exhibit normal fertility
(J:328252)
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 N |
• absolute and relative weight of testes and epididymis are normal and overall cauda epididymis morphology is unaffected
(J:328252)
• testicular seminiferous tubules show normal actin cytoskeleton organization
(J:328252)
• testes show no evidence of male germ cell apoptosis or phagocytosis of germ cells by Sertoli cells
(J:328252)
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• impaired manchette development results in abnormal sperm flagellum structural defects
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• cauda epididymal sperm show cytoplasmic droplets in the connecting piece as well as a bent connecting piece
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• cauda epididymal sperm show cytoplasmic droplets in the midpiece, a bent midpiece, and an abnormally shortened thick midpiece
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• cauda epididymal sperm show an abnormal fibrous sheath with mitochondrial structural defects
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necrospermia
(
J:328252
)
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• eosin and nigrosine (E&N) staining of mature cauda epididymal sperm show an abnormally low % of viable sperm (25%) relative to heterozygous and wild-type control males (60-80%)
• hypo-osmotic swelling test (where tail curling = live sperm cells) show an abnormally low % of hypo-osmotic reactive sperm (24%) relative to control males
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• 77% of mature cauda epididymal sperm display a severely disturbed, irregular/round head shape and smaller head size
• 16% of sperm exhibit a less aberrant head shape that is similar to that seen in control sperm
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• abnormal acrosome biogenesis with fragmented Golgi network in spermatids
• mature sperm isolated from the cauda epididymis display malformed acrosomes
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• acrosome biogenesis is impaired due to disruption of cis- and trans-Golgi networks and aberrant production of proacrosomal vesicles
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• round spermatids fail to properly fuse proacrosomal granules/vesicles to form the acrosome
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• elongating spermatozoa exhibit smaller nuclei
• sperm nuclear area, perimeter, regularity, bounding width and circularity are significantly altered
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• amorphous and smaller head shape
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• elongating spermatozoa appear misshapen with apparently smaller nuclei
• step 11-13 spermatids lack the typical parallel microtubular array structure of the manchette and appear scraggy and rugged in shape
• step 12-16 spermatids show a complete loss of the manchette and amorphous head shape
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• spermatids exhibit mis-localization (steps 8-9) and an angular shape (step 10) of the microtubular manchette
• in steps 11-13, spermatids completely lack the microtubular array structure
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• manchette formation is disrupted leading to deformed sperm heads and flagellar defects
• however, perinuclear ring formation is not affected
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• in some cases, the manchette appears to be absent
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• CASA analysis revealed a significant reduction in total sperm motility
• curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity (VAP) and progressive motility are significantly reduced
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• proteins involved in Golgi membrane trafficking and the PI3K/AKT pathway (ARF3, SPECC1L and FKBP1) are more abundant in the testes
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• all adult males fail to produce pregnancy or offspring
• however, mating behavior is normal as vaginal plugs are clearly observed
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• sperm are unable to fertilize wild-type oocytes with an intact zona pellucida in IVF assays
• however, when sperm are incubated with wild-type zona-free eggs, 30% of oocytes are successfully fertilized and develop to the morula/blastocyst stage
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• in vitro, the rate of A23187-induced acrosome reaction is severely reduced, with only 5-6% of sperm exhibiting acrosome exocytosis versus 72% and 65% of sperm from wild-type and heterozygous controls, respectively
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cellular
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N |
• testes exhibit no organizational defects in the actin cytoskeleton; no differences in male germ cell apoptosis are observed relative to controls
|
|
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• impaired manchette development results in abnormal sperm flagellum structural defects
|
|
|
• cauda epididymal sperm show cytoplasmic droplets in the connecting piece as well as a bent connecting piece
|
|
|
• cauda epididymal sperm show cytoplasmic droplets in the midpiece, a bent midpiece, and an abnormally shortened thick midpiece
|
|
|
• cauda epididymal sperm show an abnormal fibrous sheath with mitochondrial structural defects
|
necrospermia
(
J:328252
)
|
|
• eosin and nigrosine (E&N) staining of mature cauda epididymal sperm show an abnormally low % of viable sperm (25%) relative to heterozygous and wild-type control males (60-80%)
• hypo-osmotic swelling test (where tail curling = live sperm cells) show an abnormally low % of hypo-osmotic reactive sperm (24%) relative to control males
|
|
|
• 77% of mature cauda epididymal sperm display a severely disturbed, irregular/round head shape and smaller head size
• 16% of sperm exhibit a less aberrant head shape that is similar to that seen in control sperm
|
|
|
• abnormal acrosome biogenesis with fragmented Golgi network in spermatids
• mature sperm isolated from the cauda epididymis display malformed acrosomes
|
|
|
• acrosome biogenesis is impaired due to disruption of cis- and trans-Golgi networks and aberrant production of proacrosomal vesicles
|
|
|
• round spermatids fail to properly fuse proacrosomal granules/vesicles to form the acrosome
|
|
|
• elongating spermatozoa exhibit smaller nuclei
• sperm nuclear area, perimeter, regularity, bounding width and circularity are significantly altered
|
|
|
• amorphous and smaller head shape
|
|
|
• elongating spermatozoa appear misshapen with apparently smaller nuclei
• step 11-13 spermatids lack the typical parallel microtubular array structure of the manchette and appear scraggy and rugged in shape
• step 12-16 spermatids show a complete loss of the manchette and amorphous head shape
|
|
|
• spermatids exhibit mis-localization (steps 8-9) and an angular shape (step 10) of the microtubular manchette
• in steps 11-13, spermatids completely lack the microtubular array structure
|
|
|
• manchette formation is disrupted leading to deformed sperm heads and flagellar defects
• however, perinuclear ring formation is not affected
|
|
|
• in some cases, the manchette appears to be absent
|
|
|
• spermatids display defective Golgi networks in testis sections: the cis-Golgi network is structurally disrupted and mildly mis-localized while the trans-Golgi network is fragmented and dispersed throughout the cytoplasm
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• testicular protein levels of PI3K, AKT and mTOR are elevated whereas AMPK level is reduced, resulting in autophagy inhibition
• moreover, testicular protein levels of LC3BI/II (a marker for autophagy activation) and SQSTM1 (a marker for autophagic/lysosomal degradation) are increased, suggesting that accumulation of autophagosomes leads to blockage of the autophagic flux
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• CASA analysis revealed a significant reduction in total sperm motility
• curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity (VAP) and progressive motility are significantly reduced
|
|
|
• spermatids display disorganization of the cis- and trans-Golgi networks, indicating impaired vesicle trafficking and transport
• proteins involved in Golgi membrane trafficking and the PI3K/AKT pathway (ARF3, SPECC1L and FKBP1) are more abundant in the testes
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homeostasis/metabolism
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• testicular protein levels of PI3K, AKT and mTOR are elevated whereas AMPK level is reduced, resulting in autophagy inhibition
• moreover, testicular protein levels of LC3BI/II (a marker for autophagy activation) and SQSTM1 (a marker for autophagic/lysosomal degradation) are increased, suggesting that accumulation of autophagosomes leads to blockage of the autophagic flux
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endocrine/exocrine glands
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• proteins involved in Golgi membrane trafficking and the PI3K/AKT pathway (ARF3, SPECC1L and FKBP1) are more abundant in the testes
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