reproductive system
• testes show significant vacuolization of male germ cells
• defects in spermiogenesis and spermiation result in degeneration and rapid reabsorption of elongating/elongated spermatids in testes
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• phosphoproteomics analysis of purified testicular germ cells showed significantly reduced phosphorylation of multiple infertility-related proteins, including GAPDHS, ACTL7A, ACTL9 and REEP6
• however, total protein levels remain unaffected
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• all stages of the seminiferous epithelium cycle (I-XII) show some form of disorganization; most tubule cross-sections contain germ cells that appear to be either too early or too late for that stage
• however, both testis size and weight are normal
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• ~28.7% of seminiferous tubule cross-sections exhibit vacuolization versus only ~1.5% in controls
• omitting stages VII and VIII, ~92% of all circular tubule cross-sections that contain vacuolization are at stages IV-VI and ~8% are at stage IX
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• histological and ultrastructural analysis showed obvious defects in late spermatogenesis
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• caudal epididymal sperm count is nearly ablated relative to that in heterozygous control males
• epididymis histology revealed only a few sperm present in the lumen
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• cauda epididymal sperm appear morphologically abnormal
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• all of the few spermatozoa retrieved from the epididymis exhibit thin sperm midpieces
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• all of the few spermatozoa retrieved from the epididymis exhibit amorphous head morphology
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• at steps 14 and 15, spermatids show unstructured acrosome morphology and degradation
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• acrosomes are detached from the sperm nuclei
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• at steps 14 and 15, spermatids show unstructured manchette morphology and degradation
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• step 14-15 spermatids exhibit excess cytoplasm around normal-shaped nuclei
• early elongating spermatids that are typical of stage IX are instead observed at XII
• elongating spermatids that should have been fully developed at stage I appear underdeveloped
• elongated spermatids do not line the lumen at stage VII; stages VII and VIII are difficult to ascertain through standard staging criteria
• elongated spermatids fail to proceed normally along the spermiation pathway, resulting in a higher distribution of stages I-VI
• however, tubules progress to stage IX as irregularly shaped round spermatids can be found
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• elongated spermatids that should have undergone spermiation at stage VIII are frequently observed at later stages IX-XI, with unreleased fully elongated spermatids still embedded in the epithelium
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• male mice fail to sire pups when mated with wild-type females for >4 months, indicating complete male sterility
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cellular
• testes show significant vacuolization of male germ cells
• defects in spermiogenesis and spermiation result in degeneration and rapid reabsorption of elongating/elongated spermatids in testes
|
• caudal epididymal sperm count is nearly ablated relative to that in heterozygous control males
• epididymis histology revealed only a few sperm present in the lumen
|
• cauda epididymal sperm appear morphologically abnormal
|
• all of the few spermatozoa retrieved from the epididymis exhibit thin sperm midpieces
|
• all of the few spermatozoa retrieved from the epididymis exhibit amorphous head morphology
|
• at steps 14 and 15, spermatids show unstructured acrosome morphology and degradation
|
• acrosomes are detached from the sperm nuclei
|
• at steps 14 and 15, spermatids show unstructured manchette morphology and degradation
|
• phosphoproteomics analysis of purified testicular germ cells showed significantly reduced phosphorylation of multiple infertility-related proteins, including GAPDHS, ACTL7A, ACTL9 and REEP6
• however, total protein levels remain unaffected
|
endocrine/exocrine glands
• all stages of the seminiferous epithelium cycle (I-XII) show some form of disorganization; most tubule cross-sections contain germ cells that appear to be either too early or too late for that stage
• however, both testis size and weight are normal
|
• ~28.7% of seminiferous tubule cross-sections exhibit vacuolization versus only ~1.5% in controls
• omitting stages VII and VIII, ~92% of all circular tubule cross-sections that contain vacuolization are at stages IV-VI and ~8% are at stage IX
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