Analysis Tools
reproductive system
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• at 3- to 16-weeks of age, the median number of cells positive for TRA98 (a germ cell marker) is decreased
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• testes display atrophy of the seminiferous tubules; the median number of tubules per visual field is 3.8 times greater than in wild-type testes
• median thickness of the tubule walls is 1.4-fold larger as determined by alpha-smooth muscle actin (alpha-SMA) staining (a marker of peritubular myoid cells), and 1.75 times larger as determined by CD34 staining (a marker of telocytes)
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• testes show disrupted distribution of alpha-SMA-positive peritubular myoid cells (PTMCs)
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• at 3- to 16-weeks of age, the median number of Sox9-positive Sertoli cells per visual field is markedly increased
• when normalized by the number of seminiferous tubules, the number of Sox9-positive Sertoli cells is 1.5 times higher than in wild-type controls
• moreover, the number of Sox9-positive Sertoli cells per seminiferous tubule is increased by 1.3 times
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• seminiferous tubules show a significantly smaller cross-sectional area than wild-type tubules
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• testicular tissue shows an expanded interstitial area mainly due to an increase in Leydig cells: the median area of interstitium per visual field of thin testicular tissue sections is significantly greater than that in wild-type controls
• distribution of telocytes (an important component of testicular interstitium) is disrupted, as visualized by CD34 expression around the seminiferous tubules
• median fluorescent signal of NR5A1 (nuclear receptor subfamily 5, group A, member 1, aka Ad4BP) in the testicular interstitium is 1.9-fold higher than in wild-type testes
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• at 3- to 16-weeks of age, Leydig cell number is increased within the expanded interstitium; the median number of Ad4BP-expressing Leydig cells per visual field is increased by >7.2-fold
• when normalized by the number of seminiferous tubules, the number of Leydig cells is increased by 1.9 times
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small testis
(
J:360728
)
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• 3- to 16-week-old males exhibit strikingly smaller testes than heterozygous mice
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• testes display atrophy of the seminiferous tubules
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• testosterone synthesis is significantly increased in the testes, as shown by upregulation of genes involved in the testosterone synthesis pathway (Hsd17b3, Hsd3b1, Cyp11a1, and Cyp17a1)
• at 13-16 weeks of age, immunofluorescence staining of seminiferous tubule sections shows that the median signal intensity of Cyp17a1 is 3.46-fold lower at the single-cell level, whereas that of Hsd3b1 is significantly higher than in wild-type samples, suggesting that changes in testosterone levels produce different feedback effects on steroidogenic enzymes
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• 3- to 16-week-old males exhibit impaired spermatogenesis
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azoospermia
(
J:360728
)
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• cauda epididymides contain few or no mature spermatozoa in the lumen
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• cauda epididymides are relatively transparent and contain fewer spermatozoa than those in heterozygous mice
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endocrine/exocrine glands
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• testes display atrophy of the seminiferous tubules; the median number of tubules per visual field is 3.8 times greater than in wild-type testes
• median thickness of the tubule walls is 1.4-fold larger as determined by alpha-smooth muscle actin (alpha-SMA) staining (a marker of peritubular myoid cells), and 1.75 times larger as determined by CD34 staining (a marker of telocytes)
|
|
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• testes show disrupted distribution of alpha-SMA-positive peritubular myoid cells (PTMCs)
|
|
|
• at 3- to 16-weeks of age, the median number of Sox9-positive Sertoli cells per visual field is markedly increased
• when normalized by the number of seminiferous tubules, the number of Sox9-positive Sertoli cells is 1.5 times higher than in wild-type controls
• moreover, the number of Sox9-positive Sertoli cells per seminiferous tubule is increased by 1.3 times
|
|
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• seminiferous tubules show a significantly smaller cross-sectional area than wild-type tubules
|
|
|
• testicular tissue shows an expanded interstitial area mainly due to an increase in Leydig cells: the median area of interstitium per visual field of thin testicular tissue sections is significantly greater than that in wild-type controls
• distribution of telocytes (an important component of testicular interstitium) is disrupted, as visualized by CD34 expression around the seminiferous tubules
• median fluorescent signal of NR5A1 (nuclear receptor subfamily 5, group A, member 1, aka Ad4BP) in the testicular interstitium is 1.9-fold higher than in wild-type testes
|
|
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• at 3- to 16-weeks of age, Leydig cell number is increased within the expanded interstitium; the median number of Ad4BP-expressing Leydig cells per visual field is increased by >7.2-fold
• when normalized by the number of seminiferous tubules, the number of Leydig cells is increased by 1.9 times
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small testis
(
J:360728
)
|
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• 3- to 16-week-old males exhibit strikingly smaller testes than heterozygous mice
|
|
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• testes display atrophy of the seminiferous tubules
|
|
|
• testosterone synthesis is significantly increased in the testes, as shown by upregulation of genes involved in the testosterone synthesis pathway (Hsd17b3, Hsd3b1, Cyp11a1, and Cyp17a1)
• at 13-16 weeks of age, immunofluorescence staining of seminiferous tubule sections shows that the median signal intensity of Cyp17a1 is 3.46-fold lower at the single-cell level, whereas that of Hsd3b1 is significantly higher than in wild-type samples, suggesting that changes in testosterone levels produce different feedback effects on steroidogenic enzymes
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homeostasis/metabolism
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• at 13-16 weeks of age, immunofluorescence staining of seminiferous tubule sections shows a significantly increased gammaH2A.X signal intensity in Ad4BP-positive cells, indicating DNA damage associated with aging in Leydig cells
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• amount of 17alpha-hydroxyprogesterone and androstenedione (A4) is significantly increased in testes
• serum 17alpha-hydroxyprogesterone and pregnenolone levels are not significantly altered whereas serum androstenedione (A4) levels are undetectable
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• amount of progesterone is significantly increased in testes
• however, serum progesterone levels are relatively normal
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• amount of testosterone is significantly increased in testes
• however, serum testosterone levels are relatively normal, suggesting that large amounts of testosterone are consumed in the testes
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cellular
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• at 3- to 16-weeks of age, the median number of cells positive for TRA98 (a germ cell marker) is decreased
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azoospermia
(
J:360728
)
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• cauda epididymides contain few or no mature spermatozoa in the lumen
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• at 13-16 weeks of age, immunofluorescence staining of testes cross-sections shows a significantly higher signal intensity of senescence-associated beta-galactosidase (SA-beta-gal) per cell than in wild-type sections; at least 80% of SA-beta-gal signals detected in seminiferous tubule sections are consistent with Ad4BP-positive Leydig cells
• expression levels of senescence marker genes Cdkn1a and Cdkn2a are increased in the testes
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• at 13-16 weeks of age, immunofluorescence staining of seminiferous tubule sections shows a significantly increased gammaH2A.X signal intensity in Ad4BP-positive cells, indicating DNA damage associated with aging in Leydig cells
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• at 13-16 weeks of age, Leydig cells with increased testosterone synthesis show oxidative stress
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