reproductive system
|
• adult males show no differences in mounting and copulatory activity or in testicular descent and masculinization of internal reproductive organs (seminal vesicles and prostate) relative to control littermates
|
|
• at P60, numerous exfoliated germ cells are detected in the lumen of mutant epididymal ducts
|
|
• at P60, mutant male germ cells are severely disorganized and reduced in number
• by 6 months of age, the few remaining tubes are almost completely devoid of germ cells
|
azoospermia
(
J:145178
)
|
• at P60, mutant males show complete absence of mature spermatozoa in testes and epididymal ducts
|
|
• at P42, round spermatids are severely reduced in number while elongated spermatids are entirely absent in mutant testes
|
|
• significant male germ cell apoptosis is noted at P15 and P21
• by P42, mutant male germ cells exhibit extensive apoptosis
|
|
• a 1.25-, 1.5-, and 2.6-fold increase in Sertoli cell proliferation is observed at P0, P5, and P15, respectively, suggesting delayed Sertoli cell maturation
|
|
• at P60, the mutant seminiferous epithelium appears disorganized
|
|
• as early as P5, mutant males display Sertoli cell nuclear mislocalization with almost complete absence of lumen
• at P15, mutant Sertoli cell nuclei display an abnormal circular rather than flattened triangular shape
• a 1.25-, 1.5-, and 2.6-fold increase in Sertoli cell proliferation is observed at P0, P5, and P15, respectively, suggesting delayed Sertoli cell maturation
• significant Sertoli cell apoptosis is noted at P5; however, by P21, apoptotic cells are almost exclusively germ cells
• by 3 months of age, obvious defects in Sertoli cell cyto-architecture and polarity are observed
|
|
• as early as P5, mutant Sertoli cell nuclei are mislocalized in the center of seminiferous tubes instead of the periphery
|
|
• at P60, mutant seminiferous tubules are reduced in diameter and devoid of lumen
|
|
• as early as P5, numerous pycnotic cells are detected within mutant tubes
• at P42, almost all mutant tubes have become severely vacuolized; however, a few less severely affected tubes display a lumen
• by 3 months of age, most seminiferous tubules have degenerated into Sertoli-cell-only tubes with a severely impaired Sertoli cell morphology
|
|
• Leydig cell hyperplasia is already noted at P5, persists throughout adulthood, and becomes massive by 6 months of age
• however, no significant differences in testicular testosterone levels are observed from P0 to P60
|
small testis
(
J:145178
)
|
• at P15 and P60, mutant testes show a 80% and 90% reduction in size, respectively, relative to control testes
• by 6 months of age, mutant testis size is only 5% of that in control littermates
|
|
• at P60, mutant males show a 90% reduction in testis weight relative to control littermates
|
|
• severe testicular degeneration is noted at P60 and worsens upon aging
• by 6 months of age, mutant testes have degenerated into a mass of interstitial cells containing rare remaining tubes
|
|
• at P60, mutant males show severe spermatogenic defects including vacuolization, Sertoli-cell-only tubes, tubes with spermatogenic arrest at an early post-meiotic stage, and disorganization of the seminiferous epithelium
|
|
• mutant males fail to produce any offspring during a 6-month mating period with wild-type C57BL/6J females
|
endocrine/exocrine glands
|
• a 1.25-, 1.5-, and 2.6-fold increase in Sertoli cell proliferation is observed at P0, P5, and P15, respectively, suggesting delayed Sertoli cell maturation
|
|
• at P60, the mutant seminiferous epithelium appears disorganized
|
|
• as early as P5, mutant males display Sertoli cell nuclear mislocalization with almost complete absence of lumen
• at P15, mutant Sertoli cell nuclei display an abnormal circular rather than flattened triangular shape
• a 1.25-, 1.5-, and 2.6-fold increase in Sertoli cell proliferation is observed at P0, P5, and P15, respectively, suggesting delayed Sertoli cell maturation
• significant Sertoli cell apoptosis is noted at P5; however, by P21, apoptotic cells are almost exclusively germ cells
• by 3 months of age, obvious defects in Sertoli cell cyto-architecture and polarity are observed
|
|
• as early as P5, mutant Sertoli cell nuclei are mislocalized in the center of seminiferous tubes instead of the periphery
|
|
• at P60, mutant seminiferous tubules are reduced in diameter and devoid of lumen
|
|
• as early as P5, numerous pycnotic cells are detected within mutant tubes
• at P42, almost all mutant tubes have become severely vacuolized; however, a few less severely affected tubes display a lumen
• by 3 months of age, most seminiferous tubules have degenerated into Sertoli-cell-only tubes with a severely impaired Sertoli cell morphology
|
|
• Leydig cell hyperplasia is already noted at P5, persists throughout adulthood, and becomes massive by 6 months of age
• however, no significant differences in testicular testosterone levels are observed from P0 to P60
|
small testis
(
J:145178
)
|
• at P15 and P60, mutant testes show a 80% and 90% reduction in size, respectively, relative to control testes
• by 6 months of age, mutant testis size is only 5% of that in control littermates
|
|
• at P60, mutant males show a 90% reduction in testis weight relative to control littermates
|
|
• severe testicular degeneration is noted at P60 and worsens upon aging
• by 6 months of age, mutant testes have degenerated into a mass of interstitial cells containing rare remaining tubes
|
cellular
|
• at P60, numerous exfoliated germ cells are detected in the lumen of mutant epididymal ducts
|
|
• at P60, mutant male germ cells are severely disorganized and reduced in number
• by 6 months of age, the few remaining tubes are almost completely devoid of germ cells
|
azoospermia
(
J:145178
)
|
• at P60, mutant males show complete absence of mature spermatozoa in testes and epididymal ducts
|
|
• at P42, round spermatids are severely reduced in number while elongated spermatids are entirely absent in mutant testes
|
|
• significant male germ cell apoptosis is noted at P15 and P21
• by P42, mutant male germ cells exhibit extensive apoptosis
|
|
• a 1.25-, 1.5-, and 2.6-fold increase in Sertoli cell proliferation is observed at P0, P5, and P15, respectively, suggesting delayed Sertoli cell maturation
|