Analysis Tools
reproductive system
 N |
• males are fertile and able to sire multiple litters at a normal frequency through 12 weeks of age
|
 |
• many ovulated oocytes are not competent, suggesting that oocyte maturation is disrupted
|
|
|
• after normal ovulation, 83% of oocytes collected from the oviducts during estrus are atretic (degenerated) relative to only 4% in control females
• after superovulation, the number of atretic oocytes is 7-fold higher than that in control females
• however, the number of healthy oocytes is not significantly altered
|
|
|
• by 5 months of age, 100% of males show complete or partial loss of germ cells and tubules with only Sertoli cells
|
|
|
• Dietrick's staining showed significantly fewer primordial follicles at 12 weeks of age; immunofluorescence staining with oocyte-specific marker MVH confirmed that fewer primordial follicles are present in the cortex
• decrease in primordial follicles is more severe at 24 weeks of age
• however, number of total follicles and primordial follicles is normal at 6 weeks of age
|
|
|
• number of atretic follicles is normal at 6 weeks but significantly increased at 12 weeks of age
• a non-significant trend towards a higher atretic follicle number is noted at 24 weeks
|
|
|
• ovarian folliculogenesis is disrupted
|
|
|
• testicular junction integrity is compromised
|
|
|
• adult Sertoli cells show disruption of cell cycle quiescence and thus increased proliferation in mice older than 4 months of age
|
|
|
• by 5 months of age, 100% of males show complete or partial loss of germ cells and tubules with only Sertoli cells
|
|
|
• 12 week old, but not 4 week old, testes show vacuolization of seminiferous epithelium
|
|
|
• Sertoli cells show disruption of the spoke-like pattern of microtubules and loss of apical extensions, and disruption of actin filament arrangement, indicating disruption of polarity
|
small testis
(
J:187754
)
|
|
• small testis in adult males
|
|
|
• decreased testis weight in adult males
|
|
|
• at estrus, ovarian mRNA levels of Muc1 (mucin 1, transmembrane) are reduced by 50% whereas mRNA levels of Hif1a (hypoxia inducible factor 1, alpha subunit) are increased by 50% relative to control ovaries
|
|
|
• females show premature ovarian insufficiency, possibly related to increased time spent in estrus
|
|
|
• secretory epithelial cell disorganization and dysplasia is observed in the proximal portion of the oviduct, occluding the lumen
• occlusion of the proximal oviduct is likely to inhibit proper transit of embryos through the oviduct, contributing to female infertility
• however, ciliated and secretory epithelial cells of the distal oviduct appear intact
|
|
|
• at E3.5 after natural mating, bilateral swelling of the ampullas resembling hydrosalpinges is observed in all females due to occlusion of the proximal oviduct, whereas no swelling is seen in controls females
• upon puncture, blastocysts and many degenerated bodies (~75%) are released from the swollen ampulla
|
|
|
• endometrial epithelial cells continue to proliferate in E4.5 uteri, unlike in control uteri
• however, no evidence of endometrial cancer is observed
|
|
|
• females exhibit significant myometrial hyperplasia mice as they age
|
|
|
• immature round germ cells are seen in the epididymides whereas only mature elongated germ cells are seen in controls
|
|
|
• duration of diestrus is shortened
• however, serum 17beta-estradiol (E2) progesterone (P4) levels at diestrus are normal
|
|
|
• duration of the estrous stage is prolonged
• however, serum 17beta-estradiol (E2) progesterone (P4) levels at estrus are normal
|
|
|
• at E4.5 after natural mating, no implantation sites are detected, unlike in controls females
• endometrial epithelial cells continue to proliferate and Muc1 mRNA expression remains elevated in E4.5 uteri (with no changes in progesterone receptor mRNA levels), suggesting that Muc1 continued expression may contribute to failure of implantation
• transfer of E3.5 wild-type embryos into uteri of pseudopregnant mutant female mice fails, with no evidence of embryo implantation sites 4-6 days after transfer
|
|
|
• females mated with control males of known fertility fail to produce any offspring over a 5-month breeding period
• however, seminal plugs are observed suggesting normal female mating behavior
|
cellular
|
|
• many ovulated oocytes are not competent, suggesting that oocyte maturation is disrupted
|
|
|
• after normal ovulation, 83% of oocytes collected from the oviducts during estrus are atretic (degenerated) relative to only 4% in control females
• after superovulation, the number of atretic oocytes is 7-fold higher than that in control females
• however, the number of healthy oocytes is not significantly altered
|
|
|
• by 5 months of age, 100% of males show complete or partial loss of germ cells and tubules with only Sertoli cells
|
|
|
• adult Sertoli cells show disruption of cell cycle quiescence and thus increased proliferation in mice older than 4 months of age
|
mortality/aging
|
|
• females show premature ovarian insufficiency, possibly related to increased time spent in estrus
|
embryo
|
|
• after natural mating, more E2.5 embryos are detected in the oviducts but 75% of them are degenerated embryos
• at E3.5 after natural mating, no blastocysts are detected in the uteri after flushing, unlike in control females
• however, the absolute number of good-quality embryos found in the ampullas is normal at both E2.5 and E3.5, suggesting that good-quality oocytes can develop into blastocysts
|
endocrine/exocrine glands
|
|
• Dietrick's staining showed significantly fewer primordial follicles at 12 weeks of age; immunofluorescence staining with oocyte-specific marker MVH confirmed that fewer primordial follicles are present in the cortex
• decrease in primordial follicles is more severe at 24 weeks of age
• however, number of total follicles and primordial follicles is normal at 6 weeks of age
|
|
|
• number of atretic follicles is normal at 6 weeks but significantly increased at 12 weeks of age
• a non-significant trend towards a higher atretic follicle number is noted at 24 weeks
|
|
|
• ovarian folliculogenesis is disrupted
|
|
|
• testicular junction integrity is compromised
|
|
|
• adult Sertoli cells show disruption of cell cycle quiescence and thus increased proliferation in mice older than 4 months of age
|
|
|
• by 5 months of age, 100% of males show complete or partial loss of germ cells and tubules with only Sertoli cells
|
|
|
• 12 week old, but not 4 week old, testes show vacuolization of seminiferous epithelium
|
|
|
• Sertoli cells show disruption of the spoke-like pattern of microtubules and loss of apical extensions, and disruption of actin filament arrangement, indicating disruption of polarity
|
small testis
(
J:187754
)
|
|
• small testis in adult males
|
|
|
• decreased testis weight in adult males
|
|
|
• at estrus, ovarian mRNA levels of Muc1 (mucin 1, transmembrane) are reduced by 50% whereas mRNA levels of Hif1a (hypoxia inducible factor 1, alpha subunit) are increased by 50% relative to control ovaries
|
|
|
• females show premature ovarian insufficiency, possibly related to increased time spent in estrus
|
neoplasm
|
N |
• no evidence of endometrial or ovarian cancer is observed
(J:181774)
|
|
N |
• testicular tumors are not observed up to 10 months of age
(J:187754)
|
