reproductive system
• progressive loss of meitotic cells and spermatids with age
(J:156653)
• however, the earliest spermatogonia are retained
(J:156653)
• significant loss of male germ cells at all stages of meiosis and differentiation by 14 weeks of age
(J:171525)
|
• females exhibit multiple defects during oocyte development, including delays in meiotic progression and lagging chromosomes during metaphase II
• however, cultured germinal vesicle (GV) oocytes obtained from antral follicles show no gross defects in histone H2A Thr120 and histone H3 Ser10 phosphorylation
|
• in vitro, many oocytes obtained from the ampulla of superovulated females fail to reach MII arrest
• only 15.6% of GV stage oocytes reach the "parachute" stage versus 49.1% in wild-type females; however, normal numbers of oocytes are found at later stages (prometaphase and metaphase I)
• only 22.5% of GV stage oocytes ultimately reach metaphase II versus 54.5% in wild-type females
• 42.9% of those GV stage oocytes that reach metaphase II exhibit lagging chromosomes versus 2.7% in wild-type females; as a result, less than 13% of oocytes reach metaphase II properly
• however, spindle formation and spindle length remain normal and the overall chromosome number is unaffected
|
• in vitro, only 27.9% of GV stage oocytes obtained from antral follicles of superovulated females show polar body extrusion versus 59.9% in wild-type females; 67.7% progress through germinal vesicle breakdown (GVBD) but fail to extrude a polar body versus only 39.2% in wild-type females, indicating meiotic delays
|
• as early as 6 weeks of age, a striking loss of cellular density is seen in many tubules with only Sertoli cells present
• by 11 weeks of age all tubules contain only Sertoli cells
|
(J:156653)
• marked loss/degeneration of the seminiferous tubular epithelium by 14 weeks of age
(J:171525)
|
small testis
(
J:156653
)
• decrease in the size of the testis in post pubescent mice, although the overall body sizes of all mice are comparable
|
• testis weight is significantly decreased at all ages examined between 6-8 and >12 weeks of age
|
• all males are fertile at the onset of sexual maturity but become sterile by 10 weeks of age
|
• largely devoid of GCNA+ cells in tubules, a marker of spermatogonial stem cells, mitotic spermatogonia, and cells in the prediplotene stages of meiosis I
(J:156653)
• PCNA + cells, a marker of proliferating type A and B spermatogonia, are present at 4 weeks but by 14 weeks, 90% of tubules devoid
(J:156653)
• adult mice are devoid of KIT+, an early spermatogonial differentiation marker, cells
(J:156653)
• progressive reduction of all stages of spermatogenesis within testes, starting at 10 weeks of age
(J:171525)
• no meiotic arrest or defects in synaptonemal complex formation are observed
(J:171525)
|
azoospermia
(
J:156653
)
|
• progressive loss of spermatids with age
|
• progressive loss of proliferating spermatogonia
|
• at 6 weeks of age only 20% of lumens have sperm
• at 12 weeks of age, the lumens of the epididymal tubules are devoid of sperm
|
(J:156653)
• females fail to produce litters or show any signs of pregnancy
(J:171525)
• however, deposition of seminal fluid is always observed, and ovaries contain all stages of folliculogenesis (including corpora lutea) indicating successful ovulation
(J:171525)
|
• in fertility tests, only 1 of 9 males produce a single litter, all of the other males fail to produce any litters
(J:156653)
• all males are sterile by 10 weeks of age; males never sire a litter after 69 days postpartum (dpp), despite continued presence of copulatory plugs
(J:171525)
|
• in vitro, most oocytes obtained from the ampulla of superovulated females show absence of maternal and paternal pronuclei and no embryonic development, indicating failure of fertilization
• some oocytes progress to the 2-cell stage but not beyond, and all oocytes degenerate after 96 hours in culture
|
cellular
• progressive loss of spermatids with age
|
• progressive loss of meitotic cells and spermatids with age
(J:156653)
• however, the earliest spermatogonia are retained
(J:156653)
• significant loss of male germ cells at all stages of meiosis and differentiation by 14 weeks of age
(J:171525)
|
azoospermia
(
J:156653
)
|
• females exhibit multiple defects during oocyte development, including delays in meiotic progression and lagging chromosomes during metaphase II
• however, cultured germinal vesicle (GV) oocytes obtained from antral follicles show no gross defects in histone H2A Thr120 and histone H3 Ser10 phosphorylation
|
• in vitro, many oocytes obtained from the ampulla of superovulated females fail to reach MII arrest
• only 15.6% of GV stage oocytes reach the "parachute" stage versus 49.1% in wild-type females; however, normal numbers of oocytes are found at later stages (prometaphase and metaphase I)
• only 22.5% of GV stage oocytes ultimately reach metaphase II versus 54.5% in wild-type females
• 42.9% of those GV stage oocytes that reach metaphase II exhibit lagging chromosomes versus 2.7% in wild-type females; as a result, less than 13% of oocytes reach metaphase II properly
• however, spindle formation and spindle length remain normal and the overall chromosome number is unaffected
|
• in vitro, only 27.9% of GV stage oocytes obtained from antral follicles of superovulated females show polar body extrusion versus 59.9% in wild-type females; 67.7% progress through germinal vesicle breakdown (GVBD) but fail to extrude a polar body versus only 39.2% in wild-type females, indicating meiotic delays
|
• progressive loss of proliferating spermatogonia
|
mortality/aging
• all males are fertile at the onset of sexual maturity but become sterile by 10 weeks of age
|
endocrine/exocrine glands
• as early as 6 weeks of age, a striking loss of cellular density is seen in many tubules with only Sertoli cells present
• by 11 weeks of age all tubules contain only Sertoli cells
|
(J:156653)
• marked loss/degeneration of the seminiferous tubular epithelium by 14 weeks of age
(J:171525)
|
small testis
(
J:156653
)
• decrease in the size of the testis in post pubescent mice, although the overall body sizes of all mice are comparable
|
• testis weight is significantly decreased at all ages examined between 6-8 and >12 weeks of age
|