All Phenotypes Kat8<tm1Thl> MGI Mouse

abnormal oogenesis ( J:242000 )

• pregnant mare serum gonadotropin (PMSG)-primed females show abnormal oogenesis at 8 weeks of age

abnormal oocyte morphology ( J:242000 )

• after PMSG priming, germinal vesicle (GV) stage oocytes are much smaller (mean diameter 63.7 um versus 81.4 um in wild-types oocytes) and show abnormal morphology, including cytoplasmic granulation, shrinkage and an irregular shape

• at 3 weeks of age, the ratio of oocytes with >5 gamma-H2AX foci is ~56.8% versus ~14.6% in wild-type oocytes, indicating severe DNA damage (double-strand breaks)

• oocytes from 2-week-old females show abnormal heterochromatin configurations: >55% of heterochromatin regions are abnormally shaped, unlike in wild-type oocytes where >80% of heterochromatin regions display a normal oval or round shape

• NAC-treated oocytes show a 58.7% reduction in double-strand breaks relative to PBS-treated oocytes

decreased oocyte number ( J:242000 )

• after PMSG priming, only ~20 full-grown germinal vesicle (GV) stage oocytes are recovered per female versus ~50 oocytes per wild-type control

• following superovulation with PMSG and HCG, more metaphase II (MII) oocytes are recovered from NAC-treated mice than from PBS-treated mice at 3 weeks of age

abnormal female germ cell physiology ( J:242000 )

• oocytes from 2-week-old females show decreased antioxidant gene expression and increased reactive oxygen species (ROS) levels

• following daily i.p. injection of antioxidant N-acetylcysteine (NAC) for 7 days, NAC-treated oocytes show a 67.1% reduction in ROS levels relative to PBS-treated oocytes

increased female germ cell apoptosis ( J:242000 )

• TUNEL assays revealed significant oocyte apoptosis at 3 weeks of age (~17.2% versus ~5.7% in wild-type oocytes)

• following daily i.p. injection of antioxidant N-acetylcysteine (NAC) for 7 days, NAC-treated oocytes show a 56.1% reduction in TUNEL+ cells

increased atretic ovarian follicle number ( J:242000 )

• ovaries contain 2-fold more atretic follicles at 3 weeks of age

• NAC-treated ovaries show a 54.7% reduction in the number of atretic follicles relative to PBS-treated ovaries

impaired ovarian folliculogenesis ( J:242000 )

• ovaries contain 50.4%, 49.6% and 78.7% fewer secondary, preantral and antral follicles at 3 weeks of age

• ovarian follicle development arrests in the secondary and preantral follicle stage; however, granulosa cell proliferation is normal in secondary and preantral follicles at 2 weeks of age

• TUNEL assays and gamma-H2AX immunostaining confirmed that oocytes undergoing apoptosis or exhibiting severe DNA damage are localized in secondary and preantral follicles, but not in primordial or primary follicles

• NAC-treated ovaries show a 60.0%, 83.8% and 224.2% increase in the number of secondary, preantral and antral follicles, respectively, indicating partial rescue of follicular development and survival

small ovary ( J:242000 )

• ovaries are markedly smaller at 8 weeks of age

• following daily i.p. injection of antioxidant N-acetylcysteine (NAC) for 7 days, 3-week-old NAC-treated mice have larger ovaries than PBS-treated mice; however, NAC treatment does not fully restore ovaries to wild-type size

decreased ovary weight ( J:242000 )

• females show a 77.4% reduction in ovary weight to body weight ratio at 8 weeks of age

• 3-week-old NAC-treated mice show a higher ovary weight to body weight ratio than PBS-treated mice

female infertility ( J:242000 )

• 8- to 10-week-old females fail to produce offspring during a 6-month mating period with wild-type males