growth/size/body
• homozygous mutants are smaller than wild-type mice
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reproductive system
|
• sperm numbers are reduced in mature male mutants
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|
• cells arrest in meiotic prophase stage/pachytene spermatocyte stage resulting in an increase in the ratio of stage X to stage XII tubules
• by about P31 some of the germ cells complete meiosis and round spermatids are now seen almost 9 days later compared to wild-type littermates
• multinucleated giant cells, degenerating pachytene spermatocytes, and necrotic and apoptotic primary spermatocytes are also seen
|
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• necrotic tubules are seen
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• testis weight but not overall size is reduced
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• after PMSG treatment with or without addition of hCG, LHR mRNA expression is lower than that in wild-type ovaries
• decreased LHR expression results in reduced serum estradiol and progesterone via reduced expression of key enzymes involved in steroidogenesis
|
|
• following treatment with PMSG for 48 h, TUNEL staining revealed intensive granulosa cell apoptosis in many preantral and early antral follicles, whereas little TUNEL staining is observed in wild-type controls
• percentages of atretic follicles containing 5 or more apoptotic granulosa cells are significantly greater than in wild-type ovaries
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• at 12-22 weeks of age, the weights of internal female genital organs (bilateral ovaries, uterus, and vagina) are significantly reduced during the estrous stage and diestrous stage
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• after stimulation with PMSG + hCG treatment, females produce significantly smaller corpora lutea than wild-type controls
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• during the diestrous or estrous stage, adult ovaries contain fewer/absent corpora lutea than wild-type ovaries
• after stimulation with PMSG + hCG treatment, females produce significantly fewer corpora lutea than wild-type controls
|
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• during the diestrous or estrous stage, adult ovaries contain fewer/absent preovulatory follicles than wild-type ovaries; however, all stages of primary, preantral, and antral follicles are present and histologically normal
• after stimulation with PMSG treatment, females produce significantly fewer preovulatory follicles than wild-type controls
|
|
• after stimulation with PMSG treatment, ovaries contain more atretic follicles than similarly treated wild-type ovaries
|
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• primary cause of female subfertility is defective folliculogenesis; follicular development is not affected until the late antral stage
• fewer follicles reach the preovulatory stage, and the remaining follicles are gradually eliminated via the apoptotic process
• however, both serum LH and FSH concentrations are relatively normal
|
small ovary
(
J:133000
)
|
• adult ovary sizes are smaller than in wild-type females
• after stimulation with PMSG treatment, ovaries remain smaller than wild-type ovaries
|
small uterus
(
J:133000
)
|
|
small vagina
(
J:133000
)
|
|
|
• vaginal opening is delayed, with no vaginal opening observed at 5 weeks of age
|
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• age of first ovulation is delayed relative to that in wild-type females (51.2 +/- 5.8 days versus 37.6 +/- 1.81 days)
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• following induction of superovulation with exogenous gonadotropins, immature 26-day-old females produce significantly fewer oocytes than superovulated wild-type or heterozygous controls
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• females exhibit prolonged and irregular estrous cycles
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• percentage of days spent in diestrus is significantly increased relative to that in wild-type females (67.4 +/- 9.93% versus 41.2 +/- 5.21%)
|
short estrus
(
J:133000
)
|
|
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• after 12 weeks of continuous mating with fertile male mice, 10- to 12-week-old females show subfertility with a significant reduction in litter size and number of litters per female
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• when mated with fertile male mice, females produce a litter size of 5.25 +/- 1.66 pups/litter relative to 8.95 +/- 1.39 and 9.15 +/- 1.34 pups/litter for wild-type and heterozygous controls, respectively
|
|
• only 1 out of 5 homozygous mutant males sired a litter in the span of 4 months
|
cellular
|
• sperm numbers are reduced in mature male mutants
|
|
• cells arrest in meiotic prophase stage/pachytene spermatocyte stage resulting in an increase in the ratio of stage X to stage XII tubules
• by about P31 some of the germ cells complete meiosis and round spermatids are now seen almost 9 days later compared to wild-type littermates
• multinucleated giant cells, degenerating pachytene spermatocytes, and necrotic and apoptotic primary spermatocytes are also seen
|
|
• following treatment with PMSG for 48 h, TUNEL staining revealed intensive granulosa cell apoptosis in many preantral and early antral follicles, whereas little TUNEL staining is observed in wild-type controls
• percentages of atretic follicles containing 5 or more apoptotic granulosa cells are significantly greater than in wild-type ovaries
|
homeostasis/metabolism
|
• after PMSG stimulation for 48 h with an additional 22 h of hCG, serum estradiol concentrations are significantly lower than those in wild-type controls
|
|
• after PMSG stimulation for 48 h with an additional 22 h of hCG, serum progesterone concentrations are significantly lower than those in wild-type controls
|
hematopoietic system
• at E13.5, betaH1 globin silencing is significantly delayed
• however, epsilon-y and adult beta-globin genes are unaffected
|
endocrine/exocrine glands
|
• after stimulation with PMSG + hCG treatment, females produce significantly smaller corpora lutea than wild-type controls
|
|
• during the diestrous or estrous stage, adult ovaries contain fewer/absent corpora lutea than wild-type ovaries
• after stimulation with PMSG + hCG treatment, females produce significantly fewer corpora lutea than wild-type controls
|
|
• during the diestrous or estrous stage, adult ovaries contain fewer/absent preovulatory follicles than wild-type ovaries; however, all stages of primary, preantral, and antral follicles are present and histologically normal
• after stimulation with PMSG treatment, females produce significantly fewer preovulatory follicles than wild-type controls
|
|
• after stimulation with PMSG treatment, ovaries contain more atretic follicles than similarly treated wild-type ovaries
|
|
• primary cause of female subfertility is defective folliculogenesis; follicular development is not affected until the late antral stage
• fewer follicles reach the preovulatory stage, and the remaining follicles are gradually eliminated via the apoptotic process
• however, both serum LH and FSH concentrations are relatively normal
|
small ovary
(
J:133000
)
|
• adult ovary sizes are smaller than in wild-type females
• after stimulation with PMSG treatment, ovaries remain smaller than wild-type ovaries
|
|
• necrotic tubules are seen
|
|
• testis weight but not overall size is reduced
|
|
• after PMSG treatment with or without addition of hCG, LHR mRNA expression is lower than that in wild-type ovaries
• decreased LHR expression results in reduced serum estradiol and progesterone via reduced expression of key enzymes involved in steroidogenesis
|
|
• following treatment with PMSG for 48 h, TUNEL staining revealed intensive granulosa cell apoptosis in many preantral and early antral follicles, whereas little TUNEL staining is observed in wild-type controls
• percentages of atretic follicles containing 5 or more apoptotic granulosa cells are significantly greater than in wild-type ovaries
|