Analysis Tools
reproductive system
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• homozygous mutant females show normal fertility
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• at P60, H&E staining revealed reduced numbers of mature spermatozoa in the seminiferous tubules
• at P35, the number of elongated spermatids and mature sperm is decreased in the seminiferous tubules
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small testis
(
J:333195
)
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• homozygous mutant testes are smaller than wild-type testes at P21-P35
• however, gonad-somatic index, overall testis appearance and histology are normal at P3-P14 and at P120
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• mutant testes show significantly increased protein levels of mitochondrial uncoupling protein 2 (UCP2), involved in regulating the glycolysis pathway and glucose-derived pyruvate levels
• pyruvate, the final product of cytosolic glycolysis, is slightly increased in mutant testes
• ATP levels are slightly decreased in mutant testes
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• at P35, TUNEL analysis showed a slightly increased apoptosis level within the seminiferous tubules
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• a delay in the first wave of spermatogenesis is observed
• at P21-P35, mutant seminiferous tubules show a reduced number of spermatogenic cells
• exfoliated spermatogenic cells are observed in the testis at P37
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• at P37, P60 and P120, homozygous mutant males show a significant reduction in cauda epididymidal sperm count
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• spermiogenesis is mildly impaired; differentiation of mutant round spermatids is delayed at P21
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• exfoliated spermatogenic cells are observed in the caput epididymis at P37
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• on day 5.5 of pregnancy, uteri of female mice mated with homozygous mutant males show a significantly lower number of implantation sites than control uteri
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• matings of adult homozygous mutant males with wild-type or homozygous mutant females produce an average litter size of 4.56 and 3.87, respectively
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• adult homozygous mutant male mice exhibit reduced fertility
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• male subfertility is due to impaired sperm fertilizing ability
• impaired fertilization capacity is partially caused by weakened sperm-egg interactions
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• in vivo fertilization rate, expressed as the % of 2-cell embryos recovered from the oviducts of superovulated female mice plugged with homozygous mutant males, is 23.69% versus 75.57% in wild-type males
• however, in vitro fertilization rate is normal when oocyte-cumulus complexes are used
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• mutant sperm show a slightly decreased ability to bind to the ZP and egg plasma membrane
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• mutant sperm show significantly increased protein levels of mitochondrial uncoupling protein 2 (UCP2)
• when glucose is used as the sole substrate, total pyruvate levels are significantly increased in mutant cauda epididymal sperm, indicating enhanced glycolysis
• when pyruvate is used as the sole metabolic substrate (glucose-free), the amount of pyruvate consumed by mutant sperm is significantly higher than that consumed by wild-type sperm
• when sodium oxamate (OA), a competitive inhibitor of LDH activity, is used to block the conversion of pyruvate to lactate, the amount of pyruvate consumed by mutant sperm is similar to that of wild-type sperm, indicating elevated anaerobic glycolytic pathway
• ATP levels are significantly reduced in mutant epididymal spermatozoa (0 min) relative to those in wild-type sperm
• ATP levels are increased after 30 min of incubation but are significantly decreased after treatment with OA for 30 min
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• after 15 min of incubation in HTF culture medium, the numbers of progressively motile sperm, characterized by fast rectilinear motility and hyperactive curvilinear motility, are significantly reduced
• however, no differences in the proportions of total motile sperm are observed
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• mutant spermatozoa exhibit decreased sperm motility due to defective ATP synthesis
• however, the structure of mutant spermatozoa is normal
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• following stimulation with progesterone, the % of mutant sperm with acrosome reactions is significantly lower than that in wild-type controls
• however, acrosin activity, assayed using N-benzoyl-DL-arginine- p- nitroanilide (BAPNA) as a substrate, is normal
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cellular
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• at P60, H&E staining revealed reduced numbers of mature spermatozoa in the seminiferous tubules
• at P35, the number of elongated spermatids and mature sperm is decreased in the seminiferous tubules
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• at P37, P60 and P120, homozygous mutant males show a significant reduction in cauda epididymidal sperm count
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• at P35, TUNEL analysis showed a slightly increased apoptosis level within the seminiferous tubules
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• after 15 min of incubation in HTF culture medium, the numbers of progressively motile sperm, characterized by fast rectilinear motility and hyperactive curvilinear motility, are significantly reduced
• however, no differences in the proportions of total motile sperm are observed
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• mutant spermatozoa exhibit decreased sperm motility due to defective ATP synthesis
• however, the structure of mutant spermatozoa is normal
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• mutant spermatozoa show significantly lower basal and maximal oxygen consumption than wild-type spermatozoa, suggesting defects in mitochondrial respiration
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• mutant sperm exhibit oxidative phosphorylation deficiency and are highly dependent on increased anaerobic glycolysis to compensate for ATP demands
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endocrine/exocrine glands
small testis
(
J:333195
)
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• homozygous mutant testes are smaller than wild-type testes at P21-P35
• however, gonad-somatic index, overall testis appearance and histology are normal at P3-P14 and at P120
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• mutant testes show significantly increased protein levels of mitochondrial uncoupling protein 2 (UCP2), involved in regulating the glycolysis pathway and glucose-derived pyruvate levels
• pyruvate, the final product of cytosolic glycolysis, is slightly increased in mutant testes
• ATP levels are slightly decreased in mutant testes
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• at P35, TUNEL analysis showed a slightly increased apoptosis level within the seminiferous tubules
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