reproductive system
N |
• males show no significant differences in testis weight, seminiferous tubule diameter, seminiferous epithelium morphology, expression of Sertoli and germ cell markers, total epididymal sperm count or sperm motility relative to control males
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• seminal vesicle weight is significantly reduced at P75 and P180
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• although an increase in Leydig cell numbers is observed up to ~P35, the total number of Leydig cells (Cyp11a1 positive cells) per testis is significantly reduced at all ages examined
• Leydig cell hypoplasia is accompanied by reduced testicular expression of several Leydig cell markers
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• in culture, primary Leydig cells from 50-day-old males show a drastic reduction in basal testosterone as well as severely impaired testosterone synthesis in response to stimulation with hCG (human choriogonadotropin), dibutyryl(Bt2)cAMP (a permeable cAMP analog), 22OHC (22-hydroxycholesterol) or P5 (pregnenolone)
• however, cAMP accumulation in response to hCG stimulation is normal
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• when males are paired with females of known fertility, the average number of pups/littler is significantly lower than that for control males (3.3 +/- 1.9 versus 6.5 +/- 0.6, respectively)
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• male fertility starts to decline at ~3 months of age, and by 6 months the cumulative number of pups sired by males paired with fertile females is only ~50% of that sired by control males
• at the end of the 6-month mating period, the number of litters and number of pups/litter are significantly reduced relative to controls from 5.7 +/- 0.2 to 3.8 +/- 0.6 and from 6.2 +/- 0.3 to 4.8 +/- 0.5, respectively, while the number of days between litters is increased from 27 +/- 1 to 31 +/- 1
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homeostasis/metabolism
endocrine/exocrine glands
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• seminal vesicle weight is significantly reduced at P75 and P180
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• although an increase in Leydig cell numbers is observed up to ~P35, the total number of Leydig cells (Cyp11a1 positive cells) per testis is significantly reduced at all ages examined
• Leydig cell hypoplasia is accompanied by reduced testicular expression of several Leydig cell markers
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• in culture, primary Leydig cells from 50-day-old males show a drastic reduction in basal testosterone as well as severely impaired testosterone synthesis in response to stimulation with hCG (human choriogonadotropin), dibutyryl(Bt2)cAMP (a permeable cAMP analog), 22OHC (22-hydroxycholesterol) or P5 (pregnenolone)
• however, cAMP accumulation in response to hCG stimulation is normal
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behavior/neurological
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• when males are paired with females of known fertility, the number of vaginal plugs is significantly lower than that detected with control males
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