Analysis Tools
reproductive system
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• females treated with estrogen at P21 and P22 (to increase Ltf-icre activity) show no defects in endometrial gland morphology or stromal cell compartments in the uterus at 16 weeks of age
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• females failed to produce any litters in month 5 or 6 of the breeding trial, indicating a gradual decline in fertility
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• at 6.5 dpc, the pregnancy rate is significantly lower than that in control females (12.5% versus 88.9%, respectively)
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• at 5.5 dpc, the extent of decidual development and decidual pSMAD1/5 expression are reduced in the implantation sites
• after induction of artificial decidualization, the ratio of the decidual to non-decidual uterine horn weight is significantly lower than that in controls, indicating defective stromal cell decidualization
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• at 4.5 dpc, unattached blastocysts are detected in the uterus
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• delayed embryo implantation appears to cause a subsequent cascade of defects that results in early pregnancy losses
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• at 4.5 dpc, females show a wide range of implantation defects, including loosely attached/floating blastocysts, decreased PTGS2 (aka COX2) expression, FOXO1 cytoplasmic mislocalization, and retained PR expression in the luminal uterine epithelium
• ~50% of females exhibit no implantation sites at 4.5 dpc, as detected by blue dye injection
• at 5.5 dpc, implantation sites show various morphological and molecular defects
• at 6.5 dpc, the number of implantation sites is decreased, and the few sites observed are smaller, appear to be growth restricted, and show reduced decidual development
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• at 3.5 dpc, the luminal uterine epithelium continues to proliferate and shows prominent Ki67 staining, increased MUC1 expression and enhanced E2-response, indicating a non-receptive state
• defective expression of various histological and molecular markers of endometrial receptivity is observed at 4.5 dpc
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• females failed to deliver any pups after the third month of the 6-mo fertility trial
• 4 of 7 females lost the ability to produce pups after the first litter
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• when 6-wk-old females (pretreated with estrogen at P21 and P22 to increase Ltf-icre activity) are mated with wild-type males, the total number of cumulative pups obtained over a 6-mo fertility trial is significantly lower than that in controls (35 versus 201 pups, respectively), indicating severe subfertility
• over the course of the trial, the number of pups per female is significantly lower than that in control females (5.13 +/- 3.56 versus 29.13 +/- 9.15 pups/female, respectively)
• however, the number of blastocysts collected at 3.5 dpc is not altered, indicating normal ovarian and oviductal function
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• over the course of a 6-mo fertility trial, number of pups per litter is significantly lower than that in control females (2.85 +/- 1.86 versus 6.61 +/- 1.55 pups/litter, respectively)
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embryo
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• endometrial receptivity and implantation defects result in impaired decidual and embryonic development at 5.5 dpc and 6.5 dpc
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• at 5.5 dpc, the extent of decidual development and decidual pSMAD1/5 expression are reduced in the implantation sites
• after induction of artificial decidualization, the ratio of the decidual to non-decidual uterine horn weight is significantly lower than that in controls, indicating defective stromal cell decidualization
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mortality/aging
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• females failed to produce any litters in month 5 or 6 of the breeding trial, indicating a gradual decline in fertility
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