Analysis Tools
reproductive system
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• females show no significant alterations in estrous cycles, corpora lutea numbers, or implantation sites
• males mated with wild-type females are fertile and show normal average letter size per male, cauda epididymal sperm count and testicular histology
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• at E5.5, six of 25 sectioned embryos exhibit a smaller primary decidual zone (PDZ), as indicated by Cox2+ cells surrounding the embryos
• by E13.5, females show a higher % of resorption sites than wild-type females, indicating a possible defect in decidualization or placentation
• in vitro, primary mouse endometrial stromal cells (MESCs) show a markedly lower response to decidualization stimuli, as indicated by decidual markers
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• uterus histology showed disrupted myometrial structure at the conceptus site, an increase in disarrayed collagen fibers with a loosely arranged matrix at E13.5, and discontinuous smooth muscle sheets at E13.5 and E19
• transcriptome analysis showed dysregulation of genes involved in myometrial remodeling and contractility
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• uterus histology showed a thinner myometrium during mid- and late gestation
• however, myometrial cell proliferation remains unaffected, suggesting that reduced myometrial thickness is primarily due to changes in the extracellular matrix
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• at 4 to 6 months of age, females show a significant reduction in gestational weight gain (difference in body weight between E18.5 and E0.5) relative to wild-type females
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• at 4 to 6 months of age, 86.6% of females exhibit delayed parturition with labor onset beyond E19.5 and/or elongated parturition with dystocia longer than 6 h
• however, ovarian luteolysis is normal at late gestation (E19); moreover, females show normal gestation length and labor onset at 2 months of age
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• some females give birth after E20.5 showing prolonged labor for 2 consecutive days, whereas wild-type females deliver offspring by E19.5, typically within 4 h
• nonexpulsed dead embryos are observed 48 h after the onset of labor at E21.5, resulting in a fetal demise rate greater than 30%
• however, full-term embryos are alive at E19
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• some females initiate labor on time but have difficulties in fully expelling all embryos
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• qPCR analysis showed lack of upregulation of the myometrial contraction genes Oxtr (oxytocin receptor) and Gja1 (gap junction alpha 1) but no change in Pgr (progesterone receptor) expression at late gestation (E19)
• transcriptome analysis of the myometrium identified differentially expressed genes associated with cell adhesion, extracellular matrix organization, collagen fibers, and gap junctions, suggesting that inadequate myometrial contractility results from a failure in myometrial remodeling
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• at 4 to 6 months of age, females exhibit a shift towards a subfertility phenotype
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• at 4 to 6 months of age, females show a significantly lower average litter size than wild-type females (5.6 +/- 0.5 versus 8.1 +/- 0.4 pups/litter, respectively), with about half of born pups found dead
• however, females show no change in average litter size at 2 months of age
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embryo
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• at E5.5, six of 25 sectioned embryos exhibit a smaller primary decidual zone (PDZ), as indicated by Cox2+ cells surrounding the embryos
• by E13.5, females show a higher % of resorption sites than wild-type females, indicating a possible defect in decidualization or placentation
• in vitro, primary mouse endometrial stromal cells (MESCs) show a markedly lower response to decidualization stimuli, as indicated by decidual markers
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homeostasis/metabolism
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• at 12 months of age, non-pregnant females show increased collagen deposition in the aging myometrium
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cellular
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• RNA-Seq analysis of the myometrium showed dysregulation of genes associated with cell adhesion
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• RNA-Seq analysis of the myometrium showed dysregulation of genes associated with extracellular matrix organization
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vision/eye
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• a few mice exhibit potential corneal opacity
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growth/size/body
| N |
• both male and female mice are viable with normal external appearance and normal body weights up to 6 months of age
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