reproductive system
• females failed to undergo a decidual reaction in response to estradiol (E2) plus progesterone (P4) treatment, with no increase in uterine size and weight or change in stromal cell shape and alkaline phosphatase staining in the stimulated horn on day 2 and day 5 after decidual stimulation
• mRNA levels of several genes critical for proliferation and differentiation of endometrial stromal cells were significantly reduced in the stimulated horn 5 days after stimulation
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• in response to E2 treatment, uteri of ovariectomized (OVX) mice showed alterations in endometrial epithelial morphology resulting in a transition from a simple epithelium to a stratified squamous epithelium with increased TRP63 expression
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• no embryo implantation sites were detected at day 5.5 of pregnancy
• however, serum P4 levels were normal at day 5.5 of pregnancy
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• uteri of OVX mice showed significantly reduced progesterone receptor (PGR) protein levels in the luminal and glandular epithelia at both baseline and in response to P4 stimulation
• uteri of OVX mice showed a complete loss of P4-dependent induction of PGR-regulated genes Areg and Cyp26a1 as well as decreased Ihh mRNA expression at both baseline and in response to P4, indicating attenuated P4 signaling
• P4 treatment failed to regulate 97% of P4 response genes in OVX uteri; many of the remaining P4 response genes showed reduced magnitude on change of gene expression in response to P4
• day 3.5 pseudopregnancy uteri showed uninhibited estrogen signaling with higher E2 signaling activities in the absence of elevated ESR1 levels and abnormally high uterine epithelial proliferation, unlike control uteri where epithelial proliferation was high at day 2.5 but reduced at day 3.5
• uteri of OVX mice showed ectopic expression of TRP63 in a layer of cells, morphologically similar to basal cells, underneath the columnar luminal epithelia and a cancer-related molecular profile
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• all 8-week-old female mice mated with wild-type males failed to produce offspring over a 6-month breeding period
• however, females subjected to a superovulatory regimen ovulated a similar number of eggs as control females
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embryo
• females failed to undergo a decidual reaction in response to estradiol (E2) plus progesterone (P4) treatment, with no increase in uterine size and weight or change in stromal cell shape and alkaline phosphatase staining in the stimulated horn on day 2 and day 5 after decidual stimulation
• mRNA levels of several genes critical for proliferation and differentiation of endometrial stromal cells were significantly reduced in the stimulated horn 5 days after stimulation
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