reproductive system
• a dramatic reduction of DBA+ uNK cells is noted in the mesometrial pole on day 8 of pregnancy
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• although primary decidual zone (PDZ) formation appears normal during early pregnancy, development of the secondary decidual zone (SDZ) is hindered from day 7-8 of pregnancy
• terminal differentiation of stromal cells in the SDZ is impaired, with decreased decidual cell polyploidy and smaller nuclear size noted on day 8 of pregnancy
• immunofluorescence analysis showed a marked reduction in the number of polyploid decidual cells with 4 or more H3K27me3 puncta while staining for PCNA and BrdU is abnormally increased on day 8 of pregnancy
• FACS analysis of DNA content showed that 2N cells are significantly increased while >4N cells are concomitantly decreased on day 8 of pregnancy
• more stromal cells undergo proliferation in the SDZ, with a significantly increased number of PH3+ cells noted on day 8 of pregnancy
• decreased Ptx3 expression in decidual tissues on day 8 of pregnancy leads to aberrant activation of ERK1/2 in the SDZ due to unrestrained FGF2 signal emanating from undifferentiated stromal cells, which blunt Bmp2 induction and decidualization
• after oil-induced artificial decidualization, the decidual response is markedly weakened or absent on day 8 of pseudopregnancy
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• immunohistochemical staining of FOXA2 showed an increased number of glands in the lateral areas near the mesometrial pole in the uterine stroma on days 4-6 of pregnancy
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• average weight of implantation sites is significantly reduced on days 8 and 9 of pregnancy
• however, blastocyst attachment and implantation appear normal during early pregnancy
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• disrupted progression of decidualization leads to miscarriage at mid-gestation, with severe embryo absorption between days 9 and 12 of pregnancy
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• when mated with wild type fertile males, only 25% plug-positive 2-month-old females give birth to offspring vs 83% in control females, indicating severe female subfertility
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• when mated with wild type fertile males, females produce a significantly smaller litter size than control females
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embryo
• embryo development is defective at the post-implantation stage, with severe embryo absorption observed between days 9 and 12 of pregnancy
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• embryo growth is retarded in implantation sites on day 8 of pregnancy
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• eccentric expression pattern of trophoblast giant cell marker PL1 indicates shallow trophoblast invasion on day 8 of pregnancy
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• a dramatic reduction of DBA+ uNK cells is noted in the mesometrial pole on day 8 of pregnancy
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• expression of COX2 in the presumptive site of placentation is disordered on day 8 of pregnancy; placentation is obviously abnormal starting on day 9
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• although primary decidual zone (PDZ) formation appears normal during early pregnancy, development of the secondary decidual zone (SDZ) is hindered from day 7-8 of pregnancy
• terminal differentiation of stromal cells in the SDZ is impaired, with decreased decidual cell polyploidy and smaller nuclear size noted on day 8 of pregnancy
• immunofluorescence analysis showed a marked reduction in the number of polyploid decidual cells with 4 or more H3K27me3 puncta while staining for PCNA and BrdU is abnormally increased on day 8 of pregnancy
• FACS analysis of DNA content showed that 2N cells are significantly increased while >4N cells are concomitantly decreased on day 8 of pregnancy
• more stromal cells undergo proliferation in the SDZ, with a significantly increased number of PH3+ cells noted on day 8 of pregnancy
• decreased Ptx3 expression in decidual tissues on day 8 of pregnancy leads to aberrant activation of ERK1/2 in the SDZ due to unrestrained FGF2 signal emanating from undifferentiated stromal cells, which blunt Bmp2 induction and decidualization
• after oil-induced artificial decidualization, the decidual response is markedly weakened or absent on day 8 of pseudopregnancy
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cellular
• reduction of Bmp2 expression caused by aberrant activation of the ERK1/2 signaling pathway disrupts development of the SDZ due to disorganized genomic H3K4me3 modification
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endocrine/exocrine glands
• a dramatic reduction of DBA+ uNK cells is noted in the mesometrial pole on day 8 of pregnancy
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• immunohistochemical staining of FOXA2 showed an increased number of glands in the lateral areas near the mesometrial pole in the uterine stroma on days 4-6 of pregnancy
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growth/size/body
• embryo growth is retarded in implantation sites on day 8 of pregnancy
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hematopoietic system
• a dramatic reduction of DBA+ uNK cells is noted in the mesometrial pole on day 8 of pregnancy
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immune system
• a dramatic reduction of DBA+ uNK cells is noted in the mesometrial pole on day 8 of pregnancy
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