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- W2525779849 abstract "Implantation is regulated by a timely interplay of the steroid hormones, estrogen (E) and progesterone (P). A transient surge of E immediately preceding implantation is believed to trigger the expression of a unique set of genes that critically control embryo attachment and subsequent decidualization. To identify these E-induced genes, we utilized a delayed implantation mouse model in which embryo attachment to Pprimed pregnant uterus is dependent upon the administration of E. We performed gene expression profiling using oligonucleotide microarrays to identify several genes that are up-regulated in the delayed uteri in response to E. One of these genes encoded the cyclin-dependent kinase 1 (Cdk1), which is known to regulate the G2-M phase of the cell cycle. Analysis by quantitative PCR of total RNA obtained from uteri of delayed mice treated with or without E indicated a significant increase in the level of Cdk1 mRNA within 1 h of E administration, confirming the E regulation of this gene. Immunohistochemical localization of Cdk1 protein during delayed implantation revealed its enhanced expression in the subepithelial stromal cells in response to E. Interestingly, the stromal cells in the immediate vicinity of the implanting embryo were devoid of Cdk1 expression. We further explored the expression of Cdk1 in the stromal compartment during normal pregnancy. While a robust expression of Cdk1 was localized in the stromal cells of the secondary decidual zone (SDZ) on days 5 to 7 of gestation, its expression was undetectable in the stromal cells of the primary decidual zone (PDZ). This pattern of Cdk1 expression precisely overlapped with that of ERα, consistent with our hypothesis that Cdk1 is a downstream target of regulation by E in the stromal cells at the time of decidualization. Localization of PCNA, a marker of cell proliferation, showed that the stromal cells of both PDZ and SDZ entered the cell cycle and proceeded to the S phase. However, immunohistochemical analysis of the mitosis marker phospho-histone 3 indicated the presence of mitotic activity only in the stromal cells of the SDZ but not in the PDZ. The expression of cyclin B2, the activating cyclin partner of Cdk1, was observed in both PDZ and SDZ. Collectively, these results provided novel insights into the mechanisms by which E exerts differential proliferating effects in the PDZ and SDZ during decidualization. While it promotes cell cycle entry and mitosis of the stromal cells in the SDZ via induction of Cdk1, it fails to stimulate the proliferation of the stromal cells of PDZ, which remain blocked at the G2-M phase, presumably due to a lack of ERα and Cdk1 expression. It is conceivable that these cell-type specific proliferative effects of E contribute to differential architecture, function and cell-fate of the PDZ and SDZ during early gestation (Supported by NIH grants). (poster)" @default.
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- W2525779849 date "2007-07-01" @default.
- W2525779849 modified "2023-10-16" @default.
- W2525779849 title "ESTROGEN DIFFERENTIALLY REGULATES THE EXPRESSION OF CYCLIN-DEPENDENT KINASE 1 (Cdk1) IN PRIMARY AND SECONDARY DECIDUAL COMPARTMENTS DURING IMPLANTATION" @default.
- W2525779849 doi "https://doi.org/10.1093/biolreprod/77.s1.101" @default.
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