Project description:We used the microarray analysis to determine the differential gene expression profiles in mouse uterine luminal epithelium between preimplantation gestation day 3.5 and postimplantation gestation day 4.5, and investigeate the molecular mechanism of the establishment of uterine receptivity and embryo implantation. Uterine luminal epithelium (LE) is critical for the establishment of uterine receptivity during embryo implantation. Many genes are known to have differential expression in the periimplantation LE but the global profiling of the altered genes in the periimplantation LE is unknown. To fill in this knowledge gap, microarray analysis was performed in gestation day 3.5 (D3.5, preimplantation) and D4.5 (postimplantation) mouse LE from natural pregnancy. There were 382 significantly upregulated and 245 significantly downregulated genes (>2 fold, P<0.05) in the D4.5 LE. There are 6 samples. 3 for gestation day 3.5 uterine luminal epithelium, the other 3 for gestation day 4.5 uterine luminal epithelium
Project description:We used the microarray analysis to determine the differential gene expression profiles in mouse uterine luminal epithelium between preimplantation gestation day 3.5 and postimplantation gestation day 4.5, and investigeate the molecular mechanism of the establishment of uterine receptivity and embryo implantation. Uterine luminal epithelium (LE) is critical for the establishment of uterine receptivity during embryo implantation. Many genes are known to have differential expression in the periimplantation LE but the global profiling of the altered genes in the periimplantation LE is unknown. To fill in this knowledge gap, microarray analysis was performed in gestation day 3.5 (D3.5, preimplantation) and D4.5 (postimplantation) mouse LE from natural pregnancy. There were 382 significantly upregulated and 245 significantly downregulated genes (>2 fold, P<0.05) in the D4.5 LE.
Project description:Conditional ablation of Indian hedgehog (Ihh) in the murine uterus results in mice that are sterile due to defects in embryo implantation. We performed microarray analysis on these mice at the time point at which the Ihh target genes are induced by the administration of exogenous hormone to mimic day 3.5 of pregnancy. This analysis identified 863 genes altered by the conditional ablation of Ihh. Of these, genes that regulated the cell cycle were overrepresented. In addition, genes involved in epidermal growth factor (EGF) and estrogen (E2) signaling were found to be deregulated upon Ihh ablation. Furthermore, upon conditional ablation of Ihh, 15 month old mice exhibited hallmarks of estrogenized uteri such as cystically dilated glands and hyalinized stroma. Thus, Ihh regulates embryo implantation by impacting the cell cycle, EGF signaling, and E2 signaling. Keywords: two group comparison We conditionally ablated Indian hedgehog in the mouse uterus using the PRcre mouse model (PRcre/+Ihhf/f; Ihhd/d). High density DNA microarray analysis was performed on Day -1 of the artificial decidual response on Ihhf/f and Ihhd/d uteri.
Project description:Comparison of the gene expression profiles of pre-implantation embryos at day 3.5 post coitum from normal pregnant mice (control); embryos from mice treated with ICI (specific estrogen receptor inhibitor); and embryos in the oviduct that were blocked from entering the uterus by ligation. Results provide insight into the function of estrogen regulated genes and uterine factors involved in the early implantation process. RNA were extracted from 3 groups of 100-120 embryos (a) embryos at d3.5 from uterus of normal pregnant mice; (b) embryos at d3.5 from uterus of ICI treated mice; and (c) embryos at d3.5 from the ligated oviduct.
Project description:Conditional ablation of Indian hedgehog (Ihh) in the murine uterus results in mice that are sterile due to defects in embryo implantation. We performed microarray analysis on these mice at the time point at which the Ihh target genes are induced by the administration of exogenous hormone to mimic day 3.5 of pregnancy. This analysis identified 863 genes altered by the conditional ablation of Ihh. Of these, genes that regulated the cell cycle were overrepresented. In addition, genes involved in epidermal growth factor (EGF) and estrogen (E2) signaling were found to be deregulated upon Ihh ablation. Furthermore, upon conditional ablation of Ihh, 15 month old mice exhibited hallmarks of estrogenized uteri such as cystically dilated glands and hyalinized stroma. Thus, Ihh regulates embryo implantation by impacting the cell cycle, EGF signaling, and E2 signaling. Keywords: two group comparison
Project description:To identify genes differentially expressed in the glandless uterus, whole uteri were collected from control (uterine glands present) and PUGKO (no uterine glands) mice at day of pseudopregnancy (DOPP) 3.5 (day DOPP 0.5= vaginal plug). Microarray analysis identified differentially expressed genes in the glandless uteri of PUGKO mice as compared to control mice.
Project description:Embryo implantation is a complex process which involves biochemical and physiological interactions between an implantation-competent blastocyst and a receptive uterus. However, the exact biochemical changes of uterine fluid, uterus, and plasma during peri-implantation remain unclear. This study aims to characterize the biochemical and metabolic changes that occur during the peri-implantation period of early pregnancy, using mice as an animal model. Gas chromatography-mass spectrometry was used to analyze the metabolite profiles of the uterus, uterine fluid, and maternal plasma at pre-implantation and implantation. The multivariate analyses, ANOVA and Tukey's HSD test, were applied to detect significant changes in metabolites and metabolic pathways. The metabolic networks were reconstructed in silico based on the identified metabolites and KEGG metabolic framework. Between pre-implantation day 1 and day 4, dramatic metabolic changes were observed in the uterine fluid that could be important for blastocyst development and protection against the harsh uterine environment. Palmitoleic acid, fumaric acid, and glutaric acid changed levels at day 4 in the uterus, suggesting that they may be associated with endometrial receptivity. Both the uterus and maternal plasma showed profound changes in cellular metabolism at the early implantation period, including upregulation of branched-chain amino acids and intermediates of one-carbon metabolism, an upregulation of glyoxylate and dicarboxylate metabolism, and downregulation of aerobic respiration; all of which could be involved in the regulation of the maternal-fetal interface, alternative nutrient utilization, and energy preservation for implantation as well as later placentation and fetal development to ensure successful embryo implantation.
Project description:We generated mice with single or double conditional inactivation of SMAD1 and SMAD5 using progesterone receptor (PR) cre (Smad1flox/flox;Smad5flox/flox;Pgr-cre+/-, or “Smad1/5 cKO”). Female mice with single SMAD1 or SMAD5 deletion were subfertile, whereas Smad1/5 cKO were infertile and had no visible implantation sites at 4.5 days post-coitum (dpc), indicating functional redundancy of SMAD1 and SMAD5. Histological and molecular analyses of the Smad1/5 cKO uteri during pregnancy determined that the infertility was the result of impaired uterine receptivity. During the window of implantation, uteri of Smad1/5 cKO mice responded abnormally to estradiol (E2) and to progesterone (P4), retained luminal PR expression, and displayed cytoplasmic FOXO1 mis-localization. Furthermore, uteri of Smad1/5 cKO mice did not respond to an artificial decidual stimulus and the stroma failed to differentiate. To determine the cell surface receptor complex that controls BMP signaling during implantation, we generated mice with conditional deletion of Acvr2a and Acvr2b using Pgr-cre+/-. We determined that Acvr2b cKO females were subfertile, while Acvr2a cKOs were infertile and displayed a range of ovarian and uterine abnormalities, including endometrial and implantation defects that phenocopied those of Smad1/5 cKO mice. Transcriptomic profiling of the Smad1/5 cKO and Acvr2a cKO uterus showed that genes involved in epithelial cell remodeling and microvilli/ciliated cell function were overrepresented in both genotypes. These results demonstrate that BMP signals mediated via ACVR2A and SMAD1/5 control endometrial receptivity and embryo implantation by remodeling the apicobasal polarity of the epithelium during the window of implantation.