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Regulation of uterine genes during the peri-implantation period, and its relationship to gene expression changes in the maternal brain in gestating mice (FAIRE-seq)

ABSTRACT: In this study, we conducted an integrated analysis of gene expression and chromatin structure of mouse uterus to understand the regulation of uterine expressed genes on gestation day (GD) 4 during the peri-implantation period.

ORGANISM(S): Mus musculus

PROVIDER: GSE139311 | GEO | 2019/10/24

REPOSITORIES: GEO

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Regulation of uterine genes during the peri-implantation period, and its relationship to gene expression changes in the maternal brain in gestating mice (RNA-seq)

Project description:In this study, we conducted an integrated analysis of gene expression and chromatin structure of mouse uterus to understand the regulation of uterine expressed genes on gestation day (GD) 4 during the peri-implantation period.

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Metabolic Changes of Maternal Uterine Fluid, Uterus, and Plasma during the Peri-implantation Period of Early Pregnancy in 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.

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Mouse uterine gene expressions during peri-implantation period

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Project description:Conceptus implantation to the uterine endometrium is required for pregnancy establishment, during which non-invasive trophoblasts attach and adhere to the uterine endometrium or invasive trophoblasts invade into the uterine stroma, followed by placental formation in most mammalian species. During peri-implantation period, conceptuses must communicate with the uterine endometrium if they are to survive and proceed to attachment to the uterine epithelium. Despite numerous studies performed on the bovine species, molecular mechanisms associated with their attachment processes, particularly the initial attachment to the endometrial epithelium, have not been well characterized.

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Transcriptomic analysis of the porcine anterior pituitary gland during the peri-implantation period

Project description:In pigs, the peri-implantation period is recognized as determinant of successful reproduction, and it is controlled by neuroendocrinal interactions among signals originating from the female hypothalamic-pituitary-ovarian axis, uterus, and developing embryo. The transcriptomic activity of the pituitary gland may influence reproductive processes occurring in pigs during the peri-implantation period. The aim of this study was to determine alternations in gene expression in the porcine pituitary gland during the peri-implantation period (days 15-16 of pregnancy) in comparison with that during the respective days of the estrous cycle using a microarray approach.

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Uterine glands impact uterine receptivity, luminal fluid homeostasis and blastocyst implantation

Project description:Uterine glands are essential for pregnancy in mice and likely humans, because they secrete or transport bioactive substances that regulate uterine receptivity for blastocyst implantation. In mice, the uterus becomes receptive to blastocyst implantation on day 4, but is refractory by day 5. Here, blastocysts could be recovered from progesterone-induced uterine gland (PUGKO) but not wildtype (WT) mice on day 5 post-mating. Anti-adhesive Muc1 protein and microvilli were present on the luminal epithelium of PUGKO but not WT uteri. A number of known uterine receptivity genes and gland-specific genes were altered in the PUGKO uterus. Next, the uterus and uterine luminal fluid (ULF) were obtained from WT and PUGKO mice on day 3, 4 and 5. Transcriptome analysis revealed that 580 genes were decreased in the PUGKO uterus, however ULF secrotome analysis revealed that many proteins and several amino acids were increased in the PUGKO ULF. Of note, many proteins encoded by many gland-specific genes were not identified in the ULF of WT mice. These results support the ideas that uterine glands secrete factors that regulate ULF homeostasis and interact with other cell types in the uterus to influence uterine receptivity and blastocyst implantation for the establishment of pregnancy.

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Regulation of uterine genes during the peri-implantation period, and its relationship to gene expression changes in the maternal brain in gestating mice (FAIRE-seq)

Project description:Regulation of uterine genes during the peri-implantation period, and its relationship to gene expression changes in the maternal brain in gestating mice (FAIRE-seq)

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Regulation of uterine genes during the peri-implantation period, and its relationship to the maternal brain in gestating mice.

Project description:We conducted an integrated analysis of gene expression and chromatin structure of mouse uterus to understand the regulation of uterine-expressed genes on gestation day 4 (GD4) during the peri-implantation period. The genes expressed in the uterus showed a significant association (p < .0001) with the presence of the nucleosome-free region (open chromatin) in the 5'-untranslated region of the genes. The majority of these upstream open chromatins harbored a common class of regulatory elements known as upstream open reading frames. We also compared the gene expression profiles between the uterus and brain which showed that specific gene pairs were expressed in a correlated manner, either positively or negatively. In addition, specific ligand/receptor genes showed coordinated patterns of expression between the uterus and brain on GD4, and the level of expression of these ligand/receptors altered significantly in the brain during late pregnancy (GD15) compared with the peri-implantation period (GD4). Collectively, these results suggest that regulation of the uterine genes during the peri-implantation period is likely to have a functional link with the maternal brain in pregnant mice.

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Cytochrome P450 26A1 Modulates the Polarization of Uterine Macrophages During the Peri-Implantation Period.

Project description:Uterine M1/M2 macrophages activation states undergo dynamic changes throughout pregnancy, and inappropriate macrophages polarization can cause adverse pregnancy outcomes, especially during the peri-implantation period. Our previous studies have confirmed that Cytochrome P450 26A1 (CYP26A1) can affect embryo implantation by regulating uterine NK cells and DCs. The aim of this study was to investigate whether CYP26A1 regulates the polarization of uterine macrophages in early pregnancy. Here, we observed that Cyp26a1 was significantly upregulated in M1 as compared with M2 of uterine macrophages, Raw264.7 and iBMDM. Knockdown of CYP26A1 in mice uterine significantly decreased the number of embryo implantation sites and the proportion of CD45+F4/80+CD206 - M1-like uterine macrophages. Primary uterine macrophages treated with anti-CYP26A1 antibody expressed significantly lower levels of M1 markers Nos2, Il1b, Il6 and Tnf-a. In CYP26A1 knockout Raw264.7 cells, the protein levels of M1 markers TNF-α, IL-6 and CD86 were significantly decreased as compared with the wild type cells. Moreover, CYP26A1 deficiency decreased the ability to produce nitric oxide and increased the phagocytosis capacity of Raw264.7 cells under M1 stimulation state. The re-introduction of CYP26A1 partially reversed the polarization levels of M1 in CYP26A1 knockout Raw264.7 cells. CYP26A1 may regulate the polarization of uterine macrophages to M1 through Stap1 and Slc7a2. In summary, these results indicate that CYP26A1 plays a significant role in macrophage polarization, and knockdown of CYP26A1 can cause insufficient M1 polarization during the peri-implantation period, which has adverse effects on blastocyst implantation.

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