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• W2141252904 abstract "Tryptophan 2,3-dioxygenase (TDO) is expressed in endometrium and catabolizes tryptophan, a precursor in the biosynthesis of serotonin. Tryptophan metabolism is an important mechanism for regulation of serotonin levels. Preimplantation mouse embryos are known to express serotonin receptors, specifically the 5-HT1D and 5-HT7 serotonin receptor subtypes. Here we demonstrate that Hoxa10 regulates endometrial TDO expression and improves embryo viability through increased serotonin production. Transfection of pcDNA-Hoxa10 to the murine uterus increased total TDO expression. In vitro, epithelial cell TDO expression was decreased after transfection with Hoxa10. Decreased glandular TDO in response to HOXA10 may augment serotonin production by increasing tryptophan availability. Conversely, stromal TDO expression increased with constitutive Hoxa10 expression. In mice, epithelial serotonin was increased in response to constitutive expression of Hoxa10. Embryo quality was impaired after treatment with Hoxa10 antisense. Blockade of serotonin receptors 1D and 7 also resulted in impaired embryo development, indicating an essential role for Hoxa10 induction of TDO and subsequent serotonin production in embryo development. Transfection of pcDNA-TDO also decreased the number of T cells in the endometrial stroma. We have shown a novel mechanism by which HOXA10 regulates endometrial TDO expression. In the endometrial stroma, HOXA10 increases TDO mRNA, which may increase tryptophan catabolism, allowing for immune tolerance at the time of embryo implantation. In endometrial glands, HOXA10 decreases TDO mRNA leading to increased serotonin that in turn acts to promote normal embryo development." @default.
• W2141252904 created "2016-06-24" @default.
• W2141252904 creator A5031241757 @default.
• W2141252904 creator A5066860578 @default.
• W2141252904 creator A5073212927 @default.
• W2141252904 date "2011-01-01" @default.
• W2141252904 modified "2023-10-01" @default.
• W2141252904 title "Regulation of tryptophan 2,3-dioxygenase by HOXA10 enhances embryo viability through serotonin signaling" @default.
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• W2141252904 doi "https://doi.org/10.1152/ajpendo.00439.2010" @default.
• W2141252904 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3023205" @default.
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• W2141252904 hasPublicationYear "2011" @default.
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