Identification of endometrial genes important for conceptus survival and development in sheep
Gray, Catherine Allison
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Recurrent early pregnancy loss in the ovine uterine gland knockout (UGKO) ewe model manifests on Day 14 of pregnancy, indicating that endometrial secretions are critical for peri-implantation conceptus development. Therefore, the following studies were conducted with fertile ewes and infertile UGKO ewes to identify candidate endometrial factors essential for normal conceptus survival, utilizing both genomics and proteomics approaches. The first study used transcriptional profiling of endometrium from Day 14 cyclic, pregnant, and bred UGKO ewes, as well as ewes treated with interferon tau (IFN??) and progesterone, to identify genes important for conceptus development. A number of novel and previously known IFN??-stimulated genes, as well as progesterone-stimulated genes were identified that are higher in fertile ewes, such as galectin-15. Interactive effects of progesterone and IFN?? regulate endometrial gene expression in a temporal and cell-type specific manner. The second study characterized the endometrial expression and hormonal regulation of galectin-15, a member of the galectin family of secreted ??-galactoside lectins. Galectin-15 was secreted into the uterine lumen by the lumenal (LE) and superficial glandular epithelium (sGE), where it may promote adhesion during implantation, as well as was phagocytosed by the trophectoderm and formed intracellular crystals. The third study determined the endometrial expression of galectin-15 throughout gestation. Galectin-15 was secreted into the uterine lumen, where it was phagocytosed by the trophectoderm/chorion, transferred through placental vasculature to the fetus, and cleared through the fetal kidney to be stored in allantoic fluid. The fourth study utilized proteomic analysis of uterine flushes and endometrial explant cultures from Day 14 cyclic, pregnant and UGKO ewes to identify differences in uterine secretions. Analyses identified several genes that were expressed by the LE and sGE and may be involved in prostaglandin production and/or pH regulation. Collectively, results of these studies suggest that transcriptional profiling and analysis of uterine secretions are effective tools to determine genes important for early pregnancy. Further, identified genes are expected to reveal novel endometrial factors and metabolic pathways for support of conceptus survival and implantation, as well as provide improvements for embryo culture methods and diagnose endometrial dysfunctions leading to infertility.