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(EX2) HORMONAL, CELLULAR, AND MOLECULAR ASPECTS OF UTERINE DEVELOPMENT AND FUNCTION: INSIGHTS FROM THE EWE. Spencer, Thomas1, 1 Texas A&M University, College Station, TX ABSTRACT- Uterine adenogenesis is the process whereby endometrial glands differentiate and develop and is primarily a postnatal event in all mammals. In domestic animals and humans, adenogenesis involves initial differentiation and budding of glandular epithelium followed by invagination and extensive tubular coiling and branching morphogenesis through the endometrial stroma to the myometrium. Ovine endometrial adenogenesis is regulated by hormones (prolactin) as well as intrinsic epithelial-stromal growth factor systems and transcription factors. Transient exposure of the neonatal ewe to endocrine disruptors (progestins or estrogens) during critical periods specifically alters growth factor networks that perturb normal development of the uterus. Chronic exposure of the neonatal ewe to a progestin from birth to postnatal Day 56 results in a uterine gland knock out (UGKO) phenotype in the adult. UGKO ewes exhibit a peri-implantation defect in conceptus (embryo/fetus and associated extraembryonic membranes) survival, indicating the functional importance of uterine glands and their secretions. Genomic and proteomic analysis of uterine endometrium from UGKO ewes has identified many candidate genes that regulate conceptus development and implantation, including endogenous Jaagsiekte sheep retroviruses (enJSRVs) and galectin-15. Galectin-15 is a novel secreted animal lectin that forms crystal inclusions in the trophectoderm. During early pregnancy, the ovine conceptus releases the pregnancy recognition hormone interferon tau which inhibits development of the endometrial luteolytic mechanism and stimulates expression of genes such as galectin-15 and Wnt7a. In sheep, the sequential actions of ovarian steroid hormones (estrogen and progesterone), interferon tau, placental lactogen and placental growth hormone constitute a servomechanism that directly regulates endometrial gland morphogenesis and terminal differentiated function to provide increasing histotrophic nutrition for conceptus growth and development. Knowledge gained from this research will be used to prevent or treat infertility, fetal growth retardation, and disease in domestic animals and humans. Supported by NIH and USDA grants. KEY WORDS: uterus, function, ovine, development |
