Spatiotemporal expression and regulation of adenosine receptors and the role of adenosine signaling at the maternal–conceptus interface in pigs

Adenosine (ADO), a purinergic system ligand, plays important roles in several physiological processes, including proliferation, differentiation, immunity, development, and reproduction. The activation of various intracellular signaling pathways by ADO is mediated through ADO receptors, ADORA1, ADORA2A, ADORA2B, and ADORA3. Although the importance of ADO during pregnancy has been studied in some species, the expression of ADO receptors and the roles of ADO at the maternal-conceptus interface have not been studied in pigs. Therefore, we investigated the expression and regulation of ADO receptors and the function of ADO at the maternal-conceptus interface in pigs. The expression of ADO receptors in the endometrium changed dynamically during pregnancy, and the levels of ADORA1, ADORA2A, and ADORA3 expression were greater during early pregnancy than during the estrous cycle. During pregnancy, both conceptus and chorioallantoic tissues expressed ADO receptors. Estradiol-17β, interleukin-1β, and/or interferon-γ increased the endometrial expression of ADORA1 and ADORA2A. Total recoverable amounts of ADO in the uterine lumen were greater on Day 15 of pregnancy than on Day 15 of the estrous cycle. Increasing doses of ADO increased the expression of prostaglandin (PG) synthetic enzymes, PGF2α secretion, and the activation of mitogen-activated protein kinases in endometrial epithelial (pUE) cells, and migration of conceptus trophectoderm cells in vitro. These data suggest that conceptus-derived factors affect the endometrial expression of ADO receptors and ADO production. Therefore, ADO plays important roles in the regulation of pUE cells and conceptus trophectoderm cell functions at the maternal-conceptus interface to establish and maintain pregnancy in pigs.