Expression and Regulation of Nucleoside/Nucleobase Transporters and the Role of Adenine at the Maternal-Conceptus Interface in Pigs.

Purine nucleosides and nucleobases such as adenine (ADE) and adenosine (ADO) move through cellular transporters and play essential roles in various physiological processes, including proliferation, differentiation, immunity, and pregnancy. The cellular uptake of ADE, ADO, and other purine metabolites via these transporters regulates intracellular nucleotide pools and supports purine salvage pathways, thereby maintaining metabolic homeostasis and cellular function. Although the importance of nucleoside/nucleobase transporters during pregnancy has been studied in some species, their expression and the role of ADE at the maternal-conceptus interface have not been evaluated in pigs. Therefore, we investigated the expression and regulation of nucleoside/nucleobase transporters SLC28As, SLC29As, and SLC43A2 and the function of ADE at the maternal-conceptus interface in pigs. The expression of nucleoside/nucleobase transporters in the endometrium varied dynamically during pregnancy, and the localization of these transporters was cell type-specific. During pregnancy, both conceptus and chorioallantoic tissues expressed nucleoside/nucleobase transporters. Interleukin-1β increased the expression of SLC29A2 and a calcium ionophore decreased the expression of SLC28A2 and SLC29A3 in endometrial explants. Increasing doses of ADE increased the expression of prostaglandin (PG) synthetic enzymes and transporters and cytokines in endometrial epithelial cells and the expression of PG synthetic enzymes and transporters as well as implantation-related genes, and migration of conceptus trophectoderm cells in vitro. These data suggest that the expression of nucleoside/nucleobase transporters is dynamically regulated at the maternal-conceptus interface and ADE may play important roles in regulation of endometrial epithelial and conceptus trophectoderm cell function during the establishment and maintenance of pregnancy in pigs.