(208) Expression and Regulation of Nucleoside and Nucleobase Transporters and Function of Extracellular Adenine at the Maternal-Conceptus Interface in Pigs

Yugyeong Cheon, Eunhyeok Choi, Seonghyun Kim, and Hakhyun Ka

Division of Biological Science and Technology, Yonsei University, Wonju, 26493, Republic of Korea.

Abstract Text:

The purinergic system is involved in a variety of physiological processes, including development, metabolism, immunity, neuronal function, reproduction, and tumorigenesis. Recently, we have reported that purinergic system molecules, including adenosine triphosphate (ATP) and adenosine (ADO), converting enzymes, ATP transporters, and ATP and ADO receptors, are expressed at the maternal-conceptus interface and extracellular ATP and ADO play an important role in the establishment of pregnancy by regulating endometrial epithelial and conceptus trophectoderm cell functions. Adenine (ADE), a nitrogenous base, is an essential component of ATP, ADO, and cofactors such as nicotinamide-adenine dinucleotide and flavin adenine dinucleotide. However, the expression of nucleoside and nucleobase transporters [solute carrier protein 28A (SLC28A) and SLC29A families] and the roles of extracellular ADE at the maternal-conceptus interface in pigs has not been studied. Thus, this study determined the expression and regulation of SLC28A (SLC28A1, SLC28A2, and SLC28A3) and SLC29A families (SLC29A1, SLC29A2, SLC29A3, and SLC29A4) and roles of extracellular ADE at the maternal-conceptus interface in pigs. We found that members of the SLC28A and SLC29A families were expressed in the endometrium during the estrous cycle and pregnancy in a stage-specific manner, and the expression of SLC29A2 was greater on Day 12 of pregnancy than the estrous cycle. Conceptus tissues during early pregnancy and chorioallantoic tissues during mid- to term pregnancy also expressed the SLC28A and SLC29A families. SLC29A1 and SLC29A3 mRNAs and SLC29A2 protein were localized to endometrial and chorionic epithelial cells during pregnancy. Interleukin-1β increased SLC29A2 expression in endometrial tissues. To understand the function of ADE, we treated porcine endometrial epithelial (pUE) and conceptus trophectoderm (pTr) cells with increasing doses of ADE in vitro and measured cell proliferation and migration and the expression of genes related to prostaglandins (PGs) and pro- and anti-inflammatory cytokines. We found that ADE did not affect cell proliferation of pUE and pTr cells, but decreased migration of pUE cells and increased migration of pTr cells. Furthermore, ADE increased the expression of genes related to PGs and cytokines in pUE and pTr cells. These results in pigs showed that nucleoside and nucleobase transporters are expressed at the maternal-conceptus interface and ADE regulates migration of pUE and pTr cells and the expression of molecules related to PGs and cytokines in pUE and pTr cells. These suggest that nucleoside and nucleobase transporters and ADE may play an important role in the establishment of pregnancy by regulating cell migration and cytokine production in endometrial epithelial and trophectoderm cells at the maternal-conceptus interface during pregnancy in pigs. [This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science & ICT; #RS-2025-00518549), Republic of Korea]