earticle

영어

For the establishment of successful pregnancy the maternal immune system must tolerate the implanting semi-allogenic conceptus, but the mechanism underlying this process is not fully understood in pigs. Among many factors, members of the tumor necrosis factor superfamily (TNFSF) have been considered as important immune regulators in cell-mediated immunity. TNFSF members bind to their responsive receptor containing cytoplasmic death domain to induce apoptosis in immune cells. Action of TNFSF members at the maternal-fetal interface during pregnancy has been studied in some species including humans, mice and cows, suggesting that apoptosis of activated maternal immune cells in the uterine endometrium is a defense mechanism against rejection of semi-allogenic fetus. However, the expression and function of TNFSF members at the maternal-conceptus interface in pigs have not fully understood. Thus, to initiate the study on the role of TNFSF members for the establishment of pregnancy, we determined the expression of CD40 ligand (CD40LG), FAS ligand (FASLG) and TNFrelated apoptosis inducing ligand (TRAIL; TNFSF10) in the uterine endometrium and conceptus tissues during pregnancy in pigs. We obtained endometrial tissues from day (D) 12 and D15 of the estrous cycle, and D12, D15, D30, D60, D90, and D114 of pregnancy, conceptus tissues on D12, D15, and chorioallantoic tissues on D30, D60, D90, and D114 of pregnancy in pigs. Real-time RT-PCR analysis showed that CD- 40LG, FASLG and TNFSF10 mRNAs were expressed in the uterine endometrium during the estrous cycle and pregnancy. Levels of CD40LG, FASLG and TNFSF10 mRNA in endometrial tissues were significantly increased on D15 of pregnancy and levels of FASLG and TNFSF10 were also high on D60 of pregnancy and decreased thereafter. Chorioallantoic tissues also expressed CD40LG, FASLG and TNFSF10 mRNA during mid- to late pregnancy. Immunohistochemical analysis showed that CD40LG and TNFSF10 proteins were mainly localized to luminal epithelial (LE) cells on D15 of pregnancy and amniotic membrane during late pregnancy, while FASLG protein was localized to LE cells during D30 to term and glandular epithelial cells during the estrous cycle and pregnancy. To understand the regulatory mechanism of endometrial CD- 40LG, FASLG and TNFSF10 expression by interferon gamma (IFNG), which is pro- duced by the implanting conceptus, we treated endometrial tissues with increasing doses of IFNG and found that IFNG increased the expression of FASLG and TNFSF10 mRNA, but not CD40LG mRNA. These results indicate that CD40LG, FASLG and TNFSF10 are expressed in a cell-type and stage-specific fashion in the uterine endometrium and chorioallantoic tissues during pregnancy, suggesting that CD40LG, FASLG and TNFSF10 may play an important role in the establishment of pregnancy by regulating the maternal immune response at the maternal-conceptus interface in pigs.