Regulation of Nod-like receptor expression in the liver of ewes during early pregnancy

pregnancy-ABSTRACT. Multiple factors are involved in the regulation of maternal-foetal tolerance, and nucleotide-binding and oligomerisation domain (NOD)-like receptors (NLRs) were shown to play roles in innate immune signalling pathways. The objective of this study was to investigate the effects of early pregnancy on the expression of NLRs in the liver of ewes. Livers from ewes were collected on day 16 of the oestrous cycle, and days 13, 16 and 25 of gestation (n = 6 for each group). Real-time quantitative PCR, Western blot and immunohistochemical analysis were used to analyse mRNA and protein expression of NLRs, including NOD1, NOD2, major histocompatibility complex class II transactivator (CIITA), neuronal apoptosis inhibitor protein (NAIP), NLR family, pyrin domain-containing 1 (NLRP1), NLRP3 and NACHT, LRR and PYD domains-containing protein 7 (NLRP7). The data showed that NOD1, CIITA, NLRP1, NLRP3 and NLRP7 were upregulated in maternal liver on days 13 to 25 of pregnancy, and NOD2 expression was upregulated on days 13 and 16 of pregnancy, but downregulated on day 25 of pregnancy. In addition, NOD2 and NLRP7 proteins were located in the endothelial cells of the proper hepatic arteries and portal veins, and in hepatocytes. NAIP expression was the highest at day 16 of pregnancy. In conclusion, this study reported for the first time that early pregnancy modulated the expression of NLRs, suggesting that NLRs were involved in the regulation of maternal hepatic immune functions during early pregnancy in sheep.