Galectin-1 is an anti-inflammatory lectin with pleiotropic regulatory functions at the crossroads of innate and adaptive immunity. It is expressed in immune privileged sites and is implicated in establishing maternal-fetal immune tolerance, which is essential for successful pregnancy in eutherian mammals. Here, we show conserved placental localization of galectin-1 in primates and its predominant expression in maternal decidua. Phylogenetic footprinting and shadowing unveil conserved cis motifs, including an estrogen responsive element in the 5 promoter of LGALS1, that were gained during the emergence of placental mammals and could account for sex steroid regulation of LGALS1 expression, thus providing additional evidence for the role of galectin-1 in immuneendocrine cross-talk. Maximum parsimony and maximum likelihood analyses of 27 publicly available vertebrate and seven newly sequenced primate LGALS1 coding sequences reveal that intense purifying selection has been acting on residues in the carbohydrate recognition domain and dimerization interface that are involved in immune functions. Parsimony-and codon model-based phylogenetic analysis of coding sequences show that amino acid replacements occurred in early mammalian evolution on key residues, including gain of cysteines, which regulate immune functions by redox status-mediated conformational changes that disable sugar binding and dimerization, and that the acquired immunoregulatory functions of galectin-1 then became highly conserved in eutherian lineages, suggesting the emergence of hormonal and redox regulation of galectin-1 in placental mammals may be implicated in maternal-fetal immune tolerance.decidua ͉ estrogen ͉ glycocode ͉ immune-endocrine cross-talk ͉ pregnancy T he success of mammalian pregnancy, in which the developing fetus and mother exchange nutrients, gases, and other molecules via the chorioallantoic placenta, requires maternal immune tolerance to fetal allo-antigens (1-4). This tolerance presumably prevents the occurrence of exaggerated inflammation at the implantation site and reduces the danger of destructive immune attacks on the fetus, a danger that the first mammals with an invasive placenta would have faced (5, 6). It seems likely that mechanisms for immune tolerance to invasive placentation were already functioning in the early placental mammals and that immunoregulatory molecules, which had existed before the mammalian placenta evolved, were incorporated in this tolerance and have undergone evolutionary modifications coincident with the emergence of the mammalian placenta. Here, we present evidence that such modifications occurred in a key immunoregulatory molecule, galectin-1.Molecules that have been implicated in conferring maternalfetal immune tolerance include galectin-1, B7 proteins, Crry, Fas ligand, HLA-G, indoleamine 2,3-dioxygenase, and killer cell immunoglobulin-like receptors (2-4, 7-11). These proteins are involved in pathways regulating adaptive or innate immune responses at the maternal-fetal interface, and their di...

OBJECTIVE The purpose of this study was to compare the transcriptome between the site of membrane rupture and the chorioamniotic membranes away from the site of rupture. STUDY DESIGN The transcriptome of amnion and chorion (n =20 each) from and distal to the site of rupture from women with spontaneous labor and vaginal delivery at term after spontaneous rupture of membranes was profiled with Illumina HumanHT-12 microarrays. Selected genes were validated with the use of quantitative reverse transcription–polymerase chain reaction. RESULTS Six hundred seventy-seven genes were differentially expressed in the chorion between the rupture and nonrupture sites (false discovery rate <0.1; fold change >1.5). Quantitative reverse transcription–polymerase chain reaction confirmed the differential expression in 10 of 14 genes. Enriched biological processes included anatomic structure development, cell adhesion and signal transduction. Extracellular matrix–receptor interaction was the most impacted signaling pathway. CONCLUSION The transcriptome of fetal membranes after spontaneous rupture of membranes in term labor is characterized by region-and tissue-specific differential expression of genes that are involved in signature pathways, which include extracellular matrix–receptor interactions.

Objective Galectin-1 is a major anti-inflammatory protein expressed by the placenta and immune cells that can bias the character of inflammatory responses toward the Th2 type. Galectin-1 is expressed in immune privileged sites, it can facilitate immune tolerance and tumor immune escape, and it has been successfully used for the suppression of experimental autoimmune diseases as well as graft versus host disease in murine models. We propose that an abnormal immune response in some pregnancy complications may be associated with changes in placental expression of galectin-1. To test this hypothesis, we studied placental galectin-1 mRNA and protein expression and localization in women with preeclampsia (PE) and in those who delivered a small-for-gestational age (SGA) neonate. Study design This cross-sectional study included pregnant women matched for gestational age at delivery in the following groups: 1) severe PE (n=10); 2) severe PE complicated with SGA (n=10); 3) SGA without PE (n=10); and 4) controls (n=10). Galectin-1 mRNA and protein were localized in placentas by in situ hybridization and immunofluorescence microscopy. Galectin-1 mRNA expression was determined by quantitative real-time RT-PCR, and galectin-1 protein content by Western blot. Non-parametric statistics were used for analysis. Results 1) In normal term placentas, galectin-1 mRNA or immunofluorescence signals were detected in the trophoblasts, villous stromal cells, Hofbauer cells, endothelial cells of the villous blood vessels,,and the villous stroma. 2) Placental galectin-1 mRNA expression was significantly higher in severe PE (with or without SGA) than in controls (1.47 fold, p=0.004; 1.44 fold, p=0.003; respectively] and in SGA (1.68 fold, p=0.001; 1.64 fold, p=0.001; respectively]. 3) Trophoblasts in placentas of patients with severe PE had the most intense galectin-1 immunostaining. Conclusion 1) We report for the first time the placental expression and localization of galectin-1 mRNA and demonstrate that the protein is abundantly present in third trimester human placentas. 2) Placental galectin-1 expression is higher in severe PE than in normal pregnancy regardless of the presence of SGA. 3) However, it is not altered in SGA without PE. We propose that the increased placental expression of galectin-1 in patients with severe PE may represent a fetal response to an exaggerated systemic maternal inflammation; thus, galectin-1 may be implicated in maternal-fetal immune tolerance in humans.