Galectins: guardians of eutherian pregnancy at the maternal-fetal interface

Abstract

Galectins are multifunctional regulators of fundamental cellular processes. They are also involved in innate and adaptive immune responses, and play a functional role in immune-endocrine crosstalk. Some galectins have attracted attention in the reproductive sciences because they are highly expressed at the maternal-fetal interface, their functional significance in eutherian pregnancies has been documented, and their dysregulated expression is observed in the 'great obstetrical syndromes'. The evolution of these galectins has been linked to the emergence of eutherian mammals. Based on published evidence, galectins expressed at the maternal-fetal interface may serve as important proteins involved in maternal-fetal interactions, and the study of these galectins may facilitate the prediction, prevention, diagnosis, and treatment of pregnancy complications.

Figure 1

Galectins promote a diverse range of responses when they contact leukocytes. Galectin-effects on innate and adaptive immune cells are depicted around the 3D model of galectin-1 dimer (1GZW) [31,55]. These effects are context-dependent and relate to the type of galectins and their intra- or extracellular localization, as well as to the type of cells and their activation and/or differentiation status [10,12,14]. Galectins as well as most types of immune cells (e.g. T cells, neutrophils, macrophages) depicted in the figure are abundant at the maternal-fetal interface. Figure adapted from [31], © Taylor & Francis.

Figure 2

Galectin expression at the maternal–fetal interface. The figure represents three interfaces where maternal and fetal cells are in direct contact from the end of the first trimester of human pregnancy. The syncytiotrophoblast of the villous placenta (depicted with gold, right side) is bathed in maternal blood, whereas invasive extravillous cytotrophoblasts in the placental bed (depicted in red, right side) and chorionic trophoblasts in the fetal membranes (depicted in red, left side) are in contact with maternal cells in the decidua (depicted in dark blue, both sides). The dysregulated expression of highly expressed galectins at the maternal–fetal interface (depicted by arrows at sites of dysregulation) is often observed in pregnancy complications. Figure adapted from [16], © National Academy of Sciences of the U.S.A.

Figure 3

Galectin evolution. (a) Maximum-likelihood phylogeny of mammalian galectin CRD amino acid sequences inferred using RaxML with a Dayhoff matrix. Prototype galectins are numbered with red (o14: sheep ‘galectin-14’), chimera-type galectin with magenta, tandem-repeat-type galectins with black (F3 domains) and blue (F4 domains), galectin-related proteins (hs, HSPC159; gr, grifin) with orange. (b) Phylogenetic relationship among closely-related genes within the galectin-13-clade cluster [15]. Genes with predominant placental expression are highlighted in red. (c) Evidence for adaptive evolution of galectins in the anthropoid cluster is represented on the molecular backbone of galectin-16. Site-specific v values are indicated by the width of the molecular backbone and by a color spectrum [15]. ω values <, =, > 1 indicate purifying selection, neutral evolution, and positive selection, respectively; v values ranged between 0.2 and 2.2. Residues with greater v are wider and nearer the red range of the color spectrum. (d) The same color-coding shows that four conserved residues (53, 65, 72, 75) in the CRDs of cluster galectins are under strong purifying (i.e. negative) selection, others on the opposite side of the CRDs (55, 57, 63, 77) show more variability [15]. Figures adapted from [15], © National Academy of Sciences of the U.S.A.