Galectins: Important Regulators in Normal and Pathologic Pregnancies

Abstract

Galectins (Gal) are characterized by their affinity for galactoside structures on glycoconjugates. This relationship is mediated by carbohydrate recognition domains, which are multifunctional regulators of basic cellular biological processes with high structural similarity among family members. They participate in both innate and adaptive immune responses, as well as in reproductive immunology. Recently, the discovery that galectins are highly expressed at the maternal-fetal interface has garnerd the interest of experts in human reproduction. Galectins are involved in a variety of functions such as maternal-fetal immune tolerance, angiogenesis, trophoblast invasion and placental development and are considered to be important mediators of successful embryo implantation and during pregnancy. Dysregulation of these galectins is associated with abnormal and pathological pregnancies (e.g., preeclampsia, gestational diabetes mellitus, fetal growth restriction, preterm birth). Our work reviews the regulatory mechanisms of galectins in normal and pathological pregnancies and has implications for clinicians in the prevention, diagnosis and treatment of pregnancy-related diseases.

Keywords: fetal growth restriction; galectin; gestational diabetes mellitus; maternal–fetal interface; pathologic pregnancy; preeclampsia; preterm birth.

Figure 1

The classification and structure of galectins. The proto-type galectins are in green, which are non-covalently connected. The chimera-type galectins are in yellow, which are self-associated with a c-terminal CRD and a non-carbohydrate bound n-terminal structural domain. The tandem repeat-type galectins are in blue, which are dimers consisting of a linker peptide joining two CRDs.

Figure 2

Galectin affects the function of immune cells at the maternal–fetal interface, maintaining maternal–fetal immunological tolerance. (1) Gal-1, regulated by estrogen, modulates HLA-G expression on EVT. (2) dNK cells produce gal-1, which can induce apoptosis of Th1 and Th17 cells. (3) Gal-3 induces the apoptosis of T cells. (4) Gal-13 and gal-14 can induce the apoptosis of T cells. (5) Gal-13 reduces the rate of apoptosis in neutrophils and increases the expression of PD-L1 and the production of HGF, TNF-$\alpha$, ROS and MMP-9 in neutrophils. (6) Gal-9 signal is important for the regulation of PBMC function toward a Th2 bias. (7) Gal-9 induce peripheral NK cells to a dNK-like phenotype. (8) Treg cells have high levels of gal-9, and gal-9 interacts with Tim-3 to promote the differentiation of decidual Tim-3+ CD4+ T cells into Treg cells.

Figure 3

Expression of galectins in four types of pregnancy-related diseases and their possible pathological mechanisms. The four pregnancy-related diseases are preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR) and preterm birth (PTB). The figure describes the dysregulation of galectins in these diseases. Red up-arrow means up regulation; Green down-arrow means down regulation.