The chimera‐type galectin‐3 is a positive modulator of trophoblast functions with dysregulated expression in gestational diabetes mellitus

Abstract

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Novel Biomolecules in the Pathogenesis of Gestational Diabetes Mellitus

“…Its expression has been demonstrated in many cell types, including neutrophils, macrophages, mast cells, fibroblasts, and osteoclasts. It is modulated by estrogens and progesterone [ 35 ]. Increased levels of galectin 3 favor the development of insulin resistance.…”

Galectins in Early Pregnancy and Pregnancy-Associated Pathologies

“…Attenuation of endogenous galectin-3 (by siRNA) led to a significant decrease in HTR-8/SVneo cell invasion, accompanied by decline in integrin β1 and matrix metalloproteinases (MMP)-2 and -9 [52]. Freitag and colleagues obtained similar results for HIPEC-65 cells, a CTB cell line, whose invasion was stimulated by rhgal-3, as well [54]. Moreover, exogenous galectin-3 enhanced the tube formation capacity of the EVT cell line SGHPL-4 [54].…”

“…Galectin-1 stimulates first-trimester cytotrophoblast, HTR-8/SVneo and JAR cell invasion [41,42] Galectin-1 decreases BeWo cell proliferation [43] Galectin-1 modulates HLA-G expression on trophoblast cells, suggesting its role in immune tolerance [44] Galectin-1 stimulates syncytialization of BeWo cells but decreases human chorionic gonadotropin and progesterone production [45,47] Galectin-3 stimulates HTR-8/SVneo cell migration and HTR-8/SVneo cell, first-trimester CTB and HIPEC-65 cell invasion [52,54] Galectin-3 increases endothelial-like properties of EVT cell line SGHPL-4 [54] Galectin-3 stimulates syncytialization of BeWo cells [54] Galectin-7 decreases first-trimester trophoblast cells' and HTR-8/SVneo cells' capacity to adhere to endometrial epithelial cells and first-trimester EVT outgrowth from placental explants [16,57] Galectin-9 derived from trophoblast cells promotes immune tolerance at the feto-maternal interface [58][59][60] Galectin-9 inhibits the apoptosis and proinflammatory cytokine production of HTR-8/SVneo cells and increases the interaction with endothelium in a JNK-dependent manner [61] Galectin-13 induces apoptosis of activated T cells in vitro, diverts and kills T cells and macrophages in the maternal decidua and polarizes neutrophils towards permissive phenotype for placental growth [62,63] Galectin-13 may induce angiogenesis at the feto-maternal interface [6] Galectin-14 promotes trophoblast cell migration and invasion by stimulating the expression of MMP-9 and N-cadherin through Akt phosphorylation [64] Galectin-14 may function in angiogenesis [6] Pregnancy loss Galectin-1 is significantly lower in placenta tissue after miscarriage and RPL [65,66] Galectin-2 is downregulated in VT and EVT after SA and RPL [66] Maternal deficiency of galectin-3 is associated with structural alterations in placenta, with reduced trophoblast layers and a corresponding enlarged maternal decidua. The absence of galectin-3 also results in reduced total vessel length and vessel area, suggesting placental malperfusion.…”

Medawar’s PostEra: Galectins Emerged as Key Players During Fetal-Maternal Glycoimmune Adaptation

“…Despite considerable research over the past years, the functional implications of gal-3 in the context of pregnancy are only just emerging. In humans, gal-3 mRNA and protein can be detected in maternal decidual cells ( 86 ) and also in all trophoblast lineages of the placenta ( 87 ), with increased expression levels associated with differentiation of the cytotrophoblasts along the invasive extravillous trophoblast pathway ( 87 , 88 ). In line with these findings, recent in vitro studies have identified gal-3 as part of the trophoblast invasion machinery ( 89 ) as well as a positive modulator of crucial trophoblast cell functions including capillary tube formation and syncytialization ( 88 ).…”

“…In humans, gal-3 mRNA and protein can be detected in maternal decidual cells ( 86 ) and also in all trophoblast lineages of the placenta ( 87 ), with increased expression levels associated with differentiation of the cytotrophoblasts along the invasive extravillous trophoblast pathway ( 87 , 88 ). In line with these findings, recent in vitro studies have identified gal-3 as part of the trophoblast invasion machinery ( 89 ) as well as a positive modulator of crucial trophoblast cell functions including capillary tube formation and syncytialization ( 88 ). In mice, gal-3 is detected primarily in the uterine luminal and glandular epithelium, where its timely up-regulation appears to be a requisite for successful implantation ( 90 ).…”