Galectin-1 influences trophoblast immune evasion and emerges as a predictive factor for the outcome of pregnancy

Abstract

Galectin-1 (gal-1) is expressed at the feto-maternal interface and plays a role in regulating the maternal immune response against placental alloantigens, contributing to pregnancy maintenance. Both decidua and placenta contribute to gal-1 expression and may be important for the maternal immune regulation. The expression of gal-1 within the placenta is considered relevant to cell-adhesion and invasion of trophoblasts, but the role of gal-1 in the immune evasion machinery exhibited by trophoblast cells remains to be elucidated. In this study, we analyzed gal-1 expression in preimplantation human embryos and first-trimester decidua-placenta specimens and serum gal-1 levels to investigate the physiological role played by this lectin during pregnancy. The effect on human leukocyte antigen G (HLA-G) expression in response to stimulation or silencing of gal-1 was also determined in the human invasive, proliferative extravillous cytotrophoblast 65 (HIPEC65) cell line. Compared with normal pregnant women, circulating gal-1 levels were significantly decreased in patients who subsequently suffered a miscarriage. Human embryos undergoing preimplantation development expressed gal-1 on the trophectoderm and inner cell mass. Furthermore, our in vitro experiments showed that exogenous gal-1 positively regulated the membrane-bound HLA-G isoforms (HLA-G1 and G2) in HIPEC65 cells, whereas endogenous gal-1 also induced expression of the soluble isoforms (HLA-G5 and -G6). Our results suggest that gal-1 plays a key role in pregnancy maternal immune regulation by modulating HLA-G expression on trophoblast cells. Circulating gal-1 levels could serve as a predictive factor for pregnancy success in early human gestation.

Interfering with Gal-1–mediated angiogenesis contributes to the pathogenesis of preeclampsia

“…Furthermore, recent studies have demonstrated that Gal-1 regulates trophoblast invasion, differentiation, and immunomodulatory functions (such as HLA-G expression) in vitro (10,13,14). Therefore, it is attractive to speculate that defective Gal-1 expression contributes to the impaired placentation and vascular abnormalities observed in anginex-treated or Lgals1 KO placentas.…”

“…(ii) prevent a normal placentation (10,13,14), (iii) abrogate maternal immune tolerance toward fetal antigens (11,12), and (iv) threaten gestation by favoring the development of PE, implying that Gal-1 function is essential for a healthy gestation. Anomalies in Gal-1 circulating levels or alteration of Gal-1 expression in the placental villi have been associated with the physiopathology of early pregnancy loss (10,31).…”

“…Anomalies in Gal-1 circulating levels or alteration of Gal-1 expression in the placental villi have been associated with the physiopathology of early pregnancy loss (10,31). In addition, we have recently identified a reduced frequency of Gal-1 expressing T and natural killer (NK) cells in the peripheral blood of women with PE (32), which might contribute to the excessive inflammatory responses during the course of PE syndrome (33).…”

“…Circulating Gal-1 levels increase during the first trimester compared with nonpregnant women and reach a maximum in the second trimester, which is maintained until term (10). Gal-1 exerts important functions on the maternal immune tolerance toward the fetus by promoting tolerogenic dendritic cells (DC), IL-10 + regulatory T (Treg) cells (11), and the apoptosis of alloreactive T cells (12), as well as by regulating the expression of human leukocyte antigen-G (HLA-G) on trophoblasts during the early stages of human pregnancy (10). Of note, the invasion process that characterizes human placentation seems to be fine tuned by Gal-1 (13,14).…”

Extracellular presence/release of galectins from HTR-8/SVneo extravillous trophoblast cells*

“…It is of interest to note that EVT cell invasion is increased by both gal-1 (Kolundzic et al, 2011b) and EVs from cytotrophoblast cells grown in a hypoxic environment (Salomon et al, 2013). Both gal-1 (Blois et al, 2007;Tirado-Gonzalez et al, 2013) and placental EVs (Stenqvist et al, 2013;Mincheva-Nilsson and Baranov, 2014;Tannetta et al, 2014) are involved in immunoregulation during pregnancy. As for gal-3 and gal-8, their role in trophoblasts is still unresolved.…”