Expression and Localization of Galectin-9 in the Human Uterodome

Abstract

Abstract. Galectin-9 has been recently considered as a novel marker for the mid-and late-secretory phases of human endometrium and decidua. The aim of this study was to investigate the subcellular distribution of galectin-9 in the endometrial epithelium, especially during the frame of the implantation window. Endometrial biopsies in the proliferative, early, and mid-secretory phases from women with regular menstrual cycle were studied using several approaches, including scanning electron microscopy, immunostaining for light and transmission electron microscopies (TEM), immunoblotting, and statistical analysis of the area-related numerical densities of galectin-9-bound nanogold. Images of immunostaining for light microscopy demonstrated a strong expression of galectin-9 at the luminal and glandular endometrial epithelium in the mid-secretory phase compared to the proliferative and early secretory phases. Data of immunoblotting revealed a molecular weight of 36 kDa band with high intensity in the mid-secretory samples. Photomicrographs of immunogold staining for TEM illustrated the localization of galectin-9 in the uterodomes. Statistical and morphometric analysis showed a significantly higher area-related numerical density of galectin-9-bound nano-golds in the uterodomes compared to that of the uterodome-free areas of the luminal epithelium (p<0.001). This is the first demonstration of the molecular localization of galectin-9 in the bulbous ultrastructure of the human endometrial epithelium, called uterodomes. High expression of galectin-9 at uterodomes during the frame of implantation window suggests that galectin-9 can be considered as a marker of endometrial receptivity and should play an important role during the initial events of human embryo implantation.

Endometrial expression of progesterone-induced blocking factor and galectins-1, -3, -9, and -3 binding protein in the luteal phase and early pregnancy in cattle

“…This is similar to observations in humans (41), and the distinct expression of LGALS9 during the window of implantation has been suggested to play a potential role during embryo implantation (48). One of the characteristic processes of implantation is immunomodulation, which is characterized by an influx of immune cells at the implantation site (49).…”

“…In the current study, we showed that LGALS9 was only expressed in the epithelial cells, which is similar to the localization pattern of LGALS15 in the ovine endometrium (31). Although an integrin ligand for LGALS9 has yet to be identified (48), signaling through integrins may be one of the ways in which LGALS9 may function in cattle to mediate the process of implantation.…”

“…LGALS9 mediates cell adhesion and chemotaxis (42,57) and is thought to be one of the processes by which LGALS9 regulates leukocytes within the endometrium (48). A study in TK-1 cells showed that LGALS9 contributes to a TH2 cytokine bias by binding to Tim-3, a membrane protein expressed on the surface of fully differentiated TH1 cells, which negatively regulates TH1 responses (59), hence promoting a pregnancy protective effect.…”

“…LGALS1 in humans (56), mice (6), and cattle (34,36), galectin-3 (LGALS3) in humans (56), galectin-3 binding protein (LGALS3BP) in cattle (2), and galectin-9 (LGALS9) in humans (41,48) and cattle (2) are expressed in the uterine endometrium. An additional member of the galectin family, galectin 15 (LGALS15), was identified in the bovine, ovine, and caprine genome (31).…”

Peripheral Blood TIM-3 Positive NK and CD8+ T Cells throughout Pregnancy: TIM-3/Galectin-9 Interaction and Its Possible Role during Pregnancy

“…Supporting a reproductive role for Gal-9, M von Wolff et al and Popovici et al found that human endometrium and decidua express Gal-9 and it’s strong expression suggest a potential role during implantation [19]–[21]. In this regard, it is possible that TIM-3/Gal-9 interaction could play an important role in the regulation of maternal immune tolerance toward the fetus and may be a potent regulator of the adaptive and innate immune responses.…”