1208-P: Role of Galectin-9 in the Development of Gestational Diabetes Mellitus (GDM)

Introduction: Interactions between the trophoblast and NK cells is critical for the regulation of inflammation in placenta. Galectin-9 (Gal-9) induces apoptosis of Th1 and NK cells. Since Gal-9 is highly expressed in placenta, we aimed to investigate the role of Gal-9 in the development of GDM.

Methods: C57BL/6J (WT) and B6-Lgals9^tm1glp (KO) female mice were assigned to standard fat diet (SFD) and high fat diet (HFD) and they were mated with WT and samples were obtained at gestational day 19. In the women with GDM, plasma at 2nd, 3rd trimester and after delivery, and placenta tissues were obtained. Mann-Whitney’s U test, one-way ANOVA with Tukey test, and Spearman correlation coefficient were used (IBM SPSS 23 and GraphPad Prism 10).

Results: In pregnant KO mice fed with HFD, the body weight was reduced compared to WT mice. Glucose tolerance tests demonstrated that blood glucose levels at 120 min were significantly higher (224 ± 22.5 mg/dL) compared to WT mice (199 ± 90.3 mg/dL) (P=0.032). The embryos from KO mice demonstrated macrosomia (1.30 ± 0.2 g) in comparison with WT mice (0.96 ± 0.2 g) (P=0.039). Gal-9 mRNA expression was upregulated in placenta from WT mice fed with HFD and Gal-9 was highly expressed in labyrinth layer. In placenta derived from KO mice fed with HFD, the number of apoptotic cells by TUNEL assay were reduced, while M1 and M2 macrophage, and NK cell markers were increased compared to WT mice. The women with GDM, plasma Gal-9 levels rapidly increased at 3rd trimester (2.01 ± 0.92 ng/mL) and immediately declined after birth (1.16 ± 0.48 ng/mL) (P=0.004). Plasma Gal-9 levels demonstrated negative correlation with HDL-C and LDL-C, and positive correlation with fasting plasma glucose and IRI.

Conclusions: Gal-9 deficiency promoted the development of GDM and Gal-9 may be involved in the maternal immune tolerance and suppression of the inflammatory process in placenta.