<b>Role of galectin-9 in the development of gestational diabetes mellitus</b>

Galectin-9 (Gal-9) is highly expressed in trophoblasts in placenta. Interaction between Gal-9 and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) is important for the differentiation of tissue resident natural killer (trNK) cells in placenta and maintenance of normal pregnancy. Furthermore, the enhanced maternal systemic inflammation associated with increased proinflammatory cytokines in preeclampsia is mediated by enhanced interaction between Gal-9 and Tim-3. However, the role of Gal-9 in gestational diabetes (GDM) remains unexplored. Plasma Gal-9 levels were elevated at 3rd trimester in pregnant women with GDM and positively correlated with placenta and newborn weight. <i>Lgals9</i> knockout pregnant mice fed with high fat diet (HFD KO) demonstrated maternal glucose intolerance and fetus macrosomia compared with wild pregnant mice (HFD WT). In HFD KO, increased proliferating cells, reduced apoptosis, and autophagy impairment were observed in junctional zones. The number of trNK cells and percentage of Tim-3+ trNK increased, while early apoptosis percentage in Tim-3+ trNK was reduced in placenta of HFD KO. The elevation of plasma Gal-9 may be a biomarker for prediction of maternal glucose intolerance and fetal macrosomia in pregnant women with GDM and Gal-9 functions as a compensation factor for GDM by inducing apoptosis in Tim-3+ trNK cells.半乳糖凝集素9（Galectin-9，简称Gal-9）在胎盘滋养层细胞中呈高表达。Gal-9与T细胞免疫球蛋白黏蛋白域包含蛋白3（Tim-3）之间的相互作用，对于胎盘组织驻留自然杀伤细胞（trNK）的分化以及正常妊娠的维持具有重要意义。此外，子痫前期患者体内促炎细胞因子增多所介导的母体全身炎症反应增强，正是由Gal-9与Tim-3的相互作用加剧所驱动的。然而，Gal-9在妊娠期糖尿病（GDM）中的作用仍未得到深入研究。研究发现，妊娠期糖尿病患者妊娠第三孕期的血浆Gal-9水平显著升高，且与胎盘重量及新生儿体重呈正相关。与高脂饮食（HFD）喂养的野生型孕鼠（HFD WT）相比，高脂饮食喂养的<i>Lgals9</i>基因敲除孕鼠（HFD KO）表现出母体葡萄糖不耐受与胎儿巨大症。在HFD KO组的胎盘交界区中，可观察到增殖细胞数量增加、细胞凋亡减少以及自噬功能受损。同时，该组胎盘中的trNK细胞总数及Tim-3阳性trNK细胞占比均有所升高，而Tim-3阳性trNK细胞的早期凋亡率则显著降低。血浆Gal-9水平升高或可作为预测妊娠期糖尿病患者母体葡萄糖不耐受与胎儿巨大症的生物标志物；同时，Gal-9可通过诱导Tim-3阳性trNK细胞凋亡，充当妊娠期糖尿病的代偿调控因子。