Galectin-3 deficiency in pregnancy increases the risk of fetal growth restriction (FGR) via placental insufficiency
Galectin-3 deficiency in pregnancy increases the risk of fetal growth restriction (FGR) via placental insufficiency
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孕期缺乏半乳糖凝集素 - 3会通过胎盘功能不全增加胎儿生长受限（FGR）的风险。
DOI：
10.1038/s41419-020-02791-5
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发表时间：
2020-07-23
影响因子：
9
通讯作者：
Blois, Sandra M.
中科院分区：
文献类型：
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作者：
Freitag, Nancy;Tirado-Gonzalez, Irene;Blois, Sandra M.
胎儿生长受限（FGR）是发达国家最常见的妊娠并发症。受 FGR 影响的妊娠经常伴有并发症以及新生儿发病和死亡的高风险。迄今为止，尚无批准的治疗方法可用于患有 FGR 的孕妇。本研究的目的是探讨半乳糖凝集素 3 (gal-3) 的作用，半乳糖苷结合蛋白是一种 β-半乳糖苷结合蛋白，涉及妊娠、胎盘功能和胎儿生长。我们证明，小鼠怀孕期间缺乏 gal-3 会导致胎盘功能障碍，并在没有母体先兆子痫综合征的情况下促进 FGR。对 gal-3 缺陷母鼠的分析揭示了胎盘炎症和灌注不良，以及异常激活的子宫自然杀伤细胞浸润。我们的结果还表明，FGR 与人类妊娠中期和晚期妊娠循环中 gal-3 水平未能增加有关。受 FGR 影响的人类妊娠胎盘表现出较低的 gal-3 表达，这与胎盘功能障碍相关。这些数据强调了 gal-3 在促进正常胎盘功能中的重要性，因为它的缺失会导致胎盘疾病和随后的 FGR。
Fetal growth restriction (FGR) is the most common pregnancy complication in developed countries. Pregnancies affected by FGR, frequently concur with complications and high risk of neonatal morbidity and mortality. To date, no approved treatment is available for pregnant women affected with FGR. The objective of this study was to investigate the contribution of galectin-3 (gal-3), a beta -galactoside binding protein involved in pregnancy, placental function and fetal growth. We demonstrated that lack of gal-3 during mouse pregnancy leads to placental dysfunction and drives FGR in the absence of a maternal preeclampsia syndrome. Analysis of gal-3 deficient dams revealed placental inflammation and malperfusion, as well as uterine natural killer cell infiltration with aberrant activation. Our results also show that FGR is associated with a failure to increase maternal circulating gal-3 levels during the second and third trimester in human pregnancies. Placentas from human pregnancies affected by FGR displayed lower gal-3 expression, which correlated with placental dysfunction. These data highlight the importance of gal-3 in the promotion of proper placental function, as its absence leads to placental disease and subsequent FGR.