Institut for Clinical Biochemistry and.
Institut for Molecular Biology, Hannover Medical School, Hannover, Germany.
J Clin Invest. 2019 Jan 2;129(1):422-436. doi: 10.1172/JCI99945. Epub 2018 Dec 10.
The negatively charged sugar sialic acid (Sia) occupies the outermost position in the bulk of cell surface glycans. Lack of sialylated glycans due to genetic ablation of the Sia-activating enzyme CMP-sialic acid synthase (CMAS) resulted in embryonic lethality around day 9.5 post coitum (E9.5) in mice. Developmental failure was caused by complement activation on trophoblasts in Cmas-/- implants and was accompanied by infiltration of maternal neutrophils at the fetal-maternal interface, intrauterine growth restriction, impaired placental development, and a thickened Reichert's membrane. This phenotype, which shared features with complement receptor 1-related protein Y (Crry) depletion, was rescued in E8.5 Cmas-/- mice upon injection of cobra venom factor, resulting in exhaustion of the maternal complement component C3. Here we show that Sia is dispensable for early development of the embryo proper but pivotal for fetal-maternal immune homeostasis during pregnancy, i.e., for protecting the allograft implant against attack by the maternal innate immune system. Finally, embryos devoid of cell surface sialylation suffered from malnutrition due to inadequate placentation as a secondary effect.
带负电荷的糖唾液酸（Sia）占据细胞表面聚糖的最外层位置。由于 CMP-唾液酸合酶（CMAS）的基因缺失导致唾液酸化聚糖的缺乏，导致小鼠在受精后第 9.5 天（E9.5）左右胚胎致死。Cmas-/-植入物中的滋养层补体激活导致发育失败，并伴有母体内皮细胞在胎儿-母体界面浸润、宫内生长受限、胎盘发育不良和 Reichert 膜增厚。这种表型与补体受体 1 相关蛋白 Y（Crry）耗竭的特征相似，在 E8.5 Cmas-/-小鼠中注射眼镜蛇毒液因子后得到挽救，导致母体补体成分 C3 耗尽。本文显示，Sia 对于胚胎的早期发育不是必需的，但对于妊娠期间胎儿-母体免疫稳态至关重要，即保护同种异体移植物免受母体固有免疫系统的攻击。最后，由于胎盘形成不足作为继发效应，缺乏细胞表面唾液酸化的胚胎由于营养不良而受苦。
