The Maternal-Fetal Interface in Small-for-Gestational-Age Pregnancies Is Associated With a Reduced Quantity of Human Decidual NK Cells With Weaker Functional Ability.
The Maternal-Fetal Interface in Small-for-Gestational-Age Pregnancies Is Associated With a Reduced Quantity of Human Decidual NK Cells With Weaker Functional Ability.
复制标题
DOI：
10.3389/fcell.2020.00633
复制
发表时间：
2020
影响因子：
5.5
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Lin F;Yang C;Feng T;Yang S;Zhou R;Li H
小于胎龄（SGA）是指出生体重小于相同胎龄婴儿平均体重的10%。这种情况与各种并发症有关，成年后患心脑血管疾病的风险很高。在正常妊娠或流产方面，母胎界面的蜕膜自然杀伤细胞（dNK）受到了重要的研究关注；然而，关于SGA的数据是有限的。在本研究中，我们旨在探讨dNK细胞在SGA中母胎界面的特征和调节作用。通过免疫荧光分析，我们发现dNK细胞与绒毛外滋养细胞保持密切接触，并且SGA中dNK细胞的比例比胎龄（AGA）减少更多。流式细胞术还显示，SGA组织中dNK细胞的比例（25.01±2.43%）明显低于AGA组织（34.25±2.30%）（p = 0.0103）。抑制受体NKG2A在dNK细胞上的表达以及dNK细胞中穿孔素和TGF-β1的分泌水平在SGA组明显高于AGA组，而dNK细胞在SGA组对K562细胞的细胞毒性减弱。与AGA相比，SGA中dNK细胞在促进滋养细胞或血管内皮细胞增殖、迁移、侵袭和成管方面的功能能力明显受损。dNK细胞功能异常可能影响胎儿生长发育，参与SGA的发病机制。
Small for gestational age (SGA) refers to a birth weight that is less than the 10th percentile of the mean weight of infants at the same gestational age. This condition is associated with a variety of complications, and a high risk of cardiovascular and cerebrovascular diseases in adulthood. Decidual natural killer (dNK) cells at the maternal–fetal interface have received significant research attention in terms of normal pregnancy or miscarriage; however, data relating to SGA are limited. In this study, we aimed to investigate the characteristics and regulatory role of dNK cells at the maternal–fetal interface in SGA. Using immunofluorescence assays, we found that dNK cells maintained close contact with extra-villous trophoblasts, and the proportion of dNK cells in SGA decreased more than in appropriate for gestational age (AGA). Flow cytometry also showed that there was a significantly lower percentage of dNK cells in SGA (25.01 ± 2.43%) than in AGA (34.25 ± 2.30%) (p = 0.0103). The expression of the inhibitory receptor NKG2A on dNK cells and the secretion levels of both perforin and TGF-β1 from dNK cells were significantly higher in SGA than in AGA, while the cytotoxicity of dNK cells in SGA against K562 cells was attenuated. Compared to AGA, the functional ability of dNK cells in SGA showed significant functional impairment in promoting proliferation, migration, invasion, and tube formation in trophoblast cells or vascular endothelial cells. The abnormal function of dNK cells may affect fetal growth and development, and could therefore participate in the pathogenesis of SGA.