Department of Gynaecological Endocrinology and Reproductive Medicine, Medical University of Innsbruck, Anichstraße 35, Innsbruck, 6020, Austria.
Institute of Medical Biochemistry, Biochemical Immunotoxicology Group, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
Reprod Biol Endocrinol. 2024 Nov 23;22(1):150. doi: 10.1186/s12958-024-01319-2.
To study the crosstalk between maternal immune cells and the developing embryo by investigating the immunogenic properties of human blastocyst spent media (SM) on dendritic cells.
In this prospective multicenter experimental study, human preimplantation embryo spent media were collected after blastocyst formation, grouped based on successful or unsuccessful implantation, and analyzed by protein array or used to stimulate monocyte derived dendritic cells (moDC). The immunomodulatory properties of SM on moDC were investigated by analyzing changes in phenotype, cytokine secretion, indoleamine 2,3-dioxygenase (IDO) activity, and ability to activate T cells.
A plethora of cytokines and growth factors secreted from preimplantation embryos was detected. Exposure to embryo SM altered the phenotype of moDC in a manner dependent on the implantation outcome. Specifically, SM from non-implanted embryos increased the expression of co-stimulatory molecules and activation markers on moDC. Furthermore, SM treated dendritic cells secreted low levels of cytokines and growth factors and were able to stimulate naïve T cells. Activation of IDO was decreased in moDC after stimulation with SM.
Our findings show that human preimplantation embryos secrete an abundance of molecules with the ability to significantly affect and even regulate immune cells in their environment.
通过研究人类囊胚耗竭培养基（SM）对树突状细胞的免疫原性，研究母体免疫细胞与发育中的胚胎之间的串扰。
在这项前瞻性多中心实验研究中，在囊胚形成后收集人着床前胚胎耗竭培养基，根据成功或不成功的着床进行分组，并通过蛋白质阵列进行分析或用于刺激单核细胞衍生的树突状细胞（moDC）。通过分析表型、细胞因子分泌、吲哚胺 2,3-双加氧酶（IDO）活性和激活 T 细胞的能力，研究 SM 对 moDC 的免疫调节特性。
检测到大量来自着床前胚胎的细胞因子和生长因子。胚胎 SM 的暴露以依赖于着床结果的方式改变 moDC 的表型。具体而言，来自未着床胚胎的 SM 增加了 moDC 上共刺激分子和激活标记物的表达。此外，SM 处理的树突状细胞分泌低水平的细胞因子和生长因子，并能够刺激幼稚 T 细胞。SM 刺激后 moDC 中的 IDO 活性降低。
我们的研究结果表明，人类着床前胚胎分泌大量的分子，这些分子具有显著影响甚至调节其环境中免疫细胞的能力。
