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Exosomes and soluble secretome from hormone-treated endometrial epithelial cells direct embryo implantation.
Molecular Human Reproduction ( IF 4 ) Pub Date : 2020-05-13 , DOI: 10.1093/molehr/gaaa034 S Gurung 1 , D W Greening 2, 3 , S Catt 4 , L Salamonsen 1, 5 , J Evans 1, 6
Molecular Human Reproduction ( IF 4 ) Pub Date : 2020-05-13 , DOI: 10.1093/molehr/gaaa034 S Gurung 1 , D W Greening 2, 3 , S Catt 4 , L Salamonsen 1, 5 , J Evans 1, 6
Affiliation
A successful pregnancy requires a synchronous dialogue between endometrium and embryo within the endometrial milieu. The aim of this study was to assess the role in the implantation of mediators in the endometrial milieu. Total secretome (TS), soluble secretome (SS) and small extracellular vesicles (containing exosomes) were generated from hormonally primed human endometrial epithelial cell culture medium. Human trophectoderm stem cell-derived spheroids were cultured with TS, SS or exosomes (30 µg/ml) on hormonally primed epithelial cells, with exosomes significantly increasing cell adhesion and outgrowth. Furthermore, F1 mouse 2-cell embryos were cultured in groups for 48 h followed by culture with each secretome fraction (30 µg/ml) for 48 h. Blastocyst cell number and hatching were quantified. In addition, blastocysts were further cultured on a fibronectin matrix for 72 h or transferred to recipient mice (with corresponding secretomes) with embryo implantation assessed after 6 days. Exosomes significantly increased total cell number in mouse embryos and complete hatching from zona pellucida, with both exosomes and SS significantly enhancing mouse embryo outgrowth. Importantly, exosomes increased the embryo implantation rate in comparison to other secretome fractions (normalized based on treatment amount) from the endometrial epithelia. These data indicate that endometrial epithelial exosomes support embryo growth, development and implantation while the SS has selective involvement specifically on mouse embryo outgrowth. This finding provides new insights into the molecular differences of endometrial secretome components in implantation and early embryo development and may implicate endometrial exosomes in the pathophysiology of implantation failure in infertility.
中文翻译:
来自激素处理的子宫内膜上皮细胞的外泌体和可溶性分泌体指导胚胎植入。
成功怀孕需要子宫内膜环境中子宫内膜和胚胎之间的同步对话。本研究的目的是评估介质在子宫内膜环境中植入的作用。总分泌组 (TS)、可溶性分泌组 (SS) 和小的细胞外囊泡(含有外泌体)由激素引发的人子宫内膜上皮细胞培养基产生。人类滋养外胚层干细胞衍生的球体与 TS、SS 或外泌体 (30 µg/ml) 在激素引发的上皮细胞上培养,外泌体显着增加细胞粘附和生长。此外,F1 小鼠 2 细胞胚胎成组培养 48 小时,然后用每种分泌组份 (30 µg/ml) 培养 48 小时。对囊胚细胞数和孵化进行量化。此外,囊胚在纤连蛋白基质上进一步培养 72 小时或转移到受体小鼠(具有相应的分泌组),并在 6 天后评估胚胎植入。外泌体显着增加了小鼠胚胎的总细胞数和透明带的完全孵化,外泌体和 SS 都显着增强了小鼠胚胎的生长。重要的是,与来自子宫内膜上皮的其他分泌组分(根据治疗量标准化)相比,外泌体提高了胚胎着床率。这些数据表明,子宫内膜上皮外泌体支持胚胎生长、发育和着床,而 SS 选择性地参与小鼠胚胎的生长。
更新日期:2020-07-13
中文翻译:
来自激素处理的子宫内膜上皮细胞的外泌体和可溶性分泌体指导胚胎植入。
成功怀孕需要子宫内膜环境中子宫内膜和胚胎之间的同步对话。本研究的目的是评估介质在子宫内膜环境中植入的作用。总分泌组 (TS)、可溶性分泌组 (SS) 和小的细胞外囊泡(含有外泌体)由激素引发的人子宫内膜上皮细胞培养基产生。人类滋养外胚层干细胞衍生的球体与 TS、SS 或外泌体 (30 µg/ml) 在激素引发的上皮细胞上培养,外泌体显着增加细胞粘附和生长。此外,F1 小鼠 2 细胞胚胎成组培养 48 小时,然后用每种分泌组份 (30 µg/ml) 培养 48 小时。对囊胚细胞数和孵化进行量化。此外,囊胚在纤连蛋白基质上进一步培养 72 小时或转移到受体小鼠(具有相应的分泌组),并在 6 天后评估胚胎植入。外泌体显着增加了小鼠胚胎的总细胞数和透明带的完全孵化,外泌体和 SS 都显着增强了小鼠胚胎的生长。重要的是,与来自子宫内膜上皮的其他分泌组分(根据治疗量标准化)相比,外泌体提高了胚胎着床率。这些数据表明,子宫内膜上皮外泌体支持胚胎生长、发育和着床,而 SS 选择性地参与小鼠胚胎的生长。