Greening David W, Nguyen Hong P T, Elgass Kirstin, Simpson Richard J, Salamonsen Lois A
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia
Hudson Institute of Medical Research (previously Prince Henry's Institute), Clayton, Victoria, Australia
Biol Reprod. 2016 Feb;94(2):38. doi: 10.1095/biolreprod.115.134890. Epub 2016 Jan 13.
Embryo implantation into receptive endometrium requires synergistic endometrial-blastocyst interactions within the uterine cavity and is essential for establishing pregnancy. We demonstrate that exosomes (40-150 nm nanovesicles) released from endometrial epithelial cells are an important component of these interactions. We defined the proteome of purified endometrial epithelial-derived exosomes (Exos) influenced by menstrual cycle hormones estrogen (E; proliferative phase) and estrogen plus progesterone (EP; receptive phase) and examined their potential to modify trophoblast function. E-/EP-Exos were uniquely enriched with 254 and 126 proteins, respectively, with 35% newly identified proteins not previously reported in exosome databases. Importantly, EP-Exos protein cargo was related to fundamental changes in implantation: adhesion, migration, invasion, and extracellular matrix remodeling. These findings from hormonally treated ECC1 endometrial cancer cells were validated in human primary uterine epithelial cell-derived exosomes. Functionally, exosomes were internalized by human trophoblast cells and enhanced their adhesive capacity, a response mediated partially through active focal adhesion kinase (FAK) signaling. Thus, exosomes contribute to the endometrial-embryo interactions within the human uterine microenvironment essential for successful implantation.
胚胎植入到具有接受性的子宫内膜需要子宫腔内子宫内膜与囊胚之间的协同相互作用，这对于建立妊娠至关重要。我们证明，子宫内膜上皮细胞释放的外泌体（40 - 150纳米的纳米囊泡）是这些相互作用的重要组成部分。我们定义了受月经周期激素雌激素（E；增殖期）和雌激素加孕激素（EP；接受期）影响的纯化子宫内膜上皮来源外泌体（Exos）的蛋白质组，并研究了它们改变滋养层细胞功能的潜力。E - /EP - Exos分别独特地富集了254种和126种蛋白质，其中35%的新鉴定蛋白质以前未在外泌体数据库中报道。重要的是，EP - Exos的蛋白质成分与植入过程中的基本变化有关：黏附、迁移、侵袭和细胞外基质重塑。这些来自经激素处理的ECC1子宫内膜癌细胞的发现，在人原代子宫上皮细胞来源的外泌体中得到了验证。在功能上，外泌体被人滋养层细胞内化，并增强了它们的黏附能力，这种反应部分是通过活跃的黏着斑激酶（FAK）信号介导的。因此，外泌体有助于人类子宫微环境中对成功植入至关重要的子宫内膜 - 胚胎相互作用。
