Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Kreutzwaldi 62, Tartu, 51006, Estonia.
Department of Animal Science, Faculty of Agriculture, University of Peradeniya, Peradeniya, 20400, Sri Lanka.
Sci Rep. 2024 Oct 29;14(1):25911. doi: 10.1038/s41598-024-75893-1.
Successful embryo implantation relies on synchronized dialog between the embryo and endometrium, and the role of extracellular vesicles (EVs) in facilitating this cross-talk has been recently established. In our previous study, milk fat globule-EGF factor 8 protein (MFGE8) was identified as increasing in receptive endometrial epithelial cells (EECs) in response to trophoblastic EVs. However, the dynamics of MFGE8 protein in this context are not completely understood. Therefore, we examined its expression and secretion in EECs exposed to estrogen, progesterone, and trophoblastic EVs to gain deeper insights into its potential as an indicator of EV-mediated embryo-maternal dialogue. Our findings revealed that MFGE8 secretion is sensitive to estrogen and progesterone, and that trophoblastic EVs stimulate their release in both receptive and non-receptive EECs. Furthermore, trophoblast EV function was dose and time-dependent. Notably, the secretion of MFGE8 increased within a short timeframe of 30 min after addition of EVs, suggesting the possibility of rapid processes such as binding, fusion or internalization of trophoblastic EVs within EECs. Interestingly, MFGE8 released from EECs was associated with EVs, suggesting increased EV secretion from EECs in response to embryonic signals. In conclusion, increased MFGE8 secretion in this embryo implantation model can serve as an indicator of EV-mediated embryo-maternal dialogue.
胚胎着床的成功依赖于胚胎和子宫内膜之间的同步对话，而细胞外囊泡（EVs）在促进这种交流中的作用最近已经得到证实。在我们之前的研究中，发现牛奶脂肪球 EGF 因子 8 蛋白（MFGE8）在滋养层 EV 刺激下在接受性子宫内膜上皮细胞（EEC）中增加。然而，在这种情况下，MFGE8 蛋白的动态变化还不完全清楚。因此，我们研究了 EEC 暴露于雌激素、孕激素和滋养层 EV 时 MFGE8 蛋白的表达和分泌，以更深入地了解其作为 EV 介导的胚胎-母体对话指标的潜力。我们的研究结果表明，MFGE8 的分泌对雌激素和孕激素敏感，而滋养层 EV 刺激其在接受性和非接受性 EEC 中的释放。此外，滋养层 EV 的功能具有剂量和时间依赖性。值得注意的是，在添加 EV 后 30 分钟的短时间内，MFGE8 的分泌增加，这表明可能存在滋养层 EV 与 EEC 结合、融合或内化等快速过程。有趣的是，从 EEC 释放的 MFGE8 与 EV 相关，这表明 EEC 对胚胎信号的反应增加了 EV 的分泌。总之，在这个胚胎着床模型中，MFGE8 分泌的增加可以作为 EV 介导的胚胎-母体对话的指标。
