Priority Research Center, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, 35365, Republic of Korea.
Department of Anatomy, College of Medicine, Konyang University, Daejeon, 35365, Republic of Korea.
BMC Complement Med Ther. 2020 Feb 5;20(1):36. doi: 10.1186/s12906-020-2822-z.
Embryo implantation is essential for a successful pregnancy, and an elaborate synchronization between the receptive endometrium and trophoblast is required to achieve this implantation. To increase 'endometrial receptivity', the endometrium undergoes transformation processes including responses of adhesion molecules and cellular and molecular cell to cell communication. Many natural substances from traditional herbs have been studied to aid in the achievement of successful implantation. In this study, we investigated positive effects on embryonic implantation with decursinol that is a major compound extracted from Angelica gigas Nakai known to be associated with promotion of healthy pregnancy in the traditional Korean herbal medicine.
Expression of cell adhesion molecules after treatment of endometrial epithelial cells by decursinol (40 or 80 μM) was determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot analysis. The alteration of endometrial receptivity by decursinol (40 or 80 μM) was identified with the in vitro implantation model between Ishikawa cells and JAr cell spheroids (diameter, 143 ± 16 μm). Exosomes secreted from Ishikawa cells after treatment of 80 μM decursinol or dimethyl sulfoxide (DMSO) as the vehicle were investigated with invasion of JAr cells and attachment of JAr spheroids to Ishikawa cells.
Decursinol significantly (P < 0.05) increased the expression of important endometrial adhesion molecules such as integrin β1, β3, β5 and L-selectin mRNAs and integrin β5 and L-selectin in protein. The adhesion rate of JAr spheroids to decursinol-treated Ishikawa cells also increased significantly which was 2.4-fold higher than that of the control (P < 0.05). Furthermore, decursinol induced an increase in the release of exosomes from Ishikawa cells and decursinol-induced exosomes showed autocrine (to Ishikawa cells) and paracrine (to JAr cells) positive effects on our implantation model.
These results propose that decursinol could serve as a new and alternative solution for patients who are infertile.
胚胎着床对于成功妊娠至关重要，需要接受性子宫内膜和滋养层之间进行精细的同步化才能实现着床。为了提高“子宫内膜容受性”，子宫内膜会经历包括黏附分子以及细胞和分子间细胞通讯应答等转化过程。许多来自传统草药的天然物质已被研究用于辅助实现成功着床。在这项研究中，我们研究了当归醇这一主要化合物对胚胎着床的积极影响。当归醇是从当归中提取的，传统韩医学认为当归能促进健康妊娠。
通过定量逆转录聚合酶链反应（qRT-PCR）和 Western blot 分析，检测当归醇（40 或 80 μM）处理子宫内膜上皮细胞后细胞黏附分子的表达。通过 Ishikawa 细胞与 JAr 细胞球体（直径 143 ± 16 μm）之间的体外着床模型，鉴定当归醇（40 或 80 μM）对子宫内膜容受性的改变。用 80 μM 当归醇或二甲基亚砜（DMSO）处理后 Ishikawa 细胞分泌的外泌体，研究其对 JAr 细胞侵袭和 JAr 球体附着到 Ishikawa 细胞的影响。
当归醇显著（P<0.05）增加了重要的子宫内膜黏附分子如整合素β1、β3、β5 和 L-选择素 mRNA 和整合素β5 和 L-选择素的蛋白表达。JAr 球体与经当归醇处理的 Ishikawa 细胞的黏附率也显著增加，比对照组高 2.4 倍（P<0.05）。此外，当归醇诱导 Ishikawa 细胞中外泌体的释放增加，当归醇诱导的外泌体对我们的着床模型表现出自分泌（对 Ishikawa 细胞）和旁分泌（对 JAr 细胞）的积极作用。
这些结果表明，当归醇可以为不孕患者提供一种新的替代解决方案。
