Abstract
BackgroundEmbryo 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.MethodsExpression 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.ResultsDecursinol 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.ConclusionThese results propose that decursinol could serve as a new and alternative solution for patients who are infertile.
Highlights
Embryo implantation is essential for a successful pregnancy, and an elaborate synchronization between the receptive endometrium and trophoblast is required to achieve this implantation
Effects of decursinol on the expression of endometrial receptivity markers Integrins, L-selectin, and E-cadherin are known as adhesion molecules expressed in human endometrial epithelial cells
To assess the effect of decursinol on the expression of these receptivity markers in endometrial epithelial cells, Ishikawa cells were treated with different concentrations of decursinol (40 μM and 80 μM) and the mRNA expression of receptivity markers measured via real-time qPCR
Summary
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. Under regulation by estrogen (E2) and progesterone (P4), the endometrium undergoes numerous transformation processes, including responses of adhesion molecules, cellular and molecular cell-cell communication, extracellular matrix (ECM) remodeling, and expression of many growth factors, cytokines, and their mediators [4]. Failure to establish endometrial receptivity is a major cause of recurrent implantation failure in women [6, 7]. To resolve this problem, assisted reproductive technologies (ART) have been steadily developed [8, 9]. Since traditional herbal remedies have been proven to be safe when administered orally, many researchers have focused on natural substances [13,14,15,16,17]; failure of implantation still remains the main challenge in the success of ART [8, 9]
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