Abstract
Despite advances in assisted reproductive technology, treatment for deficient endometrial receptivity is a major clinical unmet need. In our previous study, the water extract of Paeonia lactiflora Pall. enhanced endometrial receptivity in vitro and in vivo via induction of leukemia inhibitory factor (LIF), an interleukin (IL)-6 family cytokine. In the present study, we found that paeoniflorin, a monoterpene glycoside, is the major active compound of P. lactiflora. Paeoniflorin significantly improved the embryo implantation rate in a murine model of mifepristone (RU486)-induced implantation failure. In addition, paeoniflorin increased the adhesion of human trophectoderm-derived JAr cells to endometrial Ishikawa cells through the expression of LIF in vitro. Moreover, using the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database of the human endometrium, we confirmed that LIF signaling is a key regulator for improving human endometrial receptivity. Therefore, these results suggest that paeoniflorin might be a potent drug candidate for the treatment of endometrial implantation failure by enhancing endometrial receptivity.
Highlights
Our results showed that methyl gallate, paeoniflorin, and paeonol increased leukemia inhibitory factor (LIF) protein expression levels (Figure 1B)
The results demonstrated that paeoniflorin increased the expression of both messenger RNA and protein expression levels of LIF
We demonstrated that paeoniflorin enhanced endometrial receptivity in vivo and in vitro by expressing LIF, the detailed molecular mechanisms were not fully examined
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. A receptive endometrium is a crucial factor for successful pregnancy [1]. Despite advances in assisted reproductive technology (ART), the implantation success rates of transferred embryo have not sufficiently improved [2]. To evaluate and improve endometrial receptivity, vigorous studies, including on endometrial receptivity array and intentional endometrial injury, have been conducted [3,4]. There are very limited clinical options for improving endometrial receptivity [5]. More precise, comprehensive, and novel approaches for enhancing endometrial receptivity are needed
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