Abstract
Improvement of endometrial receptivity is necessary for successful embryo implantation, and its impairment is associated with female infertility. In this study, we investigated the effect of the roots of Cnidium officinale Makino (CoM) on endometrial receptivity in both in vitro and in vivo model of embryo implantation. We found that CoM enhanced the adhesion of JAr cells to Ishikawa cells by stimulating expression of leukemia inhibitory factor (LIF) and integrins. In addition, blocking of LIFR using hLA or neutralization of integrins αV, β3, and β5 using antibodies significantly reduced the enhanced adhesion between JAr cell and CoM-treated Ishikawa cells, indicating that LIF and integrin play an important role in trophoblast-endometrium adhesion for embryo implantation. Furthermore, we identified that CoM significantly improved the implantation rate of blastocysts in the mouse model of RU-induced implantation failure. By collecting these results, here, we suggest that CoM has a therapeutic potential against female infertility associated with decreased endometrial receptivity.
Highlights
Embryonic implantation for a successful pregnancy is indispensable, which involves a complex process that requires molecular interactions of the endometrium and blastocyst [1]
leukemia inhibitory factor (LIF) binds with its receptor (LIFR) and the coreceptor glycoprotein 130, resulting in activation of downstream signaling through signal transducer and activator of transcription factor 3 (STAT3) [4, 5]
We showed a potential effect of Cnidium officinale Makino (CoM) on the enhancement of the endometrial receptivity. e molecular regulation underlying CoM-increased enhanced endometrial receptivity was related to the expression of LIF and integrin molecules
Summary
Embryonic implantation for a successful pregnancy is indispensable, which involves a complex process that requires molecular interactions of the endometrium and blastocyst [1]. During the window of implantation, the optimal environment of endometrium for adhering the embryo implies enhanced endometrial receptivity. E receptive endometrium is regulated by the interaction between hormones, growth factors, and cytokines [3]. Among cytokines in the endometrium, leukemia inhibitory factor (LIF) plays an important role in embryo implantation and is attributed to endometrial receptivity. Among the adhesion molecules that are regulated by cytokines such as secreted LIF, integrins are essential proteins to establish the required physical interaction between endometrium and blastocyst at the time of implantation. Like a LIF, the expression of integrins is used as a marker of endometrial receptivity [7, 8]
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