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Abstract
In the present study, we investigated the role of Paeonia lactiflora Pall. extract on embryo implantation in vitro and in vivo. A polysaccharides depleted-water extract of P. lactiflora (PL-PP) increased LIF expression in human endometrial Ishikawa cells at non-cytotoxic doses. PL-PP significantly increased the adhesion of the human trophectoderm-derived JAr spheroids to endometrial Ishikawa cells. PL-PP-induced LIF expression was decreased in the presence of a p38 kinase inhibitor SB203580 and an MEK/ERK inhibitor U0126. Furthermore, endometrial LIF knockdown by shRNA reduced the expression of integrins β3 and β5 and adhesion of JAr spheroids to Ishikawa cells. In vivo administration of PL-PP restored the implantation of mouse blastocysts in a mifepristone-induced implantation failure mice model. Our results demonstrate that PL-PP increases LIF expression via the p38 and MEK/ERK pathways and favors trophoblast adhesion to endometrial cells.
Highlights
Implantation is a complex biological process, requiring communication between the appropriately developed trophoblast and the receptive endometrium [1]
Our results demonstrate that PL-PP increases leukemia inhibitory factor (LIF) expression via the p38 and MEK/extracellular signal-regulated kinase (ERK) pathways and favors trophoblast adhesion to endometrial cells
Treatment with 10, 50, 100, and 500 μg/mL PL-WE showed 8, 22, 31, and 63% inhibition, respectively, while PL-PP treatment at concentrations of 500 μg/mL inhibited cell proliferation by 21% (S2B Fig)
Summary
Implantation is a complex biological process, requiring communication between the appropriately developed trophoblast and the receptive endometrium [1]. This process is established and maintained by diverse biological factors, including cytokines, growth factors, and receptors [2]. Embryo implantation is adversely affected by abnormal expression of the genes related to the establishment of uterine receptivity [3]. Among these factors, leukemia inhibitory factor (LIF) plays a key role in determining the outcome of implantation [4,5,6]. Inhibition of LIF activity by addition of an anti-LIF antibody or LIF antagonist effectively prevents embryo implantation in mice, monkeys, and humans [9,10,11,12]
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