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PLoS One. 2016 Feb 3;11(2):e0148232. doi: 10.1371/journal.pone.0148232. eCollection 2016.

Paeonia lactiflora Enhances the Adhesion of Trophoblast to the Endometrium via Induction of Leukemia Inhibitory Factor Expression.

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Department of Korean Medical Science, School of Korean Medicine and Korean Medicine Research Center for Healthy Aging, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
Department of Obstetrics & Gynecology, Pusan National University Hospital, Pusan, Republic of Korea.
Department of Korean Obstetrics & Gynecology, School of Korean Medicine, Pusan National University, Pusan, Republic of Korea.
Laboratory of Molecular Toxicology, School of Pharmacy, SungKyunKwan University, Suwon, Gyeonggi-do, Republic of Korea.
Laboratory for Vascular Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
Department of Food Science and Technology, Keimyung University, Daegu, Republic of Korea.
Department of Clinical Pathology, TaeKyeung University, Gyeongsan, Republic of Korea.
Daechubatbaek Korean Medical Clinic, Gyeongju, Gyeongsangbuk-do, Republic of Korea.


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.

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