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

Hee-Jung Choi; Tae-Wook Chung; Mi-Ju Park; Kyu Sup Lee; Youngjin Yoon; Hyung Sik Kim; Jun Hee Lee; Sang-Mo Kwon; Syng-Ook Lee; Keuk-Jun Kim; Jin-Ho Baek; Ki-Tae Ha

doi:10.1371/journal.pone.0148232

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

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

Authors

Hee-Jung Choi¹, Tae-Wook Chung¹, Mi-Ju Park¹, Kyu Sup Lee², Youngjin Yoon³, Hyung Sik Kim⁴, Jun Hee Lee⁵, Sang-Mo Kwon⁵, Syng-Ook Lee⁶, Keuk-Jun Kim⁷, Jin-Ho Baek⁸, Ki-Tae Ha¹

Affiliations

¹ 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.
² Department of Obstetrics & Gynecology, Pusan National University Hospital, Pusan, Republic of Korea.
³ Department of Korean Obstetrics & Gynecology, School of Korean Medicine, Pusan National University, Pusan, Republic of Korea.
⁴ Laboratory of Molecular Toxicology, School of Pharmacy, SungKyunKwan University, Suwon, Gyeonggi-do, Republic of Korea.
⁵ 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.
⁶ Department of Food Science and Technology, Keimyung University, Daegu, Republic of Korea.
⁷ Department of Clinical Pathology, TaeKyeung University, Gyeongsan, Republic of Korea.
⁸ Daechubatbaek Korean Medical Clinic, Gyeongju, Gyeongsangbuk-do, Republic of Korea.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Butadienes / pharmacology
Cell Adhesion / drug effects
Cell Line, Tumor
Embryo Implantation / drug effects
Embryo Implantation / physiology*
Endometrium / metabolism*
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
Female
Humans
Imidazoles / pharmacology
Integrin beta3 / biosynthesis
Leukemia Inhibitory Factor / biosynthesis*
Leukemia Inhibitory Factor / genetics
Leukemia Inhibitory Factor / metabolism
Male
Mice
Mice, Inbred C57BL
Nitriles / pharmacology
Paeonia / metabolism*
Plant Extracts / pharmacology*
Pyridines / pharmacology
RNA Interference
RNA, Small Interfering / genetics
Trophoblasts / metabolism*
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors

Substances

Butadienes
Imidazoles
Integrin beta3
Leukemia Inhibitory Factor
Nitriles
Plant Extracts
Pyridines
RNA, Small Interfering
U 0126
Extracellular Signal-Regulated MAP Kinases
p38 Mitogen-Activated Protein Kinases
SB 203580

Grants and funding

This study was supported by a grant of the Traditional Korean Medicine R&D Project, Ministry of Health & Welfare (Grant no. HI13C0502), and by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT & Future Planning (MISP), Korea Government (Grant no. 2014R1A5A20009936).