Water-extracted tubers of Cyperus rotundus L. enhance endometrial receptivity through leukemia inhibitory factor-mediated expression of integrin αVβ3 and αVβ5

被引:19
作者
Choi, Hee-Jung [1 ]
Chung, Tae-Wook [1 ]
Park, Mi-Ju [1 ]
Jung, Yeon-Seop [2 ]
Lee, Syng-Ook [2 ]
Kim, Keuk-Jun [3 ]
Ha, Ki-Tae [1 ]
机构
[1] Pusan Natl Univ, Sch Korean Med, Hlth Aging Korean Med Res Ctr, Busandaehak Ro 49, Yangsan 50612, Gyeongsangnam D, South Korea
[2] Keimyung Univ, Dept Food Sci & Technol, Daegu, South Korea
[3] DaeKyeung Univ, Dept Clin Pathol, Gyongsan, Gyeongsangbuk D, South Korea
基金
新加坡国家研究基金会;
关键词
Cyperus rotundus L; Endometrial receptivity; Leukemia inhibitory factor; Integrin; alpha V beta 3; alpha V beta 5; CHINESE HERBAL MEDICINE; EMBRYO IMPLANTATION; INFERTILITY; ADHESION; LIF;
D O I
10.1016/j.jep.2017.06.051
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Ethnopharmacological relevance: Cyperus rotundus L. (CR) has been traditionally used as an herbal medicine in Asian countries to treat diverse gynecological disorders. However, the potential therapeutic effect of CR on endometrial receptivity for successful embryo implantation to treat female infertility has not been fully studied. Aim of study: The aim of this study was to evaluate the effect of water-extracted CR on endometrial receptivity by investigating the expression of leukemia inhibitory factor (LIF) and integrins, cell adhesion, and embryo implantation using mifepristone (RU486; RU)-induced implantation failure model. Materials and methods: The water extract of CR was prepared and fingerprinted using high-performance liquid chromatography (HPLC). For the expression and regulation of LIF, reverse transcription polymerase chain reaction (RT-PCR) and western blotting were performed in CR-stimulated Ishikawa cells. To evaluate LIF-mediated integrin expression, knockdown of LIF by shRNA was performed in Ishikawa cells. The effect of CR on endometrial receptivity was determined by an in vitro adhesion assay between JAr cells and CR-induced Ishikawa cells. In vivo, C57BL/6 female mice (n = 7 per group) orally received CR (31.68 mg/kg/day), a similar dose as used clinically. Seven days after CR treatment, all female mice were caged with male mice until pregnancy was verified. On day 4 of pregnancy, RU (4 mg/kg) was injected subcutaneously to induce embryo implantation failure. Result: CR increased the expression of LIF through the phosphatidylinositol-3-kinase/ protein kinase B (PI-3K/AKT) signaling pathway in Ishikawa cells. In addition, CR enhanced adhesion of JAr cells onto Ishikawa cells by inducing the expression of LIF-dependent integrins alpha V beta 3 and alpha V beta 5. Furthermore, CR improved the number of implantation sites in pregnant mice despite RU injection. Conclusion: CR increased the expression of LIF-mediated integrins alpha V beta 3 and alpha V beta 5 on the surface of endometrial cells, which is associated with adhesion of trophoblastic cells to endometrial cells for blastocyst implantation. Our findings provide evidence that CR has therapeutic potential against poor endometrial receptivity.
引用
收藏
页码:16 / 23
页数:8
相关论文
共 27 条
  • [1] p38 MAPK signaling acts upstream of LIF-dependent neuroprotection during photoreceptor degeneration
    Agca, C.
    Gubler, A.
    Traber, G.
    Beck, C.
    Imsand, C.
    Ail, D.
    Caprara, C.
    Grimm, C.
    [J]. CELL DEATH & DISEASE, 2013, 4 : e785 - e785
  • [2] Leukemia inhibitory factor and human embryo implantation
    Aghajanova, L
    [J]. UTERUS AND HUMAN REPRODUCTION, 2004, 1034 : 176 - 183
  • [3] Embryo implantation: the molecular mechanism remains elusive
    Aplin, J. D.
    [J]. REPRODUCTIVE BIOMEDICINE ONLINE, 2006, 13 (06) : 833 - 839
  • [4] Cambie R.C., 1997, ANTIFERTILITY PLANTS
  • [5] Identifying Chinese herbal medicine for premenstrual syndrome: implications from a nationwide database
    Chen, Hsing-Yu
    Huang, Ben-Shian
    Lin, Yi-Hsuan
    Su, Irene H.
    Yang, Sien-Hung
    Chen, Jiun-Liang
    Huang, Jen-Wu
    Chen, Yu-Chun
    [J]. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE, 2014, 14
  • [6] Investigation on Chinese herbal medicine for primary dysmenorrhea: Implication from a nationwide prescription database in Taiwan
    Chen, Hsing-Yu
    Lin, Yi-Hsuan
    Su, Irene H.
    Chen, Yu-Chun
    Yang, Sien-hung
    Chen, Jiun-liang
    [J]. COMPLEMENTARY THERAPIES IN MEDICINE, 2014, 22 (01) : 116 - 125
  • [7] Paeonia lactiflora Enhances the Adhesion of Trophoblast to the Endometrium via Induction of Leukemia Inhibitory Factor Expression
    Choi, Hee-Jung
    Chung, Tae-Wook
    Park, Mi-Ju
    Lee, Kyu Sup
    Yoon, Youngjin
    Kim, Hyung Sik
    Lee, Jun Hee
    Kwon, Sang-Mo
    Lee, Syng-Ook
    Kim, Keuk-Jun
    Baek, Jin-Ho
    Ha, Ki-Tae
    [J]. PLOS ONE, 2016, 11 (02):
  • [8] Integrin αVβ3 and αVβ5 are required for leukemia inhibitory factor-mediated the adhesion of trophoblast cells to the endometrial cells
    Chung, Tae-Wook
    Park, Mi-Ju
    Kim, Hyung Sik
    Choi, Hee-Jung
    Ha, Ki-Tae
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2016, 469 (04) : 936 - 940
  • [9] Leukemia inhibitory factor (LIF) and LIF receptor expression in human endometrium suggests a potential autocrine paracrine function in regulating embryo implantation
    Cullinan, EB
    Abbondanzo, SJ
    Anderson, PS
    Pollard, JW
    Lessey, BA
    Stewart, CL
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (07) : 3115 - 3120
  • [10] IL-1β induction of IL-6 and LIF in normal articular human chondrocytes involves the ERK, p38 and NFκB signaling pathways
    Fan, ZY
    Bau, B
    Yang, HQ
    Aigner, T
    [J]. CYTOKINE, 2004, 28 (01) : 17 - 24