WNT16 from decidual stromal cells regulates HTR8/SVneo trophoblastic cell function via AKT/beta-catenin pathway

in Reproduction
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Xinyi Li NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China

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Jiaxin Shi NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China

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Weijie Zhao NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China

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Xixi Huang NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China

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Liyuan Cui NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China
Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacy, Fudan University, Shanghai, China

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Lu Liu NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China
Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacy, Fudan University, Shanghai, China

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Xueling Jin NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China

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Djin Li NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China

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Xuan Zhang NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China

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Meirong Du NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China
State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau SAR, China

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https://orcid.org/0000-0002-5307-6784

Correspondence should be addressed to X Zhang or M Du; Email: zhangxuancw@outlook.com or dmrlq1973@sina.cn

*(X Li and J Shi contributed equally to this work)

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Decidual stromal cells (DSCs) modulate the function of trophoblasts through various factors. Wnt signaling pathway is active at the maternal–fetal interface. Here, we isolated endometrial stromal cells (ESCs) from women of reproductive ages and DSCs from normal pregnancy during the first trimester (6–10 weeks). Real-time quantitative PCR and western blotting were used to screen out the most variable WNT ligands between ESCs and DSCs, which turned out to be WNT16. Both culture mediums from DSCs and recombinant protein of human WNT16 enhanced the survival and invasion of HTR8/SVneo trophoblastic cells. Furthermore, the regulation of DSCs on trophoblast was partly blockaded after we knocked down WNT16 in DSCs. Treating HTR8/SVneo trophoblastic cells with small molecular inhibitors and small interfering RNA (siRNA), we found that the activity of AKT/beta-catenin (CTNNB1) correlated with the effect of WNT16. The crosstalk of WNT16/AKT/beta-catenin between DSCs and trophoblasts was determined to be downregulated in unexplained recurrent spontaneous abortion. This study suggests that WNT16 from DSCs promotes HTR8/SVneo trophoblastic cells invasion and survival via AKT/beta-catenin pathway at the maternal–fetal interface in human early pregnancy. The disturbance of this crosstalk between DSCs and trophoblasts might cause pregnancy failure.

 

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  • Bischof P & Campana A 2000 A putative role for oncogenes in trophoblast invasion? Human Reproduction 15 (Supplement 6) 5158.

  • Diacou R, Zhao Y, Zheng D, Cvekl A & Liu W 2018 Six3 and Six6 are jointly required for the maintenance of multipotent retinal progenitors through both positive and negative regulation. Cell Reports 25 2510 .e42523.e4. (https://doi.org/10.1016/j.celrep.2018.10.106)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Du MR, Zhou WH, Piao HL, Li MQ, Tang CL & Li DJ 2012 Cyclosporin A promotes crosstalk between human cytotrophoblast and decidual stromal cell through up-regulating CXCL12/CXCR4 interaction. Human Reproduction 27 19551965. (https://doi.org/10.1093/humrep/des111)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Du MR, Guo PF, Piao HL, Wang SC, Sun C, Jin LP, Tao Y, Li YH, Zhang D & Zhu R et al.2014 Embryonic trophoblasts induce decidual regulatory T cell differentiation and maternal-fetal tolerance through thymic stromal lymphopoietin instructing dendritic cells. Journal of Immunology 192 15021511. (https://doi.org/10.4049/jimmunol.1203425)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fan M, Xu Y, Hong F, Gao X, Xin G, Hong H, Dong L & Zhao X 2016 Rac1/beta-catenin signalling pathway contributes to trophoblast cell invasion by targeting snail and MMP9. Cellular Physiology and Biochemistry 38 13191332. (https://doi.org/10.1159/000443076)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fan DX, Zhou WJ, Jin LP, Li MQ, Xu XH & Xu CJ 2019 Trophoblast-derived CXCL16 decreased granzyme B production of decidual gammadelta T cells and promoted Bcl-xL expression of trophoblasts. Reproductive Sciences 26 532542. (https://doi.org/10.1177/1933719118777638)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Farah O, Biechele S, Rossant J & Dufort D 2017 Porcupine-dependent Wnt activity within the uterine epithelium is essential for fertility. Biology of Reproduction 97 688697. (https://doi.org/10.1093/biolre/iox119)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Farin HF, Jordens I, Mosa MH, Basak O, Korving J, Tauriello DV, de Punder K, Angers S, Peters PJ & Maurice MM et al.2016 Visualization of a short-range Wnt gradient in the intestinal stem-cell niche. Nature 530 340343. (https://doi.org/10.1038/nature16937)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Foulquier S, Daskalopoulos EP, Lluri G, Hermans KCM, Deb A & Blankesteijn WM 2018 WNT signaling in cardiac and vascular disease. Pharmacological Reviews 70 68141. (https://doi.org/10.1124/pr.117.013896)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fujita N & Tsuruo T 1998 Involvement of Bcl-2 cleavage in the acceleration of vp-16-induced U937 cell apoptosis. Biochemical and Biophysical Research Communications 246 484488. (https://doi.org/10.1006/bbrc.1998.8587)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Grisaru-Granovsky S, Maoz M, Barzilay O, Yin YJ, Prus D & Bar-Shavit R 2009 Protease activated receptor-1, PAR1, promotes placenta trophoblast invasion and beta-catenin stabilization. Journal of Cellular Physiology 218 512521. (https://doi.org/10.1002/jcp.21625)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Guo W, Zhu X, Yan L & Qiao J 2018 The present and future of whole-exome sequencing in studying and treating human reproductive disorders. Journal of Genetics and Genomics 45 517525. (https://doi.org/10.1016/j.jgg.2018.08.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Han Y, You X, Xing W, Zhang Z & Zou W 2018 Paracrine and endocrine actions of bone-the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts. Bone Research 6 16. (https://doi.org/10.1038/s41413-018-0019-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Huang SM, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, Charlat O, Wiellette E, Zhang Y & Wiessner S et al.2009 Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 461 614620. (https://doi.org/10.1038/nature08356)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jiang F, Parsons CJ & Stefanovic B 2006 Gene expression profile of quiescent and activated rat hepatic stellate cells implicates Wnt signaling pathway in activation. Journal of Hepatology 45 401409. (https://doi.org/10.1016/j.jhep.2006.03.016)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jovanovic M & Vicovac L 2009 Interleukin-6 stimulates cell migration, invasion and integrin expression in HTR-8/SVneo cell line. Placenta 30 320328. (https://doi.org/10.1016/j.placenta.2009.01.013)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Koundouros N, Karali E, Tripp A, Valle A, Inglese P, Perry NJS, Magee DJ, Anjomani Virmouni S, Elder GA & Tyson AL et al.2020 Metabolic fingerprinting links oncogenic PIK3CA with enhanced arachidonic acid-derived eicosanoids. Cell 181 1596 .e271611.e27. (https://doi.org/10.1016/j.cell.2020.05.053)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lavini-Ramos C, Silva HM, Soares-Schanoski A, Monteiro SM, Ferreira LRP, Pacanaro AP, Gomes S, Batista J, Fae K & Kalil J et al.2017 MMP9 integrates multiple immunoregulatory pathways that discriminate high suppressive activity of human mesenchymal stem cells. Scientific Reports 7 874. (https://doi.org/10.1038/s41598-017-00923-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Li TC, Makris M, Tomsu M, Tuckerman E & Laird S 2002 Recurrent miscarriage: aetiology, management and prognosis. Human Reproduction Update 8 463481. (https://doi.org/10.1093/humupd/8.5.463)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Li N, Li S, Wang Y, Wang J, Wang K, Liu X, Li Y & Liu J 2017 Decreased expression of WNT2 in villi of unexplained recurrent spontaneous abortion patients may cause trophoblast cell dysfunction via downregulated Wnt/beta-catenin signaling pathway. Cell Biology International 41 898907. (https://doi.org/10.1002/cbin.10807)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lie DC, Colamarino SA, Song HJ, Desire L, Mira H, Consiglio A, Lein ES, Jessberger S, Lansford H & Dearie AR et al.2005 Wnt signalling regulates adult hippocampal neurogenesis. Nature 437 13701375. (https://doi.org/10.1038/nature04108)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lunghi L, Ferretti ME, Medici S, Biondi C & Vesce F 2007 Control of human trophoblast function. Reproductive Biology and Endocrinology 5 6. (https://doi.org/10.1186/1477-7827-5-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mazzoni J, Smith JR, Shahriar S, Cutforth T, Ceja B & Agalliu D 2017 The Wnt inhibitor Apcdd1 coordinates vascular remodeling and barrier maturation of retinal blood vessels. Neuron 96 1055 .e61069.e6. (https://doi.org/10.1016/j.neuron.2017.10.025)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Moverare-Skrtic S, Henning P, Liu X, Nagano K, Saito H, Borjesson AE, Sjogren K, Windahl SH, Farman H & Kindlund B et al.2014 Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures. Nature Medicine 20 12791288. (https://doi.org/10.1038/nm.3654)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nayeem SB, Arfuso F, Dharmarajan A & Keelan JA 2016 Role of Wnt signalling in early pregnancy. Reproduction, Fertility, and Development 28 525544. (https://doi.org/10.1071/RD14079)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ono M, Yin P, Navarro A, Moravek MB, Coon JSt, Druschitz SA, Serna VA, Qiang W, Brooks DC & Malpani SS et al.2013 Paracrine activation of WNT/beta-catenin pathway in uterine leiomyoma stem cells promotes tumor growth. PNAS 110 1705317058. (https://doi.org/10.1073/pnas.1313650110)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pijnenborg R, Vercruysse L & Hanssens M 2006 The uterine spiral arteries in human pregnancy: facts and controversies. Placenta 27 939958. (https://doi.org/10.1016/j.placenta.2005.12.006)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schatz F, Guzeloglu-Kayisli O, Arlier S, Kayisli UA & Lockwood CJ 2016 The role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding. Human Reproduction Update 22 497515. (https://doi.org/10.1093/humupd/dmw004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sharma S, Godbole G & Modi D 2016 Decidual control of trophoblast invasion. American Journal of Reproductive Immunology 75 341350. (https://doi.org/10.1111/aji.12466)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sonderegger S, Pollheimer J & Knofler M 2010 Wnt signalling in implantation, decidualisation and placental differentiation – review. Placenta 31 839847. (https://doi.org/10.1016/j.placenta.2010.07.011)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Suman P & Gupta SK 2014 STAT3 and ERK1/2 cross-talk in leukaemia inhibitory factor mediated trophoblastic JEG-3 cell invasion and expression of mucin 1 and Fos. American Journal of Reproductive Immunology 72 6574. (https://doi.org/10.1111/aji.12248)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wang Z, Chen Z, Yang J, Yang Z, Yin J, Duan X, Shen H, Li H, Wang Z & Chen G 2019 Treatment of secondary brain injury by perturbing postsynaptic density protein-95-NMDA receptor interaction after intracerebral hemorrhage in rats. Journal of Cerebral Blood Flow and Metabolism 39 15881601. (https://doi.org/10.1177/0271678X18762637)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wu ZM, Yang H, Li M, Yeh CC, Schatz F, Lockwood CJ, Di W & Huang SJ 2012 Pro-inflammatory cytokine-stimulated first trimester decidual cells enhance macrophage-induced apoptosis of extravillous trophoblasts. Placenta 33 188194. (https://doi.org/10.1016/j.placenta.2011.12.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wu HX, Jin LP, Xu B, Liang SS & Li DJ 2014 Decidual stromal cells recruit Th17 cells into decidua to promote proliferation and invasion of human trophoblast cells by secreting IL-17. Cellular and Molecular Immunology 11 253262. (https://doi.org/10.1038/cmi.2013.67)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zenke S, Palm MM, Braun J, Gavrilov A, Meiser P, Bottcher JP, Beyersdorf N, Ehl S, Gerard A & Lammermann T et al.2020 Quorum regulation via nested antagonistic feedback circuits mediated by the receptors CD28 and CTLA-4 confers robustness to T cell population dynamics. Immunity 52 313 .e7327.e7. (https://doi.org/10.1016/j.immuni.2020.01.018)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhang H, Hou L, Li CM & Zhang WY 2013 The chemokine CXCL6 restricts human trophoblast cell migration and invasion by suppressing MMP-2 activity in the first trimester. Human Reproduction 28 23502362. (https://doi.org/10.1093/humrep/det258)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhang S, Kim B, Zhu X, Gui X, Wang Y, Lan Z, Prabhu P, Fond K, Wang A & Guo F 2020 Glial type specific regulation of CNS angiogenesis by HIFalpha-activated different signaling pathways. Nature Communications 11 2027. (https://doi.org/10.1038/s41467-020-15656-4)

    • PubMed
    • Search Google Scholar
    • Export Citation