miR-23b-3p regulates human endometrial epithelial cell adhesion implying a role in implantation

in Reproduction
Authors:
Siena BartonDepartment of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia
Gynaecology Research Centre, Royal Women's Hospital, Parkville, Victoria, Australia

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Wei ZhouDepartment of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia
Gynaecology Research Centre, Royal Women's Hospital, Parkville, Victoria, Australia

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https://orcid.org/0000-0001-9636-7963
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Leilani L SantosDepartment of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia
Gynaecology Research Centre, Royal Women's Hospital, Parkville, Victoria, Australia

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Ellen MenkhorstDepartment of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia
Gynaecology Research Centre, Royal Women's Hospital, Parkville, Victoria, Australia

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Guannan YangDepartment of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia
Gynaecology Research Centre, Royal Women's Hospital, Parkville, Victoria, Australia

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Wan Tinn TehDepartment of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia
The Royal Women’s Hospital, Parkville, VIC, Australia
Melbourne IVF, Melbourne, VIC, Australia
Epworth HealthCare, Melbourne, VIC, Australia

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Catarina AngDepartment of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia
The Royal Women’s Hospital, Parkville, VIC, Australia

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Tarana LuckyThe Royal Women’s Hospital, Parkville, VIC, Australia
Faculty of Medicine Dentistry&Health Sciences, University of Melbourne, Parkville, Victoria, Australia

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Evdokia DimitriadisDepartment of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia
Gynaecology Research Centre, Royal Women's Hospital, Parkville, Victoria, Australia

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Correspondence should be addressed to E dimitriadis; Email: evdokia.dimitriadis@unimelb.edu.au

*(S Barton and W Zhou contributed equally to this work)

DOI:
https://doi.org/10.1530/REP-22-0338
Volume/Issue:
Volume 165: Issue 4
Page Range:
407–416
Article Type:
Research Article
Online Publication Date:
08 Mar 2023
Copyright:
© Society for Reproduction and Fertility 2023
Restricted access

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In brief

miR-23b-3p expression is increased in fertile endometrium during receptivity. This study investigates the function of miR-23b-3p on endometrial adhesion and its downstream targets.

Abstract

The human endometrium undergoes dramatic remodeling throughout the menstrual cycle that is essential for successful blastocyst attachment and implantation in the mid-secretory (receptive) phase. microRNA (miR) plays a role in the preparation of endometrial receptivity. miR-23b-3p expression is increased in fertile endometrium during receptivity. Here, we aimed to investigate miR-23b-3p function during receptivity. qPCR and in situ hybridization were used to investigate the expression and localization of miR-23b-3p in human endometrium, respectively. Ishikawa cells (endometrial epithelial cell line) and endometrial organoid-derived epithelial cells were transfected with miR-23b-3p mimic, and trophoblast progenitor spheroid (blastocyst surrogate) adhesion assay was used to determine effects on blastocyst adhesion to endometrial cells. We demonstrated that miR-23b-3p was significantly upregulated in the fertile endometrium of the receptive phase compared to the non-receptive, proliferative phase. No difference was identified for the expression of miR-23b-3p between fertile and infertile mid-secretory phase endometrium. miR-23b-3p localized to the epithelium and stroma in the mid-secretory phase but was undetectable in the proliferative phase of fertile endometrium. Functionally, miR-23-3p overexpression in Ishikawa cells and fertile endometrial organoid-derived epithelial cells significantly improved their adhesive capacity to trophoblast progenitor spheroids. miR-23b-3p overexpression in infertile endometrial organoid-derived epithelial cells did not improve adhesion. Among 10 miR-predicted gene targets examined, miR-23b-3p overexpression in Ishikawa cells significantly reduced the expression of MET, secreted frizzled-related protein 4 (SFRP4) and acyl-CoA dehydrogenase short/branched chain (ACADSB) compared to control. The reduction of SFRP4 after miR23b-3p overexpression was confirmed by immunoblotting in fertile organoid-derived epithelial cells. SFRP4 expression in fertile endometrium exhibited an inverse expression pattern compared to miR-23b-3p and was higher in the proliferative phase compared to the mid-secretory phase. Overall, miR-23b-3p is likely a critical regulator of endometrial epithelial adhesion and receptivity.

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Sept 2018 onwards Past Year Past 30 Days
Full Text Views 85 85 15
PDF Downloads 138 138 23

 

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Print ISSN:
1470-1626
Online ISSN:
1741-7899

  • Aplin JD 2000 The cell biological basis of human implantation. Bailliere’s Best Practice and Research. Clinical Obstetrics and Gynaecology 14 757–764. (https://doi.org/10.1053/beog.2000.0116)

    • Search Google Scholar
    • Export Citation

  • Azhari F, Pence S, Hosseini MK, Balci BK, Cevik N, Bastu E & Gunel T 2022 The role of the serum exosomal and endometrial microRNAs in recurrent implantation failure. Journal of Maternal-Fetal and Neonatal Medicine 35 815–825. (https://doi.org/10.1080/14767058.2020.1849095)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Boretto M, Maenhoudt N, Luo X, Hennes A, Boeckx B, Bui B, Heremans R, Perneel L, Kobayashi H & Van Zundert I et al.2019 Patient-derived organoids from endometrial disease capture clinical heterogeneity and are amenable to drug screening. Nature Cell Biology 21 1041–1051. (https://doi.org/10.1038/s41556-019-0360-z)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Campos-Viguri GE, Peralta-Zaragoza O, Jiménez-Wences H, Longinos-González AE, Castañón-Sánchez CA, Ramírez-Carrillo M, Camarillo CL, Castañeda-Saucedo E, Jiménez-López MA & & Martínez-Carrillo DN 2020 MiR-23b-3p reduces the proliferation, migration and invasion of cervical cancer cell lines via the reduction of c-Met expression. Scientific Reports 10 1–14. (https://doi.org/10.1038/s41598-020-60143-x)

    • Search Google Scholar
    • Export Citation

  • Carmon KS & Loose DS 2008 Secreted frizzled-related protein 4 regulates two Wnt7a signaling pathways and inhibits proliferation in endometrial cancer cells. Molecular Cancer Research 6 1017–1028. (https://doi.org/10.1158/1541-7786.MCR-08-0039)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Castelbaum AJ, Ying L, Somkuti SG, Sun J, Ilesanmi AO & Lessey BA 1997 Characterization of integrin expression in a well differentiated endometrial adenocarcinoma cell line (Ishikawa). Journal of Clinical Endocrinology and Metabolism 82 136–142. (https://doi.org/10.1210/jcem.82.1.3658)

    • Search Google Scholar
    • Export Citation

  • Chen CH, Lu F, Yang WJ, Yang PE, Chen WM, Kang ST, Huang YS, Kao YC, Feng CT & Chang PC et al.2021 A novel platform for discovery of differentially expressed microRNAs in patients with repeated implantation failure. Fertility and Sterility 116 181–188. (https://doi.org/10.1016/j.fertnstert.2021.01.055)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chen D, Wu X, Xia M, Wu F, Ding J, Jiao Y, Zhan Q & An F 2017 Upregulated exosomic miR‑23b‑3p plays regulatory roles in the progression of pancreatic cancer. Oncology Reports 38 2182–2188. (https://doi.org/10.3892/or.2017.5919)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chen Q, Ni Y, Han M, Zhou WJ, Zhu XB & Zhang AJ 2020 Integrin-linked kinase improves uterine receptivity formation by activating Wnt/β-catenin signaling and up-regulating MMP-3/9 expression. American Journal of Translational Research 12 3011–3022.

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Craciunas L, Gallos I, Chu J, Bourne T, Quenby S, Brosens JJ & Coomarasamy A 2019 Conventional and modern markers of endometrial receptivity: a systematic review and meta-analysis. Human Reproduction Update 25 202–223. (https://doi.org/10.1093/humupd/dmy044)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Cuman C, Van Sinderen M, Gantier MP, Rainczuk K, Sorby K, Rombauts L, Osianlis T & Dimitriadis E 2015 Human blastocyst secreted microRNA regulate endometrial epithelial cell adhesion. EBio.EBiomedicine 2 1528–1535. (https://doi.org/10.1016/j.ebiom.2015.09.003)

    • Search Google Scholar
    • Export Citation

  • Díaz-Gimeno P, Horcajadas JA, Martínez-Conejero JA, Esteban FJ, Alamá P, Pellicer A & Simón C 2011 A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic signature. Fertility and Sterility 95 50–60. (https://doi.org/10.1016/j.fertnstert.2010.04.063)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Duncan WC, Shaw JL, Burgess S, McDonald SE, Critchley HO & Horne AW 2011 Ectopic pregnancy as a model to identify endometrial genes and signaling pathways important in decidualization and regulated by local trophoblast. PLOS ONE 6 e23595. (https://doi.org/10.1371/journal.pone.0023595)

    • Search Google Scholar
    • Export Citation

  • Evans J, Salamonsen LA, Winship A, Menkhorst E, Nie G, Gargett CE & Dimitriadis E 2016 Fertile ground: human endometrial programming and lessons in health and disease. Nature Reviews. Endocrinology 12 654–667. (https://doi.org/10.1038/nrendo.2016.116)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Evans J, Walker KJ, Bilandzic M, Kinnear S & Salamonsen LA 2020 A novel “embryo-endometrial” adhesion model can potentially predict “receptive” or “non-receptive” endometrium. Journal of Assisted Reproduction and Genetics 37 5–16. (https://doi.org/10.1007/s10815-019-01629-0)

    • Search Google Scholar
    • Export Citation

  • Fitzgerald HC, Evans J, Johnson N, Infusini G, Webb A, Rombauts LJR, Vollenhoven BJ, Salamonsen LA & Edgell TA 2018 Idiopathic infertility in women is associated with distinct changes in proliferative phase uterine fluid proteins. Biology of Reproduction 98 752–764. (https://doi.org/10.1093/biolre/ioy063)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Franasiak JM, Alecsandru D, Forman EJ, Gemmell LC, Goldberg JM, Llarena N, Margolis C, Laven J, Schoenmakers S & Seli E 2021 A review of the pathophysiology of recurrent implantation failure. Fertility and Sterility 116 1436–1448. (https://doi.org/10.1016/j.fertnstert.2021.09.014)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Garneau AS & Young SL 2021 Defining recurrent implantation failure: a profusion of confusion or simply an illusion? Fertility and Sterility 116 1432–1435. (https://doi.org/10.1016/j.fertnstert.2021.10.023)

    • Search Google Scholar
    • Export Citation

  • Gasiulė S, Dreize N, Kaupinis A, Ražanskas R, Čiupas L, Stankevičius V, Kapustina Ž, Laurinavičius A, Valius M & Vilkaitis G 2019 Molecular insights into miRNA-driven resistance to 5-fluorouracil and oxaliplatin chemotherapy: miR-23b modulates the epithelial–mesenchymal transition of colorectal cancer cells. Journal of Clinical Medicine 8 2115. (https://doi.org/10.3390/jcm8122115)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Gennarino VA, Sardiello M, Mutarelli M, Dharmalingam G, Maselli V, Lago G & Banfi S 2011 HOCTAR database: a unique resource for microRNA target prediction. Gene 480 51–58. (https://doi.org/10.1016/j.gene.2011.03.005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Governini L, Luongo FP, Haxhiu A, Piomboni P & Luddi A 2021 Main actors behind the endometrial receptivity and successful implantation. Tissue and Cell 73 101656. (https://doi.org/10.1016/j.tice.2021.101656)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Griffiths M, Van Sinderen M, Rainczuk K & Dimitriadis E 2019 miR-29c overexpression and COL4A1 downregulation in infertile human endometrium reduces endometrial epithelial cell adhesive capacity in vitro implying roles in receptivity. Scientific Reports 9 8644. (https://doi.org/10.1038/s41598-019-45155-6)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hammond SM 2015 An overview of microRNAs. Advanced Drug Delivery Reviews 87 3–14. (https://doi.org/10.1016/j.addr.2015.05.001)

  • Hibaoui Y & Feki A 2020 Organoid models of human endometrial development and disease. Frontiers in Cell and Developmental Biology 8 84. (https://doi.org/10.3389/fcell.2020.00084)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hu X, Wang Y, Liang H, Fan Q, Zhu R, Cui J, Zhang W, Zen K, Zhang CY & Hou D et al.2017 miR-23a/b promote tumor growth and suppress apoptosis by targeting PDCD4 in gastric cancer. Cell Death and Disease 8 e3059. (https://doi.org/10.1038/cddis.2017.447)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lee DK, Grantham RN, Trachte AL, Mannion JD & Wilson CL 2006 Activation of the canonical Wnt/β-catenin pathway enhances monocyte adhesion to endothelial cells. Biochemical and Biophysical Research Communications 347 109–116. (https://doi.org/10.1016/j.bbrc.2006.06.082)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Li LN, Zhang HD, Yuan SJ, Tian ZY, Wang L & Sun ZX 2007 Artesunate attenuates the growth of human colorectal carcinoma and inhibits hyperactive Wnt/β‐catenin pathway. International Journal of Cancer 121 1360–1365. (https://doi.org/10.1002/ijc.22804)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Liang J, Wang S & Wang Z 2017 Role of microRNAs in embryo implantation. Reproductive Biology and Endocrinology : RB&E 15 90. (https://doi.org/10.1186/s12958-017-0309-7)

    • Search Google Scholar
    • Export Citation

  • Liu Y, Kodithuwakku SP, Ng PY, Chai J, Ng EH, Yeung WS, Ho PC & Lee KF 2010 Excessive ovarian stimulation up-regulates the Wnt-signaling molecule DKK1 in human endometrium and may affect implantation: an in vitro co-culture study. Human Reproduction 25 479–490. (https://doi.org/10.1093/humrep/dep429)

    • Search Google Scholar
    • Export Citation

  • Mohamed OA, Jonnaert M, Labelle-Dumais C, Kuroda K, Clarke HJ & Dufort D 2005 Uterine Wnt/β-catenin signaling is required for implantation. Proceedings of the National Academy of Sciences of the United States of America 102 8579–8584. (https://doi.org/10.1073/pnas.0500612102)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Murphy CR 2004 Uterine receptivity and the plasma membrane transformation. Cell Research 14 259–267. (https://doi.org/10.1038/sj.cr.7290227)

  • Naidu S, Shi L, Magee P, Middleton JD, Laganá A, Sahoo S, Leong HS, Galvin M, Frese K & & Dive C 2017 PDGFR-modulated miR-23b cluster and miR-125a-5p suppress lung tumorigenesis by targeting multiple components of KRAS and NF-kB pathways. Scientific Reports 7 1–14. (https://doi.org/10.1038/s41598-017-14843-6)

    • Search Google Scholar
    • Export Citation

  • Owusu-Akyaw A, Krishnamoorthy K, Goldsmith LT & Morelli SS 2019 The role of mesenchymal–epithelial transition in endometrial function. Human Reproduction Update 25 114–133. (https://doi.org/10.1093/humupd/dmy035)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pawar NM & Rao P 2018 Secreted frizzled related protein 4 (sFRP4) update: A brief review. Cellular Signalling 45 63–70. (https://doi.org/10.1016/j.cellsig.2018.01.019)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Pellegrino L, Stebbing J, Braga VM, Frampton AE, Jacob J, Buluwela L, Jiao LR, Periyasamy M, Madsen CD & Caley MP et al.2013 miR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts. Nucleic Acids Research 41 5400–5412. (https://doi.org/10.1093/nar/gkt245)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ran Y, He J, Chen R, Qin Y, Liu Z, Zhou Y, Yin N, Qi H & Zhou W 2022 Investigation and validation of molecular characteristics of endometrium in recurrent miscarriage and unexplained infertility from a transcriptomic perspective. International Journal of Medical Sciences 19 546–562. (https://doi.org/10.7150/ijms.69648)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Revel A, Achache H, Stevens J, Smith Y & Reich R 2011 MicroRNAs are associated with human embryo implantation defects. Human Reproduction 26 2830–2840. (https://doi.org/10.1093/humrep/der255)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Shekibi M, Heng S & Nie G 2022 MicroRNAs in the regulation of endometrial receptivity for embryo implantation. International Journal of Molecular Sciences 23 6210. (https://doi.org/10.3390/ijms23116210)

    • Search Google Scholar
    • Export Citation

  • Takamura M, Zhou W, Rombauts L & Dimitriadis E 2020 The long noncoding RNA PTENP1 regulates human endometrial epithelial adhesive capacity in vitro: implications in infertility. Biology of Reproduction 102 53–62. (https://doi.org/10.1093/biolre/ioz173)

    • Search Google Scholar
    • Export Citation

  • Turco MY, Gardner L, Hughes J, Cindrova-Davies T, Gomez MJ, Farrell L, Hollinshead M, Marsh SGE, Brosens JJ & Critchley HO et al.2017 Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium. Nature Cell Biology 19 568–577. (https://doi.org/10.1038/ncb3516)

    • Search Google Scholar
    • Export Citation

  • Whitby S, Zhou W & Dimitriadis E 2020 Alterations in epithelial cell polarity during endometrial receptivity: A systematic review. Frontiers in Endocrinology 11 596324. (https://doi.org/10.3389/fendo.2020.596324)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wilcox AJ, Weinberg CR, O'Connor JF, Baird DD, Schlatterer JP, Canfield RE, Armstrong EG & Nisula BC 1988 Incidence of early loss of pregnancy. New England Journal of Medicine 319 189–194. (https://doi.org/10.1056/NEJM198807283190401)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Wu B, Li Y, Nie N, Shen X, Jiang W, Liu Y, Gong L, An C, Zhao K & & Yao X 2022 SFRP4+ stromal cell subpopulation with IGF1 signaling in human endometrial regeneration. Cell Discovery 8 1–16. (https://doi.org/10.1038/s41421-022-00438-7)

    • Search Google Scholar
    • Export Citation

  • Zdravkovic T, Nazor KL, Larocque N, Gormley M, Donne M, Hunkapillar N, Giritharan G, Bernstein HS, Wei G & Hebrok M et al.2015 Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification. Development 142 4010–4025. (https://doi.org/10.1242/dev.122846)

    • Search Google Scholar
    • Export Citation

  • Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, De Mouzon J, Sokol R, Rienzi L, Sunde A, Schmidt L & Cooke ID et al.2017 The international glossary on infertility and fertility care, 2017. Human Reproduction 32 1786–1801. (https://doi.org/10.1093/humrep/dex234)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhang H, Hao Y, Yang J, Zhou Y, Li J, Yin S, Sun C, Ma M, Huang Y & Xi JJ 2011 Genome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis. Nature Communications 2 554. (https://doi.org/10.1038/ncomms1555)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhou W, Barton S, Cui J, Santos LL, Yang G, Stern C, Kieu V, Teh WT, Ang C & Lucky T et al.2022 Infertile human endometrial organoid apical protein secretions are dysregulated and impair trophoblast progenitor cell adhesion. Frontiers in Endocrinology 13 1067648. (https://doi.org/10.3389/fendo.2022.1067648)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhou W, Menkhorst E & Dimitriadis E 2021 Jagged1 regulates endometrial receptivity in both humans and mice. FASEB Journal 35 e21784. (https://doi.org/10.1096/fj.202100590R)

    • PubMed
    • Search Google Scholar
    • Export Citation