Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
권호 표지
DOI QR코드

DOI QR Code

Endometrial profilin 1: A key player in embryo-endometrial crosstalk

  • Lee, Chang-Jin (Department of Biomedical Science, School of Life Science, CHA University) ;
  • Hong, Seon-Hwa (CHA Fertility Center Bundang, School of Medicine, CHA University) ;
  • Yoon, Min-Ji (Department of Biomedical Science, School of Life Science, CHA University) ;
  • Lee, Kyung-Ah (Department of Biomedical Science, School of Life Science, CHA University) ;
  • Ko, Jung-Jae (Department of Biomedical Science, School of Life Science, CHA University) ;
  • Koo, Hwa Seon (CHA Fertility Center Bundang, School of Medicine, CHA University) ;
  • Kim, Jee Hyun (CHA Fertility Center Bundang, School of Medicine, CHA University) ;
  • Choi, Dong Hee (CHA Fertility Center Bundang, School of Medicine, CHA University) ;
  • Kwon, Hwang (CHA Fertility Center Bundang, School of Medicine, CHA University) ;
  • Kang, Youn-Jung (Department of Biomedical Science, School of Life Science, CHA University)
  • Received : 2019.12.05
  • Accepted : 2019.12.14
  • Published : 2020.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objective: Despite extensive research on implantation failure, little is known about the molecular mechanisms underlying the crosstalk between the embryo and the maternal endometrium, which is critical for successful pregnancy. Profilin 1 (PFN1), which is expressed both in the embryo and in the endometrial epithelium, acts as a potent regulator of actin polymerization and the cytoskeletal network. In this study, we identified the specific role of endometrial PFN1 during embryo implantation. Methods: Morphological alterations depending on the status of PFN1 expression were assessed in PFN1-depleted or control cells grown on Matrigel-coated cover glass. Day-5 mouse embryos were cocultured with Ishikawa cells. Comparisons of the rates of F-actin formation and embryo attachment were performed by measuring the stability of the attached embryo onto PFN1-depleted or control cells. Results: Depletion of PFN1 in endometrial epithelial cells induced a significant reduction in cell-cell adhesion displaying less formation of colonies and a more circular cell shape. Mouse embryos co-cultured with PFN1-depleted cells failed to form actin cytoskeletal networks, whereas more F-actin formation in the direction of surrounding PFN1-intact endometrial epithelial cells was detected. Furthermore, significantly lower embryo attachment stability was observed in PFN1-depleted cells than in control cells. This may have been due to reduced endometrial receptivity caused by impaired actin cytoskeletal networks associated with PFN1 deficiency. Conclusion: These observations definitively demonstrate an important role of PFN1 in mediating cell-cell adhesion during the initial stage of embryo implantation and suggest a potential therapeutic target or novel biomarker for patients suffering from implantation failure.

Keywords

References

  1. Bashiri A, Halper KI, Orvieto R. Recurrent Implantation Failureupdate overview on etiology, diagnosis, treatment and future directions. Reprod Biol Endocrinol 2018;16:121. https://doi.org/10.1186/s12958-018-0414-2
  2. Simon A, Laufer N. Assessment and treatment of repeated implantation failure (RIF). J Assist Reprod Genet 2012;29:1227-39. https://doi.org/10.1007/s10815-012-9861-4
  3. Dey SK, Lim H, Das SK, Reese J, Paria BC, Daikoku T, et al. Molecular cues to implantation. Endocr Rev 2004;25:341-73. https://doi.org/10.1210/er.2003-0020
  4. Psychoyos A. Hormonal control of ovoimplantation. Vitam Horm 1973;31:201-56. https://doi.org/10.1016/S0083-6729(08)60999-1
  5. Tabibzadeh S. Molecular control of the implantation window. Hum Reprod Update 1998;4:465-71. https://doi.org/10.1093/humupd/4.5.465
  6. Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update 2006;12:731-46. https://doi.org/10.1093/humupd/dml004
  7. Norwitz ER. Defective implantation and placentation: laying the blueprint for pregnancy complications. Reprod Biomed Online 2006;13:591-9. https://doi.org/10.1016/S1472-6483(10)60649-9
  8. Margalioth EJ, Ben-Chetrit A, Gal M, Eldar-Geva T. Investigation and treatment of repeated implantation failure following IVF-ET. Hum Reprod 2006;21:3036-43. https://doi.org/10.1093/humrep/del305
  9. Koot YE, Boomsma CM, Eijkemans MJ, Lentjes EG, Macklon NS. Recurrent pre-clinical pregnancy loss is unlikely to be a 'cause' of unexplained infertility. Hum Reprod 2011;26:2636-41. https://doi.org/10.1093/humrep/der217
  10. Tang DD, Gerlach BD. The roles and regulation of the actin cytoskeleton, intermediate filaments and microtubules in smooth muscle cell migration. Respir Res 2017;18:54. https://doi.org/10.1186/s12931-017-0544-7
  11. Bazer FW, Wu G, Spencer TE, Johnson GA, Burghardt RC, Bayless K. Novel pathways for implantation and establishment and maintenance of pregnancy in mammals. Mol Hum Reprod 2010;16:135-52. https://doi.org/10.1093/molehr/gap095
  12. Tan K, An L, Wang SM, Wang XD, Zhang ZN, Miao K, et al. Actin disorganization plays a vital role in impaired embryonic development of in vitro-produced mouse preimplantation embryos. PLoS One 2015;10:e0130382. https://doi.org/10.1371/journal.pone.0130382
  13. Alkam D, Feldman EZ, Singh A, Kiaei M. Profilin1 biology and its mutation, actin(g) in disease. Cell Mol Life Sci 2017;74:967-81. https://doi.org/10.1007/s00018-016-2372-1
  14. Berglund L, Bjorling E, Oksvold P, Fagerberg L, Asplund A, Szigyarto CA, et al. A genecentric human protein atlas for expression profiles based on antibodies. Mol Cell Proteomics 2008;7:2019-27. https://doi.org/10.1074/mcp.R800013-MCP200
  15. Thul PJ, Akesson L, Wiking M, Mahdessian D, Geladaki A, Ait Blal H, et al. A subcellular map of the human proteome. Science 2017;356:eaal3321. https://doi.org/10.1126/science.aal3321
  16. Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A, et al. Proteomics: tissue-based map of the human proteome. Science 2015;347:1260419. https://doi.org/10.1126/science.1260419
  17. Bae YH, Ding Z, Zou L, Wells A, Gertler F, Roy P. Loss of profilin-1 expression enhances breast cancer cell motility by Ena/VASP proteins. J Cell Physiol 2009;219:354-64. https://doi.org/10.1002/jcp.21677
  18. Zou L, Ding Z, Roy P. Profilin-1 overexpression inhibits proliferation of MDA-MB-231 breast cancer cells partly through p27kip1 upregulation. J Cell Physiol 2010;223:623-9. https://doi.org/10.1002/jcp.22058
  19. Kang YJ, Forbes K, Carver J, Aplin JD. The role of the osteopontinintegrin ${\alpha}v{\beta}3$ interaction at implantation: functional analysis using three different in vitro models. Hum Reprod 2014;29:739-49. https://doi.org/10.1093/humrep/det433
  20. Kang YJ, Lees M, Matthews LC, Kimber SJ, Forbes K, Aplin JD. MiR-145 suppresses embryo-epithelial juxtacrine communication at implantation by modulating maternal IGF1R. J Cell Sci 2015;128:804-14. https://doi.org/10.1242/jcs.164004
  21. Carver J, Martin K, Spyropoulou I, Barlow D, Sargent I, Mardon H. An in-vitro model for stromal invasion during implantation of the human blastocyst. Hum Reprod 2003;18:283-90. https://doi.org/10.1093/humrep/deg072
  22. Kang YJ, Balter B, Csizmadia E, Haas B, Sharma H, Bronson R, et al. Contribution of classical end-joining to PTEN inactivation in p53-mediated glioblastoma formation and drug-resistant survival. Nat Commun 2017;8:14013. https://doi.org/10.1038/ncomms14013
  23. Ding Z, Roy P. Profilin-1 versus profilin-2: two faces of the same coin? Breast Cancer Res 2013;15:311. https://doi.org/10.1186/bcr3433
  24. Cheng YJ, Zhu ZX, Zhou JS, Hu ZQ, Zhang JP, Cai QP, et al. Silencing profilin-1 inhibits gastric cancer progression via integrin ${\beta}1$/focal adhesion kinase pathway modulation. World J Gastroenterol 2015;21:2323-35. https://doi.org/10.3748/wjg.v21.i8.2323
  25. Suetsugu S, Takenawa T. Regulation of cortical actin networks in cell migration. Int Rev Cytol 2003;229:245-86. https://doi.org/10.1016/S0074-7696(03)29006-9
  26. Bachir AI, Horwitz AR, Nelson WJ, Bianchini JM. Actin-based adhesion modules mediate cell interactions with the extracellular matrix and neighboring cells. Cold Spring Harb Perspect Biol 2017;9:a023234. https://doi.org/10.1101/cshperspect.a023234
  27. Aplin JD, Ruane PT. Embryo-epithelium interactions during implantation at a glance. J Cell Sci 2017;130:15-22. https://doi.org/10.1242/jcs.175943
  28. Nimbkar-Joshi S, Rosario G, Katkam RR, Manjramkar DD, Metkari SM, Puri CP, et al. Embryo-induced alterations in the molecular phenotype of primate endometrium. J Reprod Immunol 2009;83:65-71. https://doi.org/10.1016/j.jri.2009.08.011
  29. Singh H, Aplin JD. Adhesion molecules in endometrial epithelium: tissue integrity and embryo implantation. J Anat 2009;215:3-13. https://doi.org/10.1111/j.1469-7580.2008.01034.x
  30. Kim SM, Kim JS. A review of mechanisms of implantation. Dev Reprod 2017;21:351-9. https://doi.org/10.12717/DR.2017.21.4.351
  31. Ding Z, Lambrechts A, Parepally M, Roy P. Silencing profilin-1 inhibits endothelial cell proliferation, migration and cord morphogenesis. J Cell Sci 2006;119(Pt 19):4127-37. https://doi.org/10.1242/jcs.03178
  32. Zou L, Hazan R, Roy P. Profilin-1 overexpression restores adherens junctions in MDA-MB-231 breast cancer cells in R-cadherindependent manner. Cell Motil Cytoskeleton 2009;66:1048-56. https://doi.org/10.1002/cm.20407
  33. Bitko V, Oldenburg A, Garmon NE, Barik S. Profilin is required for viral morphogenesis, syncytium formation, and cell-specific stress fiber induction by respiratory syncytial virus. BMC Microbiol 2003;3:9. https://doi.org/10.1186/1471-2180-3-9
  34. Quinlan MP. Vinculin, VASP, and profilin are coordinately regulated during actin remodeling in epithelial cells, which requires de novo protein synthesis and protein kinase signal transduction pathways. J Cell Physiol 2004;200:277-90. https://doi.org/10.1002/jcp.20009
  35. Rawe VY, Payne C, Schatten G. Profilin and actin-related proteins regulate microfilament dynamics during early mammalian embryogenesis. Hum Reprod 2006;21:1143-53. https://doi.org/10.1093/humrep/dei480
  36. Caglayan E, Romeo GR, Kappert K, Odenthal M, Sudkamp M, Body SC, et al. Profilin-1 is expressed in human atherosclerotic plaques and induces atherogenic effects on vascular smooth muscle cells. PLoS One 2010;5:e13608. https://doi.org/10.1371/journal.pone.0013608
  37. Thery C, Boussac M, Veron P, Ricciardi-Castagnoli P, Raposo G, Garin J, et al. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol 2001;166:7309-18. https://doi.org/10.4049/jimmunol.166.12.7309
  38. Menkhorst EM, Van Sinderen ML, Rainczuk K, Cuman C, Winship A, Dimitriadis E. Invasive trophoblast promote stromal fibroblast decidualization via Profilin 1 and ALOX5. Sci Rep 2017;7:8690. https://doi.org/10.1038/s41598-017-05947-0
  39. Liang X, Jin Y, Wang H, Meng X, Tan Z, Huang T, et al. Transgelin 2 is required for embryo implantation by promoting actin polymerization. FASEB J 2019;33:5667-75. https://doi.org/10.1096/fj.201802158rrr

Cited by

  1. Sperm Proteome after Interaction with Reproductive Fluids in Porcine: From the Ejaculation to the Fertilization Site vol.21, pp.17, 2020, https://doi.org/10.3390/ijms21176060