Development and Reproduction (한국발생생물학회지:발생과생식)

The Korean Society of Developmental Biology (한국발생생물학회)
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A Review of Mechanisms of Implantation

  • Kim, Su-Mi (Dept. of Obstetrics and Gynecology, College of Medicine, Dankook University) ;
  • Kim, Jong-Soo (Dept. of Obstetrics and Gynecology, College of Medicine, Dankook University)
  • Received : 2017.11.20
  • Accepted : 2017.12.08
  • Published : 2017.12.31
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Abstract

Implantation is a highly organized process that involves an interaction between a receptive uterus and a competent blastocyst. In humans, natural fecundity suggests that the chance of conception per cycle is relatively low (~30%) and two-third of lost pregnancies occur because of implantation failure. Defective implantation leads to adverse pregnancy outcomes including infertility, spontaneous miscarriage, intrauterine fetal growth restriction and preeclampsia. With use of advanced scientific technologies, gene expression analysis and genetically-engineered animal models have revealed critical cellular networks and molecular pathways. But, because of ethical restrictions and the lack of a mechanistic experiment, comprehensive steps in human implantation have still not been completely understood. This review primarily focuses on the recent advances in mechanisms of implantation. Because infertility is an emerging issue these days, gaining an understanding the molecular and hormonal signaling pathway will improve the outcome of natural pregnancy and assisted reproductive technology.

Keywords

References

  1. Bischof P, Campana A (1997) Trophoblast differentiation and invasion: its significance for human embryo implantation. Early Pregnancy 3:81-95.
  2. Burrows TD, King A, Loke Y (1996) Trophoblast migration during human placental implantation. Hum Reprod Update 2:307-321. https://doi.org/10.1093/humupd/2.4.307
  3. Cha J, Sun X, Dey SK (2012) Mechanisms of implantation: strategies for successful pregnancy. Nat Med 18:1754-1767. https://doi.org/10.1038/nm.3012
  4. Chillaron J, Roca R, Valencia A, Zorzano A, Palacin M (2001) Heteromeric amino acid transporters: biochemistry, genetics, and physiology. Am J Physiol Renal Physiol 281:995-1018.
  5. Cohen M, Meisser A, Bischof P (2006) Metalloproteinases and human placental invasiveness. Placenta 27:783-793. https://doi.org/10.1016/j.placenta.2005.08.006
  6. Das SK, Wang XN, Paria BC, Damm D, Abraham JA, Klagsbrun M, Andrews GK, Dey SK (1994) Heparin-binding EGF-like growth factor gene is induced in the mouse uterus temporally by the blastocyst solely at the site of its apposition: a possible ligand for interaction with blastocyst EGF-receptor in implantation. Development 120:1071-1083.
  7. Dominguez F, Gadea B, Mercader A, Esteban FJ, Pellicer A, Simon C (2010a) Embryologic outcome and secretome profile of implanted blastocysts obtained after coculture in human endometrial epithelial cells versus the sequential system. Fertil Steril 93:774-782. https://doi.org/10.1016/j.fertnstert.2008.10.019
  8. Dominguez F, Meseguer M, Aparicio-Ruiz B, Piqueras P, Quinonero A, Simon C (2015b) New strategy for diagnosing embryo implantation potential by combining proteomics and time-lapse technologies. Fertil Steril 104:908-914. https://doi.org/10.1016/j.fertnstert.2015.06.032
  9. Dominguez F, Simon C, Quinonero A, Ramirez MA, Gonzalez-Munoz E, Burghardt H, Cervero A, Martinez S, Pellicer A, Palacin M, Sanchez-Madrid F, Yanez-Mo M (2010c) Human endometrial CD98 is essential for blastocyst adhesion. PLoS One 5:e13380. https://doi.org/10.1371/journal.pone.0013380
  10. Emonard H, Christiane Y, Smet M, Grimaud J, Foidart JM (1990) Type IV and interstitial collagenolytic activities in normal and malignant trophoblast cells are specifically regulated by the extracellular matrix. Invasion Metastasis 10:170-177.
  11. Fukuda MN, Sugihara K (2007) Signal transduction in human embryo implantation. Cell Cycle 6:1153-1156. https://doi.org/10.4161/cc.6.10.4266
  12. Genbacev OD, Prakobphol A, Foulk RA, Krtolica AR, Ilic D, Singer MS, Yang ZQ, Kiessling LL, Rosen SD, Fisher SJ (2003) Trophoblast L-selectin-mediated adhesion at the maternal-fetal interface. Science 299:405-408. https://doi.org/10.1126/science.1079546
  13. Ghosh D, De P, Sengupta J (1994) Luteal phase ovarian oestrogen is not essential for implantation and maintenance of pregnancy from surrogate embryo transfer in the rhesus monkey. Hum Reprod 9:629-637. https://doi.org/10.1093/oxfordjournals.humrep.a138561
  14. Gipson IK, Blalock T, Tisdale A, Spurr-Michaud S, Allcorn S, Stavreus-Evers A, Gemzell K (2008) MUC16 is lost from the uterodome (pinopode) surface of the receptive human endometrium: in vitro evidence that MUC16 is a barrier to trophoblast adherence. Biol Reprod 78:134-142.
  15. Graham CH, Lysiak JJ, McCrae KR, Lala PK (1992) Localization of transforming growth factor-${\beta}$ at the human fetal-maternal interface: role in trophoblast growth and differentiation. Biol Reprod 46:561-572. https://doi.org/10.1095/biolreprod46.4.561
  16. Greening DW, Nguyen HP, Evans J, Simpson RJ, Salamonsen LA (2016) Modulating the endometrial epithelial proteome and secretome in preparation for pregnancy: The role of ovarian steroid and pregnancy hormones. J Proteomics 144:99-112. https://doi.org/10.1016/j.jprot.2016.05.026
  17. Hambartsoumian E (1998) Endometrial leukemia inhibitory factor (LIF) as a possible cause of unexplained infertility and multiple failures of implantation. Am J Reprod Immunol 39:137-143. https://doi.org/10.1111/j.1600-0897.1998.tb00345.x
  18. Hantak AM, Bagchi IC, Bagchi MK (2014) Role of uterine stromal-epithelial crosstalk in embryo implantation. Int J Dev Biol 58:139-146. https://doi.org/10.1387/ijdb.130348mb
  19. Hunkapiller NM, Gasperowicz M, Kapidzic M, Plaks V, Maltepe E, Kitajewski J, Cross JC, Fisher SJ (2011) A role for Notch signaling in trophoblast endovascular invasion and in the pathogenesis of pre-eclampsia. Development 138:2987-2998. https://doi.org/10.1242/dev.066589
  20. Iacob D, Cai J, Tsonis M, Babwah A, Chakraborty C, Bhattacharjee RN, Lala PK (2008) Decorin-mediated inhibition of proliferation and migration of the human trophoblast via different tyrosine kinase receptors. Endocrinology 149:6187-6197. https://doi.org/10.1210/en.2008-0780
  21. Kadokawa Y, Fuketa I, Nose A, Takeichi M, Nakatsuji N (1989) Expression pattern of E-and P-Cadherin in mouse embryos and uteri during the periimplantation period. Dev Growth Differ 31:23-30. https://doi.org/10.1111/j.1440-169X.1989.00023.x
  22. Karmakar S, Das C (2002) Regulation of trophoblast invasion by IL-$1{\beta}$ and TGF-${\beta}1$. Am J Reprod Immunol 48:210-219. https://doi.org/10.1034/j.1600-0897.2002.01151.x
  23. Kim M, Kim S, Chang SB, Yoo JS, Kim HK, Cho JH (2014) Effect of a mind-body therapeutic program for infertile women repeating in vitro fertilization treatment on uncertainty, anxiety, and implantation rate. Asian Nurs Res 8:49-56. https://doi.org/10.1016/j.anr.2014.02.002
  24. Klentzeris LD, Bulmer JN, Trejdosiewicz LK, Morrison L, Cooke ID (1993) Infertility: Beta-1 integrin cell adhesion molecules in the endometrium of fertile and infertile women. Hum Reprod 8:1223-1230. https://doi.org/10.1093/oxfordjournals.humrep.a138231
  25. Krussel JS, Bielfeld P, Polan ML, Simon C (2003) Regulation of embryonic implantation. Eur J Obstet Gynecol Reprod Biol 110:S2-S9. https://doi.org/10.1016/S0301-2115(03)00167-2
  26. Krege JH, Hodgin JB, Couse JF, Enmark E, Warner M, Mahler JF, Sar M, Korach KS, Gustafsson JA, Smithies O (1998) Generation and reproductive phenotypes of mice lacking estrogen receptor ${\beta}$. Proc Natl Acad Sci U S A 95:15677-15682. https://doi.org/10.1073/pnas.95.26.15677
  27. Laird SM, Tuckerman EM, Dalton CF, Dunphy BC, Li TC, Zhang X (1997) The production of leukaemia inhibitory factor by human endometrium: presence in uterine flushings and production by cells in culture. Hum Reprod 12:569-574. https://doi.org/10.1093/humrep/12.3.569
  28. Lee HR, Kim TH, Choi KC (2012) Functions and physiological roles of two types of estrogen receptors, $ER{\alpha}$ and $ER{\beta}$, identified by estrogen receptor knockout mouse. Lab Anim Res 28:71-76. https://doi.org/10.5625/lar.2012.28.2.71
  29. Lessey BA, Damjanovich L, Coutifaris C, Castelbaum A, Albelda SM, Buck CA (1992) Integrin adhesion molecules in the human endometrium. Correlation with the normal and abnormal menstrual cycle. J Clin Invest 90:188-195. https://doi.org/10.1172/JCI115835
  30. Lim H, Paria BC, Das SK, Dinchuk JE, Langenbach R, Trzaskos JM, Dey SK (1997) Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell 91:197-208. https://doi.org/10.1016/S0092-8674(00)80402-X
  31. Lubahn DB, Moyer JS, Golding TS, Couse JF, Korach KS, Smithies O (1993) Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc Natl Acad Sci USA 90:11162-11166. https://doi.org/10.1073/pnas.90.23.11162
  32. Lyall F (2006) Mechanisms regulating cytotrophoblast invasion in normal pregnancy and pre-eclampsia. Aust N Z J Obstet Gynaecol 46:266-273. https://doi.org/10.1111/j.1479-828X.2006.00589.x
  33. Lydon JP, DeMayo FJ, Funk CR, Mani SK, Hughes AR, Montgomery CA Jr, Shyamala G, Conneely OM, O' Malley BW (1995) Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Genes Dev 9:2266-2278. https://doi.org/10.1101/gad.9.18.2266
  34. Ma WG, Song H, Das SK, Paria BC, Dey SK (2003) Estrogen is a critical determinant that specifies the duration of the window of uterine receptivity for implantation. Proc Natl Acad Sci USA 100:2963-2968. https://doi.org/10.1073/pnas.0530162100
  35. Martel D, Frydman R, Glissant M, Maggioni C, Roche D, Psychoyos A (1987) Scanning electron microscopy of postovulatory human endometrium in spontaneous cycles and cycles stimulated by hormone treatment. J Endocrinol 114:319-324. https://doi.org/10.1677/joe.0.1140319
  36. McEwan M, Lins RJ, Munro SK, Vincent ZL, Ponnampalam AP, Mitchell MD (2009) Cytokine regulation during the formation of the fetal-maternal interface: Focus on cell-cell adhesion and remodelling of the extracellular matrix. Cytokine Growth Factor Rev 20:241-249. https://doi.org/10.1016/j.cytogfr.2009.05.004
  37. Mote PA, Arnett-Mansfield RL, Gava N, deFazio A, Mulac-Jericevic B, Conneely OM, Clarke CL (2006) Overlapping and distinct expression of progesterone receptors A and B in mouse uterus and mammary gland during the estrous cycle. Endocrinology 147:5503-5512. https://doi.org/10.1210/en.2006-0040
  38. Mulac-Jericevic B, Mullinax RA, DeMayo FJ, Lydon JP, Conneely OM (2000) Subgroup of reproductive functions of progesterone mediated by progesterone receptor-B isoform. Science 289:1751-1754. https://doi.org/10.1126/science.289.5485.1751
  39. Naeslund G, Lundkvist O, Nilsson BO (1980) Transmission electron microscopy of mouse blastocysts activated and growth-arrested in vivo and in vitro. Anat Embryol 159:33-48. https://doi.org/10.1007/BF00299253
  40. Navot D, Scott RT, Droesch K, Veeck LL, Liu HC, Rosenwaks Z (1991) The window of embryo transfer and the efficiency of human conception in vitro. Fertil Steril 55:114-118. https://doi.org/10.1016/S0015-0282(16)54069-2
  41. Nejatbakhsh R, Kabir-Salmani M, Dimitriadis E, Hosseini A, Taheripanah R, Sadeghi Y, Akimoto Y, Iwashita M (2012) Subcellular localization of L-selectin ligand in the endometrium implies a novel function for pinopodes in endometrial receptivity. Reprod Biol Endocrinol 10:46. https://doi.org/10.1186/1477-7827-10-46
  42. Nicola C, Chirpac A, Lala PK, Chakraborty C (2007) Roles of Rho guanosine 5'-triphosphatase A, Rho kinases, and extracellular signal regulated kinase (1/2) in prostaglandin E2-mediated migration of first-trimester human extravillous trophoblast. Endocrinology 149:1243-1251.
  43. Norwitz ER, Schust DJ, Fisher SJ (2001) Implantation and the survival of early pregnancy. N Engl J Med 345:1400-1408. https://doi.org/10.1056/NEJMra000763
  44. Paria BC, Huet-Hudson YM, Dey SK (1993a) Blastocyst's state of activity determines the "window" of implantation in the receptive mouse uterus. Proc Natl Acad Sci USA 90:10159-10162. https://doi.org/10.1073/pnas.90.21.10159
  45. Paria BC, Elenius K, Klagsbrun M, Dey SK (1999b) Heparin-binding EGF-like growth factor interacts with mouse blastocysts independently of ErbB1: a possible role for heparan sulfate proteoglycans and ErbB4 in blastocyst implantation. Development 126:1997-2005.
  46. Pollard JW, Hunt JS, Wiktor-Jedrzejczak W, Stanley ER (1991) A pregnancy defect in the osteopetrotic (opop) mouse demonstrates the requirement for CSF-1 in female fertility. Dev Biol 148:273-283. https://doi.org/10.1016/0012-1606(91)90336-2
  47. Psychoyos A (1986) Uterine receptivity for nidation. Ann N Y Acad Sci 476:36-42. https://doi.org/10.1111/j.1749-6632.1986.tb20920.x
  48. Quinn CE, Casper RF (2008) Pinopodes: a questionable role in endometrial receptivity. Hum Reprod Update 15:229-236. https://doi.org/10.1093/humupd/dmn052
  49. Raab G, Kover K, Paria BC, Dey SK, Ezzell RM, Klagsbrun M (1996) Mouse preimplantation blastocysts adhere to cells expressing the transmembrane form of heparin-binding EGF-like growth factor. Development 122:637-645.
  50. Ramathal CY, Bagchi IC, Taylor RN, Bagchi MK (2010). Endometrial decidualization: Of mice and men. Semin Reprod Med 28:17-26. https://doi.org/10.1055/s-0029-1242989
  51. Rao AJ, Ramachandra SG, Ramesh V, Krishnamurthy HN, Ravindranath N, Moudgal NR (2007) Establishment of the need for oestrogen during implantation in non-human primates. Reprod Biomed Online 14:563-571. https://doi.org/10.1016/S1472-6483(10)61047-4
  52. Rowlands TM, Symonds JM, Farookhi R, Blaschuk OW (2000) Cadherins: Crucial regulators of structure and function in reproductive tissues. Rev Reprod 5:53-61. https://doi.org/10.1530/ror.0.0050053
  53. Schatz F, Aigner S, Papp C, Toth-Pal E, Hausknecht V, Lockwood CJ (1995) Plasminogen activator activity during decidualization of human endometrial stromal cells is regulated by plasminogen activator inhibitor 1. J Clin Endocrinol Metab 80:2504-2510.
  54. Shimonovitz S, Hurwitz A, Dushnik M, Anteby E, Geva-Eldar T, Yagel S (1994) Developmental regulation of the expression of 72 and 92 kd type IV collagenases in human trophoblasts: A possible mechanism for control of trophoblast invasion. Am J Obstet Gynecol 171: 832-838. https://doi.org/10.1016/0002-9378(94)90107-4
  55. Simon C, Gimeno MJ, Mercader A, Frances A, Garcia Velasco J, Remohi J, Polan ML, Pellicer A (1996) Cytokines-adhesion molecules-invasive proteinases. The missing paracrine/autocrine link in embryonic implantation? Mol Hum Reprod 2:405-424. https://doi.org/10.1093/molehr/2.6.405
  56. Simon C, Garcia Velasco JJ, Valbuena D, Peinado JA, Moreno C, Remohi J, Pellicer A (1998) Increasing uterine receptivity by decreasing estradiol levels during the preimplantation period in high responders with the use of a follicle-stimulating hormone step-down regimen. Fertil Steril 70:234-239. https://doi.org/10.1016/S0015-0282(98)00140-X
  57. Stavreus-Evers A, Aghajanova L, Brismar H, Eriksson H, Landgren BM, Hovatta O (2002) Co-existence of heparin-binding epidermal growth factor-like growth factor and pinopodes in human endometrium at the time of implantation. Mol Hum Reprod 8:765-769. https://doi.org/10.1093/molehr/8.8.765
  58. Stewart CL, Kaspar P, Brunet LJ, Bhatt H, Gadi I, Kontgen F, Abbondanzo SJ (1992) Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nature 359:76-79. https://doi.org/10.1038/359076a0
  59. Strickland S, Reich E, Sherman MI (1976) Plasminogen activator in early embryogenesis: enzyme production by trophoblast and parietal endoderm. Cell 9:231-240. https://doi.org/10.1016/0092-8674(76)90114-8
  60. Surveyor GA, Gendler SJ, Pemberton L, Das SK, Chakraborty I, Julian J, Pimental RA, Wegner CC, Dey SK, Carson DD (1995) Expression and steroid hormonal control of Muc-1 in the mouse uterus. Endocrinology 136:3639-3647. https://doi.org/10.1210/endo.136.8.7628404
  61. Sutherland AE, Calarco PG, Damsky CH (1993) Developmental regulation of integrin expression at the time of implantation in the mouse embryo. Development 119:1175-1186.
  62. Takeichi M (1988) The cadherins: cell-cell adhesion molecules controlling animal morphogenesis. Development 102:639-655.
  63. Thie M, Harrach-Ruprecht B, Sauer H, Fuchs P, Albers A, Denker HW (1995) Cell adhesion to the apical pole of epithelium: a function of cell polarity. Eur J Cell Biol 66:180-191.
  64. Thomas K, De Hertogh R, Pizarro M, Van Exter C, Ferin J (1973) Plasma LH-HCG, 17-estradiol, estrone and progesterone monitoring around ovulation and subsequent nidation. Int J Fertil 18:65-73.
  65. Tsurudome M, Ito Y (2000) Function of fusion regulatory proteins (FRPs) in immune cells and virus-infected cells. Crit Rev Immunol 20:167-196.
  66. Van der Weiden RM, Helmerhorst FM, Keirse MJ (1991) Influence of prostaglandins and platelet activating factor on implantation. Hum Reprod 6:436-442. https://doi.org/10.1093/oxfordjournals.humrep.a137354
  67. Wang B, Sheng JZ, He RH, Qian YL, Jin F, Huang HF (2008) High expression of l-selectin ligand in secretory endometrium is associated with better endometrial receptivity and facilitates embryo implantation in human being. Am J Reprod Immunol 60:127-134. https://doi.org/10.1111/j.1600-0897.2008.00604.x
  68. Wilcox AJ, Baird DD, Weinberg CR (1999) Time of implantation of the conceptus and loss of pregnancy. N Engl J Med 1999:1796-1799.