Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
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Role of Trophobolast in Implantation and Placenta Development

착상 및 태반 발달과정에 따른 영양막세포의 역할

  • Kim, Gi-Jin (Department of Biomedical Science, CHA University School of Medicine)
  • 김기진 (차의과학대학교 의생명과학과)
  • Received : 2010.09.07
  • Accepted : 2010.09.20
  • Published : 2010.09.30
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Abstract

The placenta, which is a temporary organ derived from the fetus during pregnancy, is critical to support fetus development via optimal regulation between mother and fetus. Trophoblast as a major cell population of the placenta is one of the earliest to differentiate and shows an extensive proliferation or/and differentiation up to the formation of the placenta. The role of the trophoblast show dynamic changes from early embryo implantation to placentation during pregnancy. Implantation of the blastocyst into the endometrium of the maternal uterus is mediated by invasion of the differentiated trophoblast (e.g. syncytiotrophoblast) from the trophectoderm. During pregnancy, the unique role of the trophoblast is to invasion, eroding, and metastasizing in the placenta as well as to ensure appropriate bidirectional nutrient or waste flow required for growth and maturation of the embryo. The dysfunction of the trophoblast during pregnancy can result in several gynecological diseases including preeclampsia and congenital malformation in neonatal medicine. Therefore, trophoblasts act as a conclusive factor in placental and fetal development. This brief review outlines the classification of trophoblast and its function in the placenta during pregnancy. Also, we introduce the latest research in trophoblast for implantation and the placenta development, and the application potential of trophoblast for infertility and obstetrical diseases.

태반 (placenta)은 임신기간 동안에만 존재하는 태아유래 일시적인 기관으로, 모체와 태아간의 정확한 조절 기전을 통해 태아의 발달을 수행하는 중요한 기관이다. 영양막세포 (trophoblast)는 임신 초기 빠른 분열 및 분화 과정을 거쳐 태반을 형성하는 주요 세포이다. 영양막세포의 역할은 초기 배아 착상 시기부터 40주간의 임신기간 동안 태반의 형성 과정에서 다양하게 변화된다. 착상은 모체 자궁내막층으로의 포배의 가장 밖에 존재하는 분화된 영양막세포(예, 합포영양막세포)의 침윤에 의해 이루어진다. 또한, 영양막세포은 임신기간 동안 배아의 성숙과 발달에 필요한 영양분과 노폐물 등을 모체와 태아 양방향으로 적절하게 전달할 뿐 아니라 태반 내에서 침윤과 다양한 물질들의 합성 혹은 분비에 관련된 대사작용에 관여한다. 이 기간 동안 영양막세포의 기능 이상은 태아의 선천적인 기형뿐 아니라 자간전증 등을 포함하는 다양한 산과질환을 유발하기도 한다. 그러므로, 영양막세포는 태반과 태아의 발달에 결정적인 요인으로 작용한다. 본 고찰에서는 다양한 영양막세포들의 기능을 이해하기 위해 분류 및 그 종류별 특징 등을 살펴보고, 착상 단계와 태반 발달에 따른 영양막세포의 고유한 역할에 대해 알아보고 향후 활용될 수 있는 연구 분야에 대해 알아보고자 한다.

Keywords

References

  1. Moore KL, Persaud TVN, Torchia MG. The developing human: clinically or ientated embryology. 8th ed. Philadelphia: Elsevier Saunders; 2008.
  2. Craven CM, Zhao L, Ward K. Lateral placental growth occurs by trophoblast cell invasion of decidual veins. Placenta 2000; 21: 160-9. https://doi.org/10.1053/plac.1999.0449
  3. Benirschke K, Kaufmann P. Pathology of the human placenta. 4th ed. New York: Springer Verlag; 2000.
  4. Spitalieri P, Cortese G, Pietropolli A, Filareto A, Dolci S, Klinger FG, et al. Identification of multipotent cytotrophoblast cells from human first trimester chorionic villi. Cloning Stem Cells 2009; 11: 535-56. https://doi.org/10.1089/clo.2009.0046
  5. Harris LK. Review: Trophoblast-vascular cell interactions in early pregnancy: how to remodel a vessel. Placenta 2010; 31(Suppl): S93-8. https://doi.org/10.1016/j.placenta.2009.12.012
  6. Jeon SY, Lee HJ, Park JM, Jung HM, Yoo JK, Lee JS, et al. Increased immortalization-upregulated protein 2 (IMUP-2) by hypoxia induces apoptosis of the trophoblast and pre-eclampsia. J Cell Biochem 2010; 110: 522-30.
  7. Morrish DW, Dakour J, Li H. Life and death in the placenta: new peptides and genes regulating human syncytiotrophoblast and extravillous cytotrophoblast lineage formation and renewal. Curr Protein Pept Sci 2001; 2: 245-59. https://doi.org/10.2174/1389203013381116
  8. Lunghi L, Ferretti ME, Medici S, Biondi C, Vesce F. Control of human trophoblast function. Reprod Biol Endocrinol 2007; 5: 6. https://doi.org/10.1186/1477-7827-5-6
  9. Caniggia I, Taylor CV, Ritchie JW, Lye SJ, Letarte M. Endoglin regulates trophoblast differentiation along the invasive pathway in human placental villous explants. Endocrinology 1997; 138: 4977-88. https://doi.org/10.1210/en.138.11.4977
  10. Adjaye J, Huntriss J, Herwig R, BenKahla A, Brink TC, Wierling C, et al. Primary differentiation in the human blastocyst: comparative molecular portraits of inner cell mass and trophectoderm cells. Stem Cells 2005; 23: 1514-25. https://doi.org/10.1634/stemcells.2005-0113
  11. Lash GE, Otun HA, Innes BA, Percival K, Searle RF, Robson SC, et al. Regulation of extravillous trophoblast invasion by uterine natural killer cells is dependent on gestational age. Hum Reprod 2010; 25: 1137-45. https://doi.org/10.1093/humrep/deq050
  12. Gonen-Gross T, Goldman-Wohl D, Huppertz B, Lankry D, Greenfield C, Natanson-Yaron S, et al. Inhibitory NK receptor recognition of HLA-G: regulation by contact residues and by cell specific expression at the fetal-maternal interface. PLoS One 2010; 5: e8941. https://doi.org/10.1371/journal.pone.0008941
  13. Clark DA, Chaouat G, Wong K, Gorczynski RM, Kinsky R. Tolerance mechanisms in pregnancy: a reappraisal of the role of class I paternal MHC antigens. Am J Reprod Immunol 2010; 63: 93-103.
  14. Red-Horse K, Zhou Y, Genbacev O, Prakobphol A, Foulk R, McMaster M, et al. Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface. J Clin Invest 2004; 114: 744-54. https://doi.org/10.1172/JCI200422991
  15. Blomberg L, Hashizume K, Viebahn C. Blastocyst elongation, trophoblastic differentiation, and embryonic pattern formation. Reproduction 2008; 135: 181-95. https://doi.org/10.1530/REP-07-0355
  16. Franchi A, Zaret J, Zhang X, Bocca S, Oehninger S. Expression of immunomodulatory genes, their protein products and specific ligands/receptors during the window of implantation in the human endometrium. Mol Hum Reprod 2008; 14: 413-21. https://doi.org/10.1093/molehr/gan029
  17. Caniggia I, Winter J, Lye SJ, Post M. Oxygen and placental development during the first trimester: implications for the pathophysiology of pre-eclampsia. Placenta 2000; 21(Suppl A): S25-30. https://doi.org/10.1053/plac.1999.0522
  18. James JL, Stone PR, Chamley LW. The regulation of trophoblast differentiation by oxygen in the first trimester of pregnancy. Hum Reprod Update 2006; 12: 137-44. https://doi.org/10.1093/humupd/dmi043
  19. Dubinsky V, Poehlmann TG, Suman P, Gentile T, Markert UR, Gutierrez G. Role of regulatory and angiogenic cytokines in invasion of trophoblastic cells. Am J Reprod Immunol 2010; 63: 193-9.
  20. Jovanovic M, Stefanoska I, Radojcic L, Vicovac L. Interleukin- 8 (CXCL8) stimulates trophoblast cell migration and invasion by increasing levels of matrix metalloproteinase (MMP)2 and MMP9 and integrins alpha5 and beta1. Reproduction 2010; 139: 789-98. https://doi.org/10.1530/REP-09-0341
  21. Isaka K, Usuda S, Ito H, Sagawa Y, Nakamura H, Nishi H, et al. Expression and activity of matrix metalloproteinase 2 and 9 in human trophoblasts. Placenta 2003; 24: 53-64. https://doi.org/10.1053/plac.2002.0867
  22. Fitzgerald JS, Poehlmann TG, Schleussner E, Markert UR. Trophoblast invasion: the role of intracellular cytokine signalling via signal transducer and activator of transcription 3 (STAT3). Hum Reprod Update 2008; 14: 335-44. https://doi.org/10.1093/humupd/dmn010
  23. Grazul-Bilska AT, Borowicz PP, Johnson ML, Minten MA, Bilski JJ, Wroblewski R, et al. Placental development during early pregnancy in sheep: vascular growth and expression of angiogenic factors in maternal placenta. Reproduction 2010; 140: 165-74. https://doi.org/10.1530/REP-09-0548
  24. Reynolds LP, Grazul-Bilska AT, Redmer DA. Angiogenesis in the female reproductive organs: pathological implications. Int J Exp Pathol 2002; 83: 151-63. https://doi.org/10.1046/j.1365-2613.2002.00277.x
  25. Shih IM, Kurman RJ. The pathology of intermediate trophoblastic tumors and tumor-like lesions. Int J Gynecol Pathol 2001; 20: 31-47. https://doi.org/10.1097/00004347-200101000-00004
  26. Brosens IA. Morphological changes in the utero-placental bed in pregnancy hypertension. Clin Obstet Gynaecol 1977; 4: 573-93.
  27. Whitley GS, Dash PR, Ayling LJ, Prefumo F, Thilaganathan B, Cartwright JE. Increased apoptosis in first trimester extravillous trophoblasts from pregnancies at higher risk of developing preeclampsia. Am J Pathol 2007; 170: 1903-9. https://doi.org/10.2353/ajpath.2007.070006
  28. Verlohren S, Geusens N, Morton J, Verhaegen I, Hering L, Herse F, et al. Inhibition of trophoblast-induced spiral artery remodeling reduces placental perfusion in rat pregnancy. Hypertension 2010; 56: 304-10. https://doi.org/10.1161/HYPERTENSIONAHA.110.153163
  29. Dekker GA, Sibai BM. Etiology and pathogenesis of preeclampsia: current concepts. Am J Obstet Gynecol 1998; 179: 1359-75. https://doi.org/10.1016/S0002-9378(98)70160-7
  30. Kalkunte S, Lai Z, Norris WE, Pietras LA, Tewari N, Boij R, et al. Novel approaches for mechanistic understanding and predicting preeclampsia. J Reprod Immunol 2009; 83: 134-8. https://doi.org/10.1016/j.jri.2009.08.006
  31. Apps R, Murphy SP, Fernando R, Gardner L, Ahad T, Moffett A. Human leucocyte antigen (HLA) expression of primary trophoblast cells and placental cell lines, determined using single antigen beads to characterize allotype specificities of anti-HLA antibodies. Immunology 2009; 127: 26-39. https://doi.org/10.1111/j.1365-2567.2008.03019.x
  32. Li C, Houser BL, Nicotra ML, Strominger JL. HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells. Proc Natl Acad Sci USA 2009; 106: 5767-72. https://doi.org/10.1073/pnas.0901173106
  33. Carter AM. Animal models of human placentation: a review. Placenta 2007; 28(Suppl A): S41-7. https://doi.org/10.1016/j.placenta.2006.11.002
  34. Beghin D, Delongeas JL, Claude N, Farinotti R, Forestier F, Gil S. Comparative effects of drugs on P-glycoprotein expression and activity using rat and human trophoblast models. Toxicol In Vitro 2010; 24: 630-7. https://doi.org/10.1016/j.tiv.2009.10.005
  35. Oda M, Shiota K, Tanaka S. Trophoblast stem cells. Methods Enzymol 2006; 419: 387-400. https://doi.org/10.1016/S0076-6879(06)19015-1
  36. Harun R, Ruban L, Matin M, Draper J, Jenkins NM, Liew GC, et al. Cytotrophoblast stem cell lines derived from human embryonic stem cells and their capacity to mimic invasive implantation events. Hum Reprod 2006; 21: 1349-58. https://doi.org/10.1093/humrep/del017