EMBRİYO İMPLANTASYONUNUN MOLEKÜLER MEKANİZMASI

Yıl 2019, Cilt: 5 Sayı: 4, 311 - 322, 30.12.2019

Miyase Erdoğan , Elvan Şahin , Seher Dinçel

Öz

İnsan embriyosunun uterus duvarına implantasyonu, blastosist ve reseptif
endometriyum arasındaki karşılıklı etkileşim sonucu gerçekleşir.
Fertilizasyondan yaklaşık 6-7 gün sonra implantasyon başlar. İmplantasyonun
meydana gelebileceği uygun olgunluk düzeyine ulaşmak için, hem blastosist hem
de uterus birbirine paralel olarak farklılaşmalıdır.  Trofoekdoterm (TE)
ile uterus yüzeyini kaplayan lüminal epitel (LE) arasındaki etkileşim,
implantasyonu başlatır. TE ve LE arasındaki ilk bağlantıda bir dizi hücre-yüzey
molekülü rol alır. Bu bileşenlerin rolüne dair kanıtlar tartışmalıdır. Biz de
çalışmamızda implantasyon olayının tüm aşamalarında hangi sinyalizasyon
ağlarının rol aldığını ve implantasyon esnasında meydana gelen olayların
mekanizmalarını moleküler düzeyde literatür bilgisi ışığında derlemeyi
amaçladık.

Anahtar Kelimeler

Embriyonik implantasyon, uterus reseptivitesi, hücre yüzey molekülleri, endometriyal sitokinler

MOLECULAR MECHANISM OF EMBRIONIC IMPLANTATION

Öz

The implantation of the human embryo into
the uterine wall results from the interaction between the blastocyst and the
receptive endometrium. Approximately 6-7 days after fertilization, implantation
begins. Both the blastocyst and the uterus must be differentiated in parallel
to achieve the proper maturity at which implantation can occur. The interaction
between trophoecdotherm (TE) and the luminal epithelium (LE) covering the
uterine surface initiates implantation. A number of cell-surface molecules are
involved in the initial connection between TE and LE. Evidence of the role of
these components is controversial. In this study, we aimed to review which
signaling networks are involved in all stages of implantation and the
mechanisms of events occurring during implantation in the light of the
literature.

Anahtar Kelimeler

Embryonic implantation, uterine reseptivity, cell surface molecules, endometrial cytokines

Kaynakça

• 1. Ercan C. M., Ceyhan S.T. Endometriyal Reseptivitede Güncel Durum. TSRM Üreme sağlığı ve infertilite derneği. [Internet] Avaible from: https://www.tsrm.org.tr/pro/egitim/tsrm-derlemeler/endometriyal-reseptivitede-guncel-durum
• 2. Lessey BA, Killam AP, Metzger DA, Haney AF, Greene GL, McCarty KS Jr. Immunohistochemical analysis of human uterine estrogen and progesterone receptors throughout the menstrual cycle. The Journal of Clinical Endocrinology & Metabolism. 1988;67(2): 334-340.
• 3. Gedikli S, Özbek E, Demirci T. Fertilizasyonun Moleküler Temeli. Van Tıp Dergisi. 2013;20(4): 294-301. 4. Sadler TW. Langman’s Medical Embryology. 12th ed., Lippincott Williams & Wilkins. 2012, p. 235-259.
• 5. Şahin E. Sakarya Üniversitesi Tıp Fakültesi, Genel Embriyoloji Ders Notları. 2018.
• 6. Günalp S. Tuncer S. Kadın Hastalıkları ve Doğum Tanı ve Tedavi. Pelikan Yayınları. 2004.
• 7. Otlu A. İnönü Üniversitesi Tıp Fakültesi Histoloji ve Embriyoloji Ders Notları.2015.
• 8. Hoffman BL, Schorge JO, Schaffer JI, Halvorson LM, Bradshaw K,Cunningham FG. Williams Jinekoloji. Çeviri editörleri: Gökhan Yıldırım, Gonca Yetkin Yıldırım, İbrahim Polat. 2.Baskı. Nobel Tıp Kitabevleri. 2015.
• 9. Atasü T. Şahmay S. Jinekoloji/Kadın hastalıkları. Üniversal Dil Hizmetleri Yayıncılık.1996.
• 10. Ross MH, Pawlina W. Histoloji Konu Anlatımı ve Atlas. Çeviri editörü: Barış Baykal. 6.baskı. Palme yayıncılık. 2013; sayfa: 484-984.
• 11. Kierszenbaum A.L. Histoloji ve Hücre Biyolojisi-Patolojiye Giriş. Palme Yayıncılık. 2006; 232-605.
• 12. Kimber SJ. Molecular interactions at the maternal-embryonic interface during the early phase of implantation. Seminars Reproduction Medicine. 2000;18(3): 237-53.
• 13. Emiliani S. Delbaero A. Devreker F. Englert Y. Embryo–maternal interactive factors regulating the implantation process: implications in assisted reproductive. Reproductive biomedicine online. 2005;10(4): 527-540.
• 14. De Los Santos MJ, Mercader A, Galán A, Albert C, Romero JL, Pellicer A. Implantation rates after two, three or five days of embryo culture. Placenta. 2003;24: 13-19.
• 15. Sharma A. Kumar P. Understanding implantation window, a crucial phenomenon. Journal of Human Reproductive Sciences. 2012;5(1): 2-6.
• 16. Çolgar U. Reprodüktif Endokrinoloji ve İnfertilite. İstanbul Medikal Yayıncılık, 2006.
• 17. Gardner DK, Weissman A, Howles CM, Shoham Z. Yardımla Üreme Teknikleri Temel Kitabı. Nobel Tıp Kitabevleri, 2010.
• 18. Aplin JD, Ruane PT. Embryo-epithelium interactions during implantation at a glance. Journal of Cell Science. 2017;130(1): 15-22.
• 19. Aplin JD. Adhesion molecules in implantation. Reviews of Reproduction. 1997;2(2): 84-93.
• 20. Clemmons, DR,Maile LA. Interaction between insulin-like growth factor-I receptor and αvβ3 integrin linked signaling pathways: cellular responses to changes in multiple signaling inputs. Molecular Endocrinology. 2005;19(1): 1-11.
• 21. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York. Garland Science. 2002.
• 22. Mangale SS, Reddy KVR. Expression pattern of integrins and their ligands in mouse feto-maternal tissues during pregnancy. Reproduction, Fertility and Development. 2007;19(3), 452–460.
• 23. Cruse JM, Lewis RE, Wang H. Molecules,cells and tissues of immunity. Immunology Guidebook. Elsevier Academic Press, 1st ed, 2004.
• 24. Shih IeM, Hsu MY, Oldt RJ 3rd, Herlyn M, Gearhart JD, Kurman RJ. The Role of E-cadherin in the Motility and Invasion of Implantation Site Intermediate Trophoblast. Placenta. 2002;23(10): 706-715.
• 25. Ley K. The role of selectins in inflammation and disease. Trends in Moleküler Medicine. 2003;9(6): 263-268.
• 26. Ganesh A, Chauhan N, Das S, Chakravarty B, Chaudhury K. Endometrial receptivity markers in infertile women stimulated with letrozole compared with clomiphene citrate and natural cycles. System Biology Reproductive Medicine . 2015;60(2): 105–111.
• 27. Cook-Miles JM. VCAM-1 signals during lymphocyte migration:Role of reactive oxygen species. Molecular Immunology. 2002; 39: 499-508.
• 28. Stolpe A, Saag PT. Intercellular adhesion molecule-1. Journal of Molecular Medicine. 1996;74:13–33.
• 29. Singh H,Aplin JD. Adhesion molecules in endometrial epithelium: tissue integrity and embryo implantation. Journal of Anatomy. 2009; 215(1): 3–13.
• 30. Cameo P.Srisuparp S.Strakova Z.Fazlaebas A. Chorionic gonadotropin and uterine dialogue in the primate.Reproductive Biology and Endocrinology. 2004;2(50).
• 31. Fritz MA,Speroff L. Klinik Jinekolojik Endokrinoloji ve İnfertilite. Güneş Tıp Kitabevleri. 8.baskı.2013.
• 32. Chakraborty I, Das SK, Wang J, Dey SK. Developmental expression of the cyclo-oxygenase-1 and cyclo-oxygenase-2 genes in the peri-implantation mouse uterus and their differential regulation by the blastocyst and ovarian steroids. Journal of Moleculer Endocrinology. 1996;16(2): 107-122.
• 33. Smith WL, Dewitt DL. Prostaglandin endoperoxide H synthases-1 and -2. Advances in Immunology.1996;62: 167–215.
• 34. Paulesu L, Letta F, Petraglia F. Feto-maternal biology and ethics of human society. Reproductive Biology and Endocrinology. 2005;3(55).
• 35. Aghajanova L. Leukemia inhibitory factor and human embryo implantation. Annals of the New York Academy of Sciences. 2004;1034: 176-183.
• 36. Şentürk LM, Arıcı A. Leukemia inhibitory factor in human reproduction. American Journal of Reproductive İmmunology. 1998;39(2): 144-151.
• 37. Daikoku T, Song H, Guo Y, Riesewijk A, Mosselman S, Das SK, et al.. Uterine Msx-1 and Wnt4 Signaling Becomes Aberrant in Mice with the Loss of Leukemia Inhibitory Factor or Hoxa-10: Evidence for a Novel Cytokine-Homeobox-Wnt Signaling in Implantation. Molecular Endocrinology. 2004;18(5): 1238-1250.
• 38. Hambartsoumian E. Endometrial leukemia inhibitory factor (LIF) as a possible cause of unexplained infertility and multiple failures of implantation. American Journal of Reproductive Immunology. 1998;39(2):137-143.
• 39. Aikawa S, Kano K, Inoue A, Wang J, Saigusa D, Nagamatsu T, et al. Autotaxin-lysophosphatidic acid-LPA3 signaling at the embryo-epithelial boundary controls decidualization pathways. The EMBO Journal. 2017;36(14):2146-2160.
• 40. Hama K, Aoki J, Bandoh K, Inoue A, Endo T, Amano T, et al. Lysophosphatidic receptor, LPA3, is positively and negatively regulated by progesterone and estrogen in the mouse uterus. Life Sciences. 2006;79: 1736–1740.
• 41. O’Neill C. The role of paf in embryo physiology. Human Reproduction Update. 2005;11(3): 215–228.
• 42. Nishi O, Tominaga T, Goto Y, Hayashi K, Mori T. Effects of Platelet Activating Factor on Mouse Embryo Implantation in Vitro. Journal of Assisted Reproduction and Genetics, Vol. 12, No. 5, 1995;12(5): 330-334.
• 43. Roudebush WE, Wininger JD, Jones AE, Wright G, Toledo AA, Kort HI, et al. Embryonic platelet-activating factor: an indicator of embryo viability. Human Reproduction. 2002;17(5): 1306-1310.
• 44. Fukuda AI, Breuel KF. Effect of platelet activating factor on embryonic development and implantation in the Mouse. Human Reproduction. 1996;11(12): 2746-2749.