Endometriyal Reseptivitenin İmplantasyondaki Rolü

Blastosist implantasyonu dinamik bir süreçtir. Bu süreç, embriyonun hazırlanmış endometriyum epiteline yaklaşmasını, tutunmasını ve endometriyal stromaya yayılmasını içerir. Başarılı bir implantasyon, blastosist ve reseptif endometriyum arasında karşılıklı etkileşimlerin sonucudur. Endometriyum, reseptif olana kadar belirli morfolojik değişiklikler geçirerek gelişir. Endometriyal reseptivite, in vitro fertilizasyon ve embriyo transferi tedavilerinin başarısında önemli bir sınırlama oluşturur. Diğer bir deyişle, embriyo gelişimi ve endometriyal olgunlaşma arasındaki bir uyum eksikliği, implantasyon başarısızlığının bir sebebidir. Blastosist sadece, endometriyumun benzersiz morfolojik ve moleküler değişiklikleriyle karakterize olan reseptif fazında implante olabilir. İmplantasyon boyunca, uterin boşluğa uzanan epitelyal hücrelerin apikal membranları mikrovillüslerini kaybeder, geniş ve düz membran uzantıları gelişir. Endometriyal yüzeydeki bu uzantılar implantasyon penceresinin ince yapı belirteçleri olarak tanımlanmıştır ve pinopodlar olarak bilinirler. Pinopod ekspresyonlarında değişimlerin eşlik edebildiği, bozulmuş veya prematür endometriyal olgunlaşma, IVF siklüslerinde implantasyon oranlarında azalmaya sebep olabilir. Dahası, maternal endometriyal hücreler; direk olarak ovaryan steroidlerle, indirek olarak çeşitli büyüme faktörleri ve sitokinlerle düzenlenirler. Blastosist implantasyonunu destekleyen endometriyum farklılaşması, progesteron ve östrojen tarafından ayarlanır. Yine de, blastosist implantasyonunda, endometriyum reseptivitesini sağlayan bu moleküler mekanizmalar tam olarak anlaşılmış değildir. Bu alandaki ileri çalışmalar yeni iyileştirici fırsatlar sunabilir.

Anahtar Kelimeler:

implantasyon, endometriyal reseptivite, pinopod

Endometriyal Reseptivitenin İmplantasyondaki Rolü

AbstractThe Role of Endometrial Receptivity in Implantation Blastocyst implantation is a dynamic process. This process involves embryo apposition and attachment to the prepared endometrial epithelium, and invasion into the endometrial stroma. Successful implantation is the result of reciprocal interactions between the blastocyst and receptive endometrium. The endometrium undergoes precisely defined morphological changes until receptive endometrium is developed. Endometrial receptivity represents a crucial limit for the success of in vitro fertilization and embryo transfer treatments. In other words a lack of synchrony between the embryo development and endometrial maturation results in an implantation failure. Blastocyst may implant only in the receptive phase, which is characterized by unique morphological and molecular changes of the endometrium. During implantation, the apical membranes of the epithelial cells lining the uterine cavity lose their microvilli and develop large and smooth membrane projections. These projections on the endometrial surface have been suggested as ultrastructural markers of the implantation window, which are known as pinopodes. Reduced implantation rates in IVF cycles could result from impaired or premature endometrial maturation, which could be accompanied by alterations in pinopode expression. Furthermore, maternal endometrial cells are regulated directly by ovarian steroids and indirectly by various growth factors and cytokines. Endometrial differentiation to support blastocyst implantation is coordinated by progesterone and oestrogen. Nevertheless, the molecular mechanisms that render the endometrium receptive to blastocyst implantation are not fully understood. Further research in this field may offer new therapeutic opportunities.

Keywords:

implantation, endometrial receptivity, pinopod,

PDF

___

Moore KL, Persaud TVN. Insan Gelişiminin Başlangıcı. Klinik Yönleriyle Insan Embriyolojisi, Altıncı Ingilizce Baskıdan Çeviri, Yıldırım M, Okar I, Dalçık H. İstanbul: Nobel Tıp Kitabevleri, 2002; 1-47.
Roos MH, Kaye GI, Pawlina W. Female Reproductive System. Histology a Text and Atlas with Cell and Molecular Biology, Fourth Ed. Baltimore: Williams&Wilkins, 2003;743—63.
İmplantasyon Sürecinde Endometriynm Strowitzki T, Germeyer A, Popovici R, Wolff M. The human endometrium as a fertility-determining factor. Hum ll. Giudice LC. Potential biochemical markers of uterine receptivity. Hum Reprod l999;14:3—16. Ledee-Bataille N, Lapree-Delage G, Taupin JL. Concentration of leukaemia inhibitory factor (LIF) in Tan BK, Vandekerckhove P, Kennedy R, Keay SD. Investigation and current management of recurrent IVF treatment failure in the UK. BJOG 2005;112:773—80.
Urman B,Yak1n K, Balaban B. Recurrent implantation failure in assisted reproduction: how to counsel and Haddad—Filho J, Cedenho AP, Katz SG. Endometrial expression of IL—lRtl in patients undergoing miscarriage or Hoozemans DA, Schats R, Lambalk CB, Homburg R, Hompes PGA. Human embryo implantation: current knowledge and clinical implications in assisted reproductive technology. Reprod Biomed Online ;9:692—715. Makrigiannakis A, Minas V. Mechanisms of implantation. Reprod Biomed Online 2007;14:102—9.
Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Am J Obstet Gynecol 1975;122(2):262-3.
Rogers P, Leeton J. Uterine receptivity and embryo transfer. Trounson AO, Gardner DK, Handbook of in vitro fertilization, 2 "d Ed. CRC Press. 2000;499—528.
Enders AC, Nelson DM. Pinocytotic activity of the uterus of the rat. Am JAnaI 1973;138:277—99.
Nardo LG, Sabatini L, Rai R and Nardo F. Pinopode expression during human implantation. Eur J Obstet Leach RE, Khalifa R, Armant R, Brudley A, Das SK, Dey SK, Fazleabas AT. Heparin—binding EGF—like growth Nikas G. Pinopodes as markers of endometrial receptivity in clinical practice. Hum Reprod 1999; 14: 99-106.
Nikas G, Aghajanova L. Endometrial pinopodes: some more understanding on human implantation? Reprod Develioglu OH, Nikas G, Hsiu JG, Toner JP, Jones HW. Detection of endometrial pinopodes by light microscopy. Stavreus—Evers A. Nikas G, Sahlin L, Eriksson H, Landgren B—M. Formation of pinopodes in human Nikas G, Psychoyos A. Uterin pinopodes as markers of uterine receptivity. Assist Reprod Rev 1994;4226—32.
Nikas G, Psychoyos A. Uterine pinopods in peri— implantation human endometrium. Clinical relevance. Ann Lessey BA. Two pathways of progesterone action in the human endometrium: implications for implantation and Creus M, Ordi J, Fabregues F, Casamitjana R, Carmona F, Cardesa A, Vanrell JA and Balasch J. The effect of different hormone therapies on integrin expression and pinopode formation in the human endometrium: a controlled study. Hum Reprod 2003;18:683—93.
Defrere S, Van Langendonckt A, Moulin P, Befahy P, Thathiah A and Carson DD. MTl—MMP mediates MUCl shedding independent of TACE/ADAM17. Biochem J Dimitriadis E, White CA, Jones RL, Salamonsen LA. Cytokines, chemokines and growth factors in endometrium Kondera—Anasz Z, Sikora J, Mielczarek—Palacz A, Jonca M. Concentrations of interleukin (IL)—1 alpha, IL—l soluble receptor type II (IL—1 sRII) and IL—1 receptor antagonist (IL—1 Ra) in the peritoneal şuid and serum of infertile women with endometriosis. Eur J Obstet Gynecol Reprod Bio 2005;123:198-203.
Huang JC, Wun WSA, Goldsby JS, Wun IC, Noorhasan D, Wu KK. Stimulation of embryo hatching and implantation Ye X, Hama K. LPA3-mediated lysophosphatidic acid signalling in embriyo implantation and spacing. Nature Horne AW, White JO, Lalani EN. The endometrium and embryo implantation. BMJ 2000;321:1301—2.
Edwards RG. Human Implantation: the last barrier in assisted reproduction technologies? Reprod Biomed Online ;13:887-904.