Control of the Blastocyst Implantation For blastocyst implantation, interaction between the embryo and uterus is needed. This process involves the trophoblast cells interacting with the endometrium, and can only take place during the “implantation window” which spans from 20-24 days of the menstrual cycle. (4) Initially it is dependent on the levels of progesterone and estrogen, but later chemical signals from the embryo and the trophoblast lead to further morphological and biochemical changes. (4) At any other time, the epithelium of the uterus is covered by thick glycocalyx, a transmembrane glycoprotein that has an extended extracellular matrix which prevents blastocyst attachment. Blastocyst attachment to the uterine wall also depends upon the interaction between adhesion molecules expressed on both trophoblast cells and uterine epithelium. This interaction is mediated, in most cases, by bridging ligands which are released in the uterine cavity. (4) Control of Blastocyst Implantation Cytokines, small cell-signaling protein molecules used in intercellular communication, and chemokines, cytokines that act as a chemo-attractant to guide the migration of cells, both play a role in the control of the human blastocyst implantation. The molecular mechanisms of implantation involve “complex cascade-like interactions between the embryonic trophoblast cells, epithelial cell, decidual cell, cells responsible for immune reactions and the extra-cellular matrix (ECM) of the maternal endometrium.” (2) Decidual cells are enlarged cells found in the uterine mucous membrane and they specialize to provide the embryo with nutrients. The decidual cells and the endometrial glands, along with the embryo secrete growth and other factors that facilitate the implantation of the embryo. (2) “Moreover chemokines, interacting with G protein-coupled receptors, induce a structural change in integrins which favors adhesion of the blastocyst to the decidualized endometrium.” (4) The molecular interactions between the blastocyst and the uterus happen in three stages: 1) Signal exchange during the preimplantation 2) Adplantation: Interactions between the blastocyst and the uterine epithelium 3) Invasion of the trophoblast: Interactions between the blastocyst and the endometrium (2) 1. Signal Exchange during preimplantation Even before apposition, the embryo and the endometrium communicate. When the blastocyst emerges, it secretes molecules that affect the ovary, the fallopian tubes and the endometrium. Receptors appear on the blastocyst for factors such as the leukocyte inhibitory factor (LIF). The embryo also produces interleukin 1, a type of cytokine, which helps orient it toward the endometrium. During preimplantation, the density of glycocalyx (thick surface proteins), along with the electrostatic repulsion between the blastocyst and the endometrium, decreases and helps implantation. (2) 2. Adplantation: The Blastocyst and the Uterine Epithelium The apposition and the adhesion of the blastocyst require secretions of numerous factors such as interleukin 1 (IL-1), the inhibition factor for leukocytes (LIF) and the epithelial growth factor (EGF). These factors, secreted by either the blastocyst or the uterine epithelium, bind to receptors of the other tissue. (2) During implantation, LIF is made by the uterine epithelial cells and its receptors are on the blastocyst. “It appears to play a role in the differentiation of the CT to ST and assists HCG (human chorionic gonadotropin) secretion.” (2) The receptors for EGF are expressed by the blastocyst. However, these receptors appear in the inner cell mass and the trophoblast at different times, which explains the orientation of the blastocyst that causes it to embed in the endometrium with the appropriate side. (2) \ Cell Signaling in Adplantation 3. Invasion of the Trophoblast: The Blastocyst and the Endometrium The trophoblast infiltrates the endometrium by secreting enzymes that makes the extra cellular matrix (ECM) more porous, and by growing into the decidua of the uterine tissue, which is the uterine lining. (2) Trophoblast cells express certain cell adhesion molecules (integrins) on their membranes that interact with the uterine membrane. Endometrial factors greatly facilitate the growth of the trophoblast into the endometrium by using autocrine (self-signaling) and paracrine (chemical signaling) cells. These ease the invasion of the trophoblast. (2) Invasion of the Trophoblast Abnormal Implantation There can be many different causes for abnormal implantation. Besides the normal implantation zone, there are other locations, both within and outside the uterus, where the blastocyst can embed itself. This is called extra-uterine gravidity (EUG), where the fertilized egg settles outside the inner lining of the uterus. (3) “When the implantation takes place in the lower part of the uterus, the placenta will later develop in the cervix uteri” (“6.7 Brief Summary”). This type of implantation is called placenta previa, and it can lead to serious complications (hemorrhages). (3) Abnormal Implantation (ectopic pregnancy) Bibliography 1. "6.2 Implantation Stages." Implantation Stages. Web. 26 Feb. 2012. <http://www.embryology.ch/anglais/gnidation/etape02.html>. (1) 2. "6.3 Molecular Aspects of Implantation." Molecular Aspects of Implantation. Web. 26 Feb. 2012. <http://www.embryology.ch/anglais/gnidation/molecul01.html>. (2) 3. "6.7 Brief Summary." Brief Summary, Implantation. Web. 26 Feb. 2012. <http://www.embryology.ch/anglais/gnidation/resumenidation01.html>. (3) 4. "Blastocyst Implantation - Control of Human Trophoblast Function." Blastocyst Implantation. 8 Sept. 2008. Web. 26 Feb. 2012. <http://www.biologyonline.org/articles/control-human-trophoblast-function/blastocyst-implantation.html>. (4) 5. Campbell, Neil A., and Jane B. Reece. Biology. Sixth ed. Boston, MA: Pearson Custom/Benjamin Cummings, 2002. 637, 990. Print. 6. "Echinodermata." 302 Found. Web. 28 Feb. 2012. <http://tolweb.org/Echinodermata>. 7. "Molluscs." The Department of Zoology at Miami University. Web. 28 Feb. 2012. <http://zoology.muohio.edu/crist/Zoo312/Molluscs.html>. 8. Yeh, Jennifer. "Cephalization." Animal Sciences. 2002. Encyclopedia.com. 26 Feb. 2012 <http://www.encyclopedia.com>. Implantation: http://www.embryology.ch/anglais/gnidation/planmodnidation.html (Module 6 + Summary) Implantation video: http://embryology.med.unsw.edu.au/Medicine/BGDlab3_7.htm find video