Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-848d4c4894-2xdlg Total loading time: 0 Render date: 2024-07-02T21:47:31.427Z Has data issue: false hasContentIssue false

5 - Molecular Mechanisms of Implantation

from PART I - PHYSIOLOGY OF REPRODUCTION

Published online by Cambridge University Press:  04 August 2010

By
F. Domínguez ,
Carlos Simón  and
Juan A. Garcia-Velasco
Edited by
Botros R. M. B. Rizk ,
Juan A. Garcia-Velasco ,
Hassan N. Sallam  and
Antonis Makrigiannakis
Botros R. M. B. Rizk
Affiliation:
University of South Alabama
Juan A. Garcia-Velasco
Affiliation:
Rey Juan Carlos University School of Medicine,
Hassan N. Sallam
Affiliation:
University of Alexandria School of Medicine
Antonis Makrigiannakis
Affiliation:
University of Crete
Get access

Summary

INTRODUCTION

Successful implantation requires a functionally normal embryo at the blastocyst stage and a receptive endometrium, while a communication link between them is also vital. This process is a highly regulated mechanism with the involvement of many systems at the paracrine-autocrine levels. Not only human implantation needs this kind of dialogue, but also in other species, like mouse or primates, this cross-communication has been described before (1, 2).

During apposition, human blastocysts find a location to implant, in a specific area of the maternal endometrium. In the adhesion phase, which occurs six to seven days after ovulation, within the “implantation window,” direct contact occurs between the endometrial epithelium (EE) and the trophoectoderm (TE). Finally, in the invasion phase, the embryonic trophoblast breaches the basement membrane, invading the endometrial stroma and reaching the uterine vessels.

The EE is a monolayer of cuboidal cells that covers the interior of the uterus. As a reproductive tract mucosal barrier, EE must provide continuous protection against pathogens that gain access to the uterine cavity, while allowing embryonic implantation, a unique event crucial for the continuation of the species in mammals. Initial adhesion of the TE of the embryo to the EE plasma membrane is the prerequisite for implantation and placental development. EE is a specialized hormonally regulated cell population that must undergo cyclical morphological and biochemical changes to maintain an environment suitable for preimplantation embryonic development.

Keywords

chemokinesDNA microarrays technologyembryo implantationendometrial receptivityleukocyte transendothelial migrationgene regulation
Type
Chapter
Information
Infertility and Assisted Reproduction , pp. 46 - 52
Publisher: Cambridge University Press
Print publication year: 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Paria, BC, Song, H, Dey, SK. Implantation: molecular basis of embryo-uterine dialogue. Int J Dev Biol 2001;45(3):597–605.Google ScholarPubMed
Cameo, P, Srisuparp, S, Strakova, Z, et al. Chorionic gonadotropin and uterine dialogue in the primate. Reprod Biol Endocrin 2004;2:50.CrossRefGoogle ScholarPubMed
Kelner, GS, Kennedy, J, Bacon, KB, et al. Lymphotactin: a novel cytokine which represents a new class of chemokine. Science 1994;266:1395–9.CrossRefGoogle ScholarPubMed
Vaddi, K, Keller, M, Newton, RC. The chemokine fact book. London: Academic Press, 1997.Google Scholar
Horuk, R, Peiper, SC. Chemokines: molecular double agents. Curr Biol 1996;6:1581–2.CrossRefGoogle ScholarPubMed
Cocchi, F, DeVico, AL, Garzino-Demo, A, et al. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science 1995;270: 1811–15.CrossRefGoogle ScholarPubMed
Simón, C, Caballero-Campo, P, García-Velasco, JA, et al. Potential implications of chemokines in the reproductive function: an attractive idea. J Reprod Immunol 1998;38:169–93.CrossRefGoogle Scholar
Robertson, SA, Mayrhofer, G, Seamark, RF. Ovarian steroid hormones regulate granulocyte-macrophage colony-stimulating factor synthesis by uterine epithelial cells in the mouse. Biol Reprod 1996;54:265–77.CrossRefGoogle ScholarPubMed
Dudley, DJ, Trantman, MS, Mitchel, MD. Inflammatory mediators regulate interleukin-8 production by cultured gestational tissues: evidence for a cytokine network at the chorio-decidual interface. J Clin Endocrinol Metab 1993;76:404–10.Google ScholarPubMed
Arici, A, Seli, E, Senturk, LM, et al. Interleukin-8 in the human endometrium. J Clin Endocrinol Metab 1998;83:1783–7.Google ScholarPubMed
King, A, Loke, Y. Uterine large granular lymphocytes: a possible role in embryonic implantation. Am J Obstet Gynecol 1990;162: 308–10.CrossRefGoogle ScholarPubMed
Colditz, LG. Effects of exogenous prostaglandins E2 and actinomycin D on plasma leakage induced by neutrophil activating peptidel-interleukin-8. Immunol Cell Biol 1990;68:397–403.CrossRefGoogle Scholar
Kelly, RW, Illingworth, P, Baldie, G, et al. Progesterone control of IL-8 production in endometrium and chorio-decidual cells underlines the role of the neutrophil in menstruation and parturition. Hum Reprod 1994;9:253–8.CrossRefGoogle ScholarPubMed
Robertson, SA, Mau, VJ, Tremellen, KP, et al. Role of high molecular weight seminal vesicle proteins in eliciting the uterine inflammatory response to semen in mice. J Reprod Fertil 1996; 107:265–77.CrossRefGoogle ScholarPubMed
Choudhuri, R, Wood, GW. Determination of the number and distribution of macrophages, lymphocytes and granulocytes in the mouse uterus from mating through implantation. J Leukoc Biol 1991;50:252–62.Google Scholar
Caballero-Campo, P, Dominguez, F, Coloma, J, et al. Hormonal and embryonic regulation of chemokines IL-8, MCP-1 and RANTES in the human endometrium during the window of implantation. Mol Hum Reprod 2002;8(4):375–84.CrossRefGoogle ScholarPubMed
Dominguez, F, Galan, A, Martin, JJ, et al. Hormonal and embryonic regulation of chemokine receptors CXCR1, CXCR4, CCR5 and CCR2B in the human endometrium and the human blastocyst. Mol Hum Reprod 2003;9:189–98.CrossRefGoogle ScholarPubMed
Nagaoka, K, Nojima, H, Watanabe, F, et al. Regulation of blastocyst migration, apposition, and initial adhesion by a chemokine, interferon gamma-inducible protein 10 kDa (IP-10), during early gestation. J Biol Chem 2003;278:29048–56.CrossRefGoogle Scholar
Shufaro, Y, Nadjari, M. Implantation of a gestational sac in a cesarean section scar. Fertil Steril 2001;75:1217.CrossRefGoogle Scholar
Dominguez, F, Yanez-Mo, M, Sanchez-Madrid, F, et al. Embryonic implantation and leukocyte transendothelial migration: different processes with similar players?FASEB J 2005;19(9):1056–60.CrossRefGoogle ScholarPubMed
Genbacev, OD, Prakobphol, A, Foulk, RA, et al. Trophoblast L-selectin-mediated adhesion at the maternal-fetal interface. Science 2003;299:405–8.CrossRefGoogle ScholarPubMed
Thie, M, Denker, HW, et al. In vitro studies on endometrial adhesiveness for trophoblast: cellular dynamics in uterine epithelial cells. Cells Tiss Organs 2002;172(3):237–52.CrossRefGoogle ScholarPubMed
Paria, BC, Reese, J, Das, SK, Dey, SK. Deciphering the cross-talk of implantation: advances and challenges. Science 2002;296: 2185–8.CrossRefGoogle ScholarPubMed
Moser, B, Loetscher, P. Lymphocyte traffic control by chemokines. Nat Immunol 2001;2:123–8.CrossRefGoogle ScholarPubMed
Ley, K, Kansas, GS. Selectins in T-cell recruitment to non-lymphoid tissues and sites of inflammation. Nat Rev Immunol 2004;4:1–11.CrossRefGoogle ScholarPubMed
Hey, NA, Graham, RA, Seif, MW, et al. The polymorphic epithelial mucin MUC1 in human endometrium is regulated with maximal expression in the implantation phase. J Clin Endocrinol Metab 1994;78:337–42.Google ScholarPubMed
Meseguer, M, Aplin, JD, Caballero-Campo, P, et al. Human endometrial mucin MUC1 is up-regulated by progesterone and down-regulated in vitro by the human blastocyst. Biol Reprod 2001;64:590–601.CrossRefGoogle ScholarPubMed
Vicente-Manzanares, M, Sánchez-Madrid, F. Role of the cytoskeleton during leukocyte responses. Nat Rev Immunol 2004;4: 110–22.CrossRefGoogle ScholarPubMed
Vicente-Manzanares, M, Sancho, D, Yáñez-Mó, M, et al. The leukocyte cytoskeleton in cell migration and immune interactions. Int Rev Cytol 2002;216:233–89.CrossRefGoogle ScholarPubMed
Sanchez-Madrid, F, del Pozo, MA. Leukocyte polarization in cell migration and immune interactions. EMBO J 1999;18:501–11.CrossRefGoogle ScholarPubMed
Aplin, JD. Adhesion molecules in implantation. Rev Reprod 1997;2:84–93.CrossRefGoogle ScholarPubMed
Lessey, BA, Yeh, Castelbaum AJ, et al. Endometrial progesterone receptors and markers of uterine receptivity in the window of implantation. Fertil Steril 1996;65:477–83.CrossRefGoogle ScholarPubMed
Simón, C, Gimeno, MJ, Mercader, A, et al. Cytokines-adhesion molecules-invasive proteinases. The missing paracrine/autocrine link in embryonic implantation?Mol Hum Reprod 1996;2:405–24.CrossRefGoogle ScholarPubMed
Fássler, R, Meyer, M. Consequences of lack of β1 integrin gene expression in mice. Genes Dev 1995;9:1876–908.CrossRefGoogle ScholarPubMed
Luscinskas, FW, Ma, S, Nusrat, A, et al. The role of endothelial cell lateral junctions during leukocyte trafficking. Immunol Rev 2002; 186:57–67.CrossRefGoogle ScholarPubMed
Vestweber, D. Regulation of endothelial cell contacts during leukocyte extravasation. Curr Opin Cell Biol 2002;14:587–93.CrossRefGoogle ScholarPubMed
Galan, A, Herrer, R, Remohi, J, et al. Embryonic regulation of endometrial epithelial apoptosis during human implantation. Hum Reprod 2000;15 (Suppl. 6):74–80.Google ScholarPubMed
Kamijo, T, Rajabi, MR, Mizunuma, H, et al. Biochemical evidence for autocrine/paracrine regulation of apoptosis in cultured uterine epithelial cells during mouse embryo implantation in vitro. Mol Hum Reprod 1998;4:990–8.CrossRefGoogle ScholarPubMed
Bischof, P, Meisser, A, Campana, A. Control of MMP-9 expression at the maternal-fetal interface. J Reprod Immunol 2002;55:3–10.CrossRefGoogle ScholarPubMed
Schena, M., Shalon, D, Davis, RW, et al. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 1995;270:467–70.CrossRefGoogle ScholarPubMed
Stoughton, RB. Applications of DNA microarrrays in biology. Ann Rev Biochem 2005;74:53–82.CrossRefGoogle Scholar
Mata, J, Marguerat, S, Bahler, J. Post-transcriptional control of gene expression: a genome-wide perspective. Trend Biochem Sci 2005;30:506–14.CrossRefGoogle ScholarPubMed
Giudice, LC. Elucidating endometrial function in the post-genomic era. Hum Reprod Update 2003;9:223–35.CrossRefGoogle ScholarPubMed
Salamonsen, , Nie, G, Findlay, JK. Newly identified endometrial genes of importance for implantation. J Reprod Immunol 2002; 53(1–2):215–25.CrossRefGoogle ScholarPubMed
Kao, LC, Germeyer, A, Tulac, S, et al. Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Endocrinology 2003;144:2870–81.CrossRefGoogle ScholarPubMed
Carson, D, Lagow, E, Thathiah, A, et al. Changes in gene expression during the early to mid-luteal (receptive phase) transition in human endometrium detected by high-density microarray screening. Mol Hum Reprod 2002;8: 971–879.CrossRefGoogle ScholarPubMed
Borthwick, J, Charnock-Jones, S, Tom, B, et al. Determination of the transcript profile of human endometrium. Mol Hum Reprod 2003;9:19–33.CrossRefGoogle ScholarPubMed
Riesewijk, A, Martin, J, Horcajadas, JA, et al. Gene expression profiling of human endometrial receptivity on days LH+2 versus LH+7 by microarray technology. Mol Hum Reprod 2003;9: 253–64.CrossRefGoogle ScholarPubMed
Julkunen, M, Koistenen, R, Sjoberg, J, et al. Secretory endometrium synthesizes placental protein 14. Endocrinology 1986;118:1782–6.CrossRefGoogle ScholarPubMed
Apparao, KB, Murray, MJ, Fritz, MA, et al. Osteopontin and its receptor alpha (v) beta (3) integrin are coexpressed in the human endometrium during the menstrual cycle but regulated differentially. J Clin Endocrinol Metab 2001;86:4991–5000.Google Scholar
Zhou, J, Dsupin, BA, Giudice, L, et al. Insulin-like growth factor system gene expression in human endometrium during the menstrual cycle. J Clin Endocrinol Metab 1994;79:1723–34.Google ScholarPubMed
Catalano, RD, Yanaihara, A, Evans, AL, et al. The effect of RU486 on the gene expression profile in an endometrial explant model. Mol Hum Reprod 2003;9:465–73.CrossRefGoogle Scholar
Horcajadas, JA, Riesewijk, A, Polman, J, et al. Effect of controlled ovarian hyperstimulation in IVF on endometrial gene expression profiles. Mol Human Reprod 2005;11:195–205.CrossRefGoogle ScholarPubMed
Simon, C, Oberye, J, Bellver, J, et al. Similar endometrial development in oocyte donors treated with either high- or standard-dose GnRH antagonist compared to treatment with a GnRH agonist or in natural cycles. Hum Reprod 2005;20(12):3318–27.CrossRefGoogle ScholarPubMed
Parkinson, H, Sarkans, U, Shojatalab, MA, et al. ArrayExpress—a public repository for microarray gene expression data at the EBI. Nucleic Acids Res 2005;33(Database issue):D553–5.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×