Embryo–epithelium interactions during implantation at a glance

ABSTRACT At implantation, with the acquisition of a receptive phenotype in the uterine epithelium, an initial tenuous attachment of embryonic trophectoderm initiates reorganisation of epithelial polarity to enable stable embryo attachment and the differentiation of invasive trophoblasts. In this Cell Science at a Glance article, we describe cellular and molecular events during the epithelial phase of implantation in rodent, drawing on morphological studies both in vivo and in vitro, and genetic models. Evidence is emerging for a repertoire of transcription factors downstream of the master steroidal regulators estrogen and progesterone that coordinate alterations in epithelial polarity, delivery of signals to the stroma and epithelial cell death or displacement. We discuss what is known of the cell interactions that occur during implantation, before considering specific adhesion molecules. We compare the rodent data with our much more limited knowledge of the human system, where direct mechanistic evidence is hard to obtain. In the accompanying poster, we represent the embryo–epithelium interactions in humans and laboratory rodents, highlighting similarities and differences, as well as depict some of the key cell biological events that enable interstitial implantation to occur. Summary: At implantation, attachment of embryonic trophectoderm alters epithelial polarity and invasive trophoblast differentiates. We describe cellular and molecular events during the epithelial phase in rodent and human.

[1]  S. Zhang,et al.  Relocalisation and activation of integrins induced rapidly by oestrogen via G-protein-coupled receptor 30 in mouse blastocysts. , 2016, Reproduction, fertility, and development.

[2]  K. Gemzell‐Danielsson,et al.  Effects of low doses of mifepristone on human embryo implantation process in a three-dimensional human endometrial in vitro co-culture system. , 2016, Contraception.

[3]  I. Larina,et al.  SMAD Signaling Is Required for Structural Integrity of the Female Reproductive Tract and Uterine Function During Early Pregnancy in Mice , 2016, Biology of reproduction.

[4]  A. Brivanlou,et al.  Self-organization of the in vitro attached human embryo , 2016, Nature.

[5]  Dusko Ilic,et al.  Self-organisation of the human embryo in the absence of maternal tissues , 2016, Nature Cell Biology.

[6]  Yoshiakira Kanai,et al.  Mouse Sox17 haploinsufficiency leads to female subfertility due to impaired implantation , 2016, Scientific Reports.

[7]  S. Dey,et al.  Uterine inactivation of muscle segment homeobox (Msx) genes alters epithelial cell junction proteins during embryo implantation , 2016, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  C. Creighton,et al.  Uterine ALK3 is essential during the window of implantation , 2015, Proceedings of the National Academy of Sciences.

[9]  W. Yeung,et al.  Establishment of a novel human embryonic stem cell-derived trophoblastic spheroid implantation model. , 2015, Human reproduction.

[10]  S. Martínez,et al.  Hsa-miR-30d, secreted by the human endometrium, is taken up by the pre-implantation embryo and might modify its transcriptome , 2015, Development.

[11]  F. DeMayo,et al.  Uterine RAC1 via Pak1-ERM signaling directs normal luminal epithelial integrity conducive to on-time embryo implantation in mice , 2015, Cell Death and Differentiation.

[12]  D. Stainier,et al.  Genetic compensation induced by deleterious mutations but not gene knockdowns , 2015, Nature.

[13]  B. Vollenhoven,et al.  Posttranslational removal of α‐dystroglycan N terminus by PC5/6 cleavage is important for uterine preparation for embryo implantation in women , 2015, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[14]  A. Manninen Epithelial polarity--generating and integrating signals from the ECM with integrins. , 2015, Experimental cell research.

[15]  S. Dey,et al.  Entosis Allows Timely Elimination of the Luminal Epithelial Barrier for Embryo Implantation , 2015, Cell reports.

[16]  R. Jha,et al.  Integrin Beta 8 (ITGB8) Regulates Embryo Implantation Potentially via Controlling the Activity of TGF-B1 in Mice1 , 2015, Biology of reproduction.

[17]  C. Jones,et al.  Tracking nutrient transfer at the human maternofetal interface from 4 weeks to term. , 2015, Placenta.

[18]  S. Kimber,et al.  miR-145 suppresses embryo–epithelial juxtacrine communication at implantation by modulating maternal IGF1R , 2015, Journal of Cell Science.

[19]  F. Bazer,et al.  Osteopontin: a leading candidate adhesion molecule for implantation in pigs and sheep , 2014, Journal of Animal Science and Biotechnology.

[20]  V. Goossens,et al.  Assisted reproductive technology in Europe, 2010: results generated from European registers by ESHRE†. , 2014, Human reproduction.

[21]  S. Dey,et al.  Cadence of procreation: orchestrating embryo-uterine interactions. , 2014, Seminars in cell & developmental biology.

[22]  J. Brosens,et al.  The Human Endometrium as a Sensor of Embryo Quality1 , 2014, Biology of reproduction.

[23]  C. Stewart,et al.  The LIF-Mediated Molecular Signature Regulating Murine Embryo Implantation1 , 2014, Biology of reproduction.

[24]  J. Brosens,et al.  Cyclic decidualization of the human endometrium in reproductive health and failure. , 2014, Endocrine reviews.

[25]  S. Young,et al.  Expression of the transmembrane mucins, MUC1, MUC4 and MUC16, in normal endometrium and in endometriosis. , 2014, Human reproduction.

[26]  Terry P Yamaguchi,et al.  Appropriate crypt formation in the uterus for embryo homing and implantation requires Wnt5a-ROR signaling. , 2014, Cell reports.

[27]  F. DeMayo,et al.  Progesterone receptor signaling in the initiation of pregnancy and preservation of a healthy uterus. , 2014, The International journal of developmental biology.

[28]  D. Blesa,et al.  Transcriptomics of the human endometrium. , 2014, The International journal of developmental biology.

[29]  J. Aplin,et al.  The role of the osteopontin-integrin αvβ3 interaction at implantation: functional analysis using three different in vitro models. , 2014, Human reproduction.

[30]  S. Oehninger,et al.  Role for the endometrial epithelial protein MFG-E8 and its receptor integrin αvβ3 in human implantation: results of an in vitro trophoblast attachment study using established human cell lines. , 2014, Fertility and sterility.

[31]  Y. Sung,et al.  KIAA1114, a full-length protein encoded by the trophinin gene, is a novel surface marker for isolating tumor-initiating cells of multiple hepatocellular carcinoma subtypes , 2014, Oncotarget.

[32]  F. Holstege,et al.  Uterine Selection of Human Embryos at Implantation , 2014, Scientific Reports.

[33]  F. DeMayo,et al.  Role of nuclear receptors in blastocyst implantation. , 2013, Seminars in cell & developmental biology.

[34]  R. Behringer,et al.  STAT3 regulates uterine epithelial remodeling and epithelial-stromal crosstalk during implantation. , 2013, Molecular endocrinology.

[35]  P. Chiu,et al.  Identification of CD147 (basigin) as a mediator of trophoblast functions. , 2013, Human reproduction.

[36]  N. Macklon,et al.  In-vitro model systems for the study of human embryo-endometrium interactions. , 2013, Reproductive biomedicine online.

[37]  D. Armant,et al.  Physiological and molecular determinants of embryo implantation. , 2013, Molecular aspects of medicine.

[38]  N. Nicola,et al.  Polyethylene glycated leukemia inhibitory factor antagonist inhibits human blastocyst implantation and triggers apoptosis by down-regulating embryonic AKT. , 2013, Fertility and sterility.

[39]  M. Wallingford,et al.  Morphogenetic analysis of peri‐implantation development , 2013, Developmental dynamics : an official publication of the American Association of Anatomists.

[40]  Nenghui Liu,et al.  The involvement of osteopontin and β3 integrin in implantation and endometrial receptivity in an early mouse pregnancy model. , 2013, European journal of obstetrics, gynecology, and reproductive biology.

[41]  C. Murphy,et al.  Extracellular matrix proteins secreted from both the endometrium and the embryo are required for attachment: A study using a co‐culture model of rat blastocysts and Ishikawa cells , 2013, Journal of morphology.

[42]  Y. Takada,et al.  Insulin-like Growth Factor (IGF) Signaling Requires αvβ3-IGF1-IGF Type 1 Receptor (IGF1R) Ternary Complex Formation in Anchorage Independence, and the Complex Formation Does Not Require IGF1R and Src Activation , 2012, The Journal of Biological Chemistry.

[43]  S. Dey,et al.  Mechanisms of implantation: strategies for successful pregnancy , 2012, Nature Medicine.

[44]  T. Sakurai,et al.  Estrogen-Dependent Uterine Secretion of Osteopontin Activates Blastocyst Adhesion Competence , 2012, PloS one.

[45]  Xin-Mei Liu,et al.  Activation of the epithelial Na+ channel triggers prostaglandin E2 release and production required for embryo implantation , 2012, Nature Medicine.

[46]  Y. Akimoto,et al.  Subcellular localization of L-selectin ligand in the endometrium implies a novel function for pinopodes in endometrial receptivity , 2012, Reproductive Biology and Endocrinology.

[47]  F. DeMayo,et al.  Cdh1 Is Essential for Endometrial Differentiation, Gland Development, and Adult Function in the Mouse Uterus1 , 2012, Biology of reproduction.

[48]  Xuesong Yang,et al.  Differential expression of LeY and fucosyltransferase IV correlates with the receptivity of RL95‐2 and HEC‐1A human uterine epithelial cells , 2012, Cell biology international.

[49]  J. Aplin,et al.  Fucose, placental evolution and the glycocode. , 2012, Glycobiology.

[50]  S. Dey,et al.  Kruppel-like factor 5 (KLF5) is critical for conferring uterine receptivity to implantation , 2012, Proceedings of the National Academy of Sciences.

[51]  S. Dey,et al.  Conditional deletion of Msx homeobox genes in the uterus inhibits blastocyst implantation by altering uterine receptivity. , 2011, Developmental cell.

[52]  J. Brosens,et al.  Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure , 2011, Nature Medicine.

[53]  Y. Li,et al.  Proprotein convertase 5/6 is critical for embryo implantation in women: regulating receptivity by cleaving EBP50, modulating ezrin binding, and membrane-cytoskeletal interactions. , 2011, Endocrinology.

[54]  M. Eijkemans,et al.  Recurrent pre-clinical pregnancy loss is unlikely to be a 'cause' of unexplained infertility. , 2011, Human reproduction.

[55]  J. Deng,et al.  Postnatal Deletion of Wnt7a Inhibits Uterine Gland Morphogenesis and Compromises Adult Fertility in Mice1 , 2011, Biology of reproduction.

[56]  C. Murphy,et al.  Integrin β3 in rat blastocysts and epithelial cells is essential for implantation in vitro: studies with Ishikawa cells and small interfering RNA transfection. , 2011, Human reproduction.

[57]  K. Sugihara,et al.  Trophinin-mediated cell adhesion induces apoptosis of human endometrial epithelial cells through PKC-δ , 2011, Cell cycle.

[58]  K. Korach,et al.  Uterine epithelial estrogen receptor α is dispensable for proliferation but essential for complete biological and biochemical responses , 2010, Proceedings of the National Academy of Sciences.

[59]  S. Martínez,et al.  Human Endometrial CD98 Is Essential for Blastocyst Adhesion , 2010, PloS one.

[60]  G. Burton,et al.  First trimester histiotrophe shows altered sialylation compared with secretory phase glycoconjugates in human endometrium. , 2010, Placenta.

[61]  J. Aplin,et al.  Early stages of implantation as revealed by an in vitro model. , 2010, Reproduction.

[62]  L. Salamonsen,et al.  Models for Study of Human Embryo Implantation: Choice of Cell Lines?1 , 2010, Biology of reproduction.

[63]  D. Carson,et al.  MUC1 is a substrate for γ‐secretase , 2009, Journal of cellular biochemistry.

[64]  Wei Zhang,et al.  Interactions between galectin-3 and integrinbeta3 in regulating endometrial cell proliferation and adhesion. , 2009, Human reproduction.

[65]  Guoyao Wu,et al.  Comparative aspects of implantation. , 2009, Reproduction.

[66]  Harmeet Singh,et al.  Adhesion molecules in endometrial epithelium: tissue integrity and embryo implantation , 2009, Journal of anatomy.

[67]  J. Aplin,et al.  Glycosylation at the fetomaternal interface: does the glycocode play a critical role in implantation? , 2009, Glycoconjugate Journal.

[68]  Zhongshan Wang,et al.  Overexpression of fucosyltransferase VII (FUT7) promotes embryo adhesion and implantation. , 2009, Fertility and sterility.

[69]  S. Dey,et al.  HB-EGF: a unique mediator of embryo-uterine interactions during implantation. , 2009, Experimental cell research.

[70]  R. Casper,et al.  Pinopodes: a questionable role in endometrial receptivity. , 2008, Human reproduction update.

[71]  J. Nakayama,et al.  Trophinin: What embryo implantation teaches us about human cancer. , 2008, Cancer biology & therapy.

[72]  K. Sugihara,et al.  An integrated view of L‐selectin and trophinin function in human embryo implantation , 2008, The journal of obstetrics and gynaecology research.

[73]  V. Goossens,et al.  Assisted reproductive technology in Europe, 2004: results generated from European registers by ESHRE. , 2008, Human reproduction.

[74]  Jennifer L. Farmer,et al.  Galectin 15 (LGALS15): A Gene Uniquely Expressed in the Uteri of Sheep and Goats that Functions in Trophoblast Attachment1 , 2007, Biology of reproduction.

[75]  E. Mekada,et al.  Maternal heparin-binding-EGF deficiency limits pregnancy success in mice , 2007, Proceedings of the National Academy of Sciences.

[76]  T. Mustelin,et al.  Trophoblast cell activation by trophinin ligation is implicated in human embryo implantation , 2007, Proceedings of the National Academy of Sciences.

[77]  Jun Wang,et al.  Trophoblast adhesion of the peri-implantation mouse blastocyst is regulated by integrin signaling that targets phospholipase C. , 2007, Developmental biology.

[78]  Yuji Shimomura,et al.  Possible involvement of crosstalk cell-adhesion mechanism by endometrial CD26/dipeptidyl peptidase IV and embryonal fibronectin in human blastocyst implantation. , 2006, Molecular human reproduction.

[79]  W. Zimmermann,et al.  Mouse pregnancy-specific glycoproteins: tissue-specific expression and evidence of association with maternal vasculature. , 2006, Reproduction.

[80]  Sudhansu K. Dey,et al.  Roadmap to embryo implantation: clues from mouse models , 2006, Nature Reviews Genetics.

[81]  Y. Cao,et al.  Tetraspanin CD9 regulates invasion during mouse embryo implantation. , 2006, Journal of molecular endocrinology.

[82]  K. Handa,et al.  A Specific Microdomain (“Glycosynapse 3”) Controls Phenotypic Conversion and Reversion of Bladder Cancer Cells through GM3-mediated Interaction of α3β1 Integrin with CD9* , 2005, Journal of Biological Chemistry.

[83]  S. Kimber,et al.  Characterization of the uterine phenotype during the peri-implantation period for LIF-null, MF1 strain mice. , 2005, Developmental biology.

[84]  A. Thathiah,et al.  MT1-MMP mediates MUC1 shedding independent of TACE/ADAM17. , 2004, The Biochemical journal.

[85]  C. Murphy Uterine receptivity and the plasma membrane transformation , 2004, Cell Research.

[86]  Jeff Reese,et al.  Molecular cues to implantation. , 2004, Endocrine reviews.

[87]  L. Salamonsen,et al.  Endometrial calbindins are critical for embryo implantation: evidence from in vivo use of morpholino antisense oligonucleotides. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[88]  K. Ohama,et al.  Identification and characterization of extracellular matrix metalloproteinase inducer in human endometrium during the menstrual cycle in vivo and in vitro. , 2003, The Journal of clinical endocrinology and metabolism.

[89]  M. Illera,et al.  A role for alphavbeta3 integrin during implantation in the rabbit model. , 2003, Biology of reproduction.

[90]  M. Illera,et al.  A Role for αvβ3 Integrin During Implantation in the Rabbit Model1 , 2003 .

[91]  Susan J Fisher,et al.  Trophoblast L-Selectin-Mediated Adhesion at the Maternal-Fetal Interface , 2003, Science.

[92]  Jun Wang,et al.  Integrin-Mediated Adhesion and Signaling during Blastocyst Implantation , 2002, Cells Tissues Organs.

[93]  Jun Wang,et al.  Calcitonin Down-regulates E-cadherin Expression in Rodent Uterine Epithelium during Implantation* , 2002, The Journal of Biological Chemistry.

[94]  Hong Chang,et al.  Basigin expression and hormonal regulation in mouse uterus during the peri‐implantation period , 2002, Molecular reproduction and development.

[95]  S. Quenby,et al.  Recurrent miscarriage: a defect in nature's quality control? , 2002, Human reproduction.

[96]  C. Murphy,et al.  The Cytoskeleton of Uterine Epithelial and Stromal Cells , 2002 .

[97]  Peter Lubahn The Fine Structure of the Mature Human Endometrium , 2002 .

[98]  U. Bentin-Ley,et al.  “Pinopodes” and Implantation , 2002, Reviews in Endocrine and Metabolic Disorders.

[99]  N. Copeland,et al.  Significant Differences Between Mouse and Human Trophinins Are Revealed by Their Expression Patterns and Targeted Disruption of Mouse Trophinin Gene1 , 2002, Biology of reproduction.

[100]  A. Aszódi,et al.  Functional consequences of integrin gene mutations in mice. , 2001, Circulation research.

[101]  S. Kimber,et al.  Glycosylation changes during differentiation of the murine uterine epithelium , 2001 .

[102]  M. Meseguer,et al.  MUC1, glycans and the cell-surface barrier to embryo implantation. , 2001, Biochemical Society transactions.

[103]  Marcos Meseguer,et al.  Human Endometrial Mucin MUC1 Is Up-Regulated by Progesterone and Down-Regulated In Vitro by the Human Blastocyst1 , 2001, Biology of reproduction.

[104]  M. Meseguer,et al.  Increased Adhesiveness in Cultured Endometrial-Derived Cells Is Related to the Absence of Moesin Expression1 , 2000, Biology of reproduction.

[105]  M. Illera,et al.  Blockade of the αvβ3 Integrin Adversely Affects Implantation in the Mouse1 , 2000 .

[106]  S K Das,et al.  Zonula occludens-1 and E-cadherin are coordinately expressed in the mouse uterus with the initiation of implantation and decidualization. , 1999, Developmental biology.

[107]  S. Mizutani,et al.  Female sterility in mice lacking the basigin gene, which encodes a transmembrane glycoprotein belonging to the immunoglobulin superfamily , 1998, FEBS letters.

[108]  Y. Cao,et al.  Effects of monoclonal antibody directed to LeY on implantation in the mouse. , 1998, Molecular human reproduction.

[109]  K. Yamamura,et al.  A null mutation in basigin, an immunoglobulin superfamily member, indicates its important roles in peri-implantation development and spermatogenesis. , 1998, Developmental biology.

[110]  K. Daniels,et al.  Dystroglycan is essential for early embryonic development: disruption of Reichert's membrane in Dag1-null mice. , 1997, Human molecular genetics.

[111]  S. Potter,et al.  Abnormal uterine stromal and glandular function associated with maternal reproductive defects in Hoxa-11 null mice. , 1997, Biology of reproduction.

[112]  S. Butz,et al.  Adhesiveness of the apical surface of uterine epithelial cells: the role of junctional complex integrity. , 1996, European journal of cell biology.

[113]  D. Armant,et al.  Molecular interactions between fibronectin and integrins during mouse blastocyst outgrowth , 1995, Molecular reproduction and development.

[114]  R. Pedersen,et al.  Deletion of beta 1 integrins in mice results in inner cell mass failure and peri-implantation lethality. , 1995, Genes & development.

[115]  U. Puistola,et al.  Extracellular matrix interactions in early human embryos: implications for normal implantation events. , 1995, Fertility and sterility.

[116]  M. Seif,et al.  Cell adhesion molecules on the oocyte and preimplantation human embryo. , 1995, Human reproduction.

[117]  D. Armant,et al.  Beta 1- and beta 3-class integrins mediate fibronectin binding activity at the surface of developing mouse peri-implantation blastocysts. Regulation by ligand-induced mobilization of stored receptor , 1995, The Journal of Biological Chemistry.

[118]  Schultz Jf,et al.  Beta 1- and beta 3-class integrins mediate fibronectin binding activity at the surface of developing mouse peri-implantation blastocysts. Regulation by ligand-induced mobilization of stored receptor , 1995 .

[119]  S. Hakomori,et al.  Monoclonal antibody directed to Le(y) oligosaccharide inhibits implantation in the mouse. , 1995, Biology of reproduction.

[120]  T. Horn,et al.  Isolation and culture of human endometrial cells in a three-dimensional culture system. , 1994, Journal of reproduction and fertility.

[121]  C. Damsky,et al.  Developmental regulation of integrin expression at the time of implantation in the mouse embryo. , 1993, Development.

[122]  H. Denker Implantation: a cell biological paradox. , 1993, The Journal of experimental zoology.

[123]  C. Stewart,et al.  Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor , 1992, Nature.

[124]  C. Murphy,et al.  Changes in the apical microfilaments of rat uterine epithelial cells in response to estradiol and progesterone , 1992, The Anatomical record.

[125]  A. Enders,et al.  Chorioallantoic placenta formation in the rat: II. Angiogenesis and maternal blood circulation in the mesometrial region of the implantation chamber prior to placenta formation. , 1991, The American journal of anatomy.

[126]  A. Enders,et al.  Chorioallantoic placenta formation in the rat: I. Luminal epithelial cell death and extracellular matrix modifications in the mesometrial region of implantation chambers. , 1991, The American journal of anatomy.

[127]  D. Martel,et al.  Hormonal dependence of pinopode formation at the uterine luminal surface. , 1991, Human reproduction.

[128]  S. Kimber,et al.  The milk oligosaccharide, lacto-N-fucopentaose I, inhibits attachment of mouse blastocysts on endometrial monolayers. , 1988, Journal of reproduction and fertility.

[129]  C. Damsky,et al.  Expression and function of cell surface extracellular matrix receptors in mouse blastocyst attachment and outgrowth , 1988, The Journal of cell biology.

[130]  A. Enders,et al.  Cellular basis of interaction between trophoblast and uterus at implantation. , 1975, Biology of reproduction.

[131]  Potts Dm The ultrastructure of implantation in the mouse. , 1968 .

[132]  J. Rock,et al.  A description of 34 human ova within the first 17 days of development. , 1956, The American journal of anatomy.

[133]  J. Aplin,et al.  Endometrial apical glycoproteomic analysis reveals roles for cadherin 6, desmoglein-2 and plexin b2 in epithelial integrity. , 2015, Molecular human reproduction.

[134]  Wei Zhang,et al.  Expression of galectin-3 in mouse endometrium and its effect during embryo implantation. , 2012, Reproductive biomedicine online.

[135]  K. Sugihara,et al.  Trophinin in cell adhesion and signal transduction. , 2012, Frontiers in bioscience.

[136]  I. Gipson,et al.  MUC16 Is Lost from the Uterodome (Pinopode) Surface of the Receptive Human Endometrium: In Vitro Evidence That MUC16 Is a Barrier to Trophoblast Adherence1 , 2008, Biology of reproduction.

[137]  J. Aplin Embryo implantation: the molecular mechanism remains elusive. , 2006, Reproductive biomedicine online.

[138]  ChristopherRMURPHY Uterine receptivity and the plasma membrane transformation , 2004 .

[139]  E. Winterhager,et al.  Reproductive Biology and Endocrinology Open Access Apoptosis in Uterine Epithelium and Decidua in Response to Implantation: Evidence for Two Different Pathways , 2003 .

[140]  C. Blobel,et al.  Tumor Necrosis Factor- Converting Enzyme/ADAM 17 Mediates MUC1 Shedding* , 2003 .

[141]  S. Kimber,et al.  Glycosylation changes during differentiation of the murine uterine epithelium. , 2001, Biochemical Society transactions.

[142]  M. Illera,et al.  Blockade of the alpha(v)beta(3) integrin adversely affects implantation in the mouse. , 2000, Biology of reproduction.

[143]  B. Paria,et al.  Coordination of differential effects of primary estrogen and catecholestrogen on two distinct targets mediates embryo implantation in the mouse. , 1998, Endocrinology.

[144]  D. Armant,et al.  Integrin trafficking regulates adhesion to fibronectin during differentiation of mouse peri-implantation blastocysts. , 1997, Developmental genetics.

[145]  Harland W. Mossman Vertebrate fetal membranes , 1987 .

[146]  C. Finn The Implantation Reaction , 1977 .

[147]  D. M. Potts The ultrastructure of implantation in the mouse. , 1968, Journal of anatomy.

[148]  S. Kimber,et al.  Reproductive Biology and Endocrinology Open Access Trophoblast-uterine Interactions at Implantation Milestones of Implantation , 2022 .