Download PDF
Semin Reprod Med 2009; 27(1): 062-079
DOI: 10.1055/s-0028-1108011
© Thieme Medical Publishers

The Role of Growth Factors and Cytokines during Implantation: Endocrine and Paracrine Interactions

Ozlem Guzeloglu-Kayisli1 , Umit Ali Kayisli1 , Hugh S. Taylor1
  • 1Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut
Further Information

Publication History

Publication Date:
05 February 2009 (online)

    Permissions and Reprints

ABSTRACT

Implantation, a critical step for establishing pregnancy, requires molecular and cellular events resulting in uterine growth and differentiation, blastocyst adhesion, invasion, and placental formation. Successful implantation requires a receptive endometrium, a normal and functional embryo at the blastocyst stage, and a synchronized dialogue between maternal and embryonic tissues. In addition to the well-characterized role of sex steroids, the complexity of embryo implantation and placentation is exemplified by the number of cytokines and growth factors with demonstrated roles in these processes. Disturbances in the normal expression and action of these cytokines result in an absolute or partial failure of implantation and abnormal placental formation in mice and human. Members of the gp130 cytokine family, interleukin-11 (IL-11) and leukemia inhibitory factor, the transforming growth factor beta superfamily, the colony-stimulating factors, and the IL-1 and IL-15 systems are crucial molecules for a successful implantation. Chemokines are also important, both in recruiting specific cohorts of leukocytes to the implantation site and in trophoblast trafficking and differentiation. This review provides discussion of the embryonic and uterine factors that are involved in the process of implantation in autocrine, paracrine, and/or juxtacrine manners at the hormonal, cellular, and molecular levels.

KEYWORDS

Blastocyst - endometrium - implantation - pregnancy - uterine biology

REFERENCES

  • 1 Tazuke S I, Giudice L C. Growth factors and cytokines in endometrium, embryonic development, and maternal:embryonic interactions.  Semin Reprod Endocrinol. 1996;  14 231-245
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Carson D D, Bagchi I, Dey S K et al.. Embryo implantation.  Dev Biol. 2000;  223 217-237
    CrossrefPubMedGoogle Scholar
  • 3 Ogita H, Takai Y. Cross-talk among integrin, cadherin, and growth factor receptor: roles of nectin and nectin-like molecule.  Int Rev Cytol. 2008;  265 1-54
    PubMedGoogle Scholar
  • 4 O'Hayre M, Salanga C L, Handel T M, Allen S J. Chemokines and cancer: migration, intracellular signalling and intercellular communication in the microenvironment.  Biochem J. 2008;  409 635-649
    CrossrefPubMedGoogle Scholar
  • 5 Dey S K, Lim H, Das S K et al.. Molecular cues to implantation.  Endocr Rev. 2004;  25 341-373
    CrossrefPubMedGoogle Scholar
  • 6 Makrigiannakis A, Minas V, Kalantaridou S N, Nikas G, Chrousos G P. Hormonal and cytokine regulation of early implantation.  Trends Endocrinol Metab. 2006;  17 178-185
    CrossrefPubMedGoogle Scholar
  • 7 Metcalf D. Hematopoietic cytokines.  Blood. 2008;  111 485-491
    CrossrefPubMedGoogle Scholar
  • 8 Whitman M, Melton D A. Growth factors in early embryogenesis.  Annu Rev Cell Biol. 1989;  5 93-117
    CrossrefPubMedGoogle Scholar
  • 9 Duc-Goiran P, Mignot T M, Bourgeois C, Ferre F. Embryo-maternal interactions at the implantation site: a delicate equilibrium.  Eur J Obstet Gynecol Reprod Biol. 1999;  83 85-100
    PubMedGoogle Scholar
  • 10 Makrigiannakis A, Minas V. Mechanisms of implantation.  Reprod Biomed Online. 2007;  14 102-109
    PubMedGoogle Scholar
  • 11 Red-Horse K, Zhou Y, Genbacev O et al.. Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface.  J Clin Invest. 2004;  114 744-754
    CrossrefPubMedGoogle Scholar
  • 12 Wilcox A J, Weinberg C R, O'Connor J F et al.. Incidence of early loss of pregnancy.  N Engl J Med. 1988;  319 189-194
    CrossrefPubMedGoogle Scholar
  • 13 Norwitz E R, Schust D J, Fisher S J. Implantation and the survival of early pregnancy.  N Engl J Med. 2001;  345 1400-1408
    CrossrefPubMedGoogle Scholar
  • 14 Simon C, Caballero-Campo P, Garcia-Velasco J A, Pellicer A. Potential implications of chemokines in reproductive function: an attractive idea.  J Reprod Immunol. 1998;  38 169-193
    PubMedGoogle Scholar
  • 15 Taylor E, Gomel V. The uterus and fertility.  Fertil Steril. 2008;  89 1-16
    CrossrefPubMedGoogle Scholar
  • 16 Braude P, Bolton V, Moore S. Human gene expression first occurs between the four- and eight-cell stages of preimplantation development.  Nature. 1988;  332 459-461
    CrossrefPubMedGoogle Scholar
  • 17 Flach G, Johnson M H, Braude P R, Taylor R A, Bolton V N. The transition from maternal to embryonic control in the 2-cell mouse embryo.  EMBO J. 1982;  1 681-686
    PubMedGoogle Scholar
  • 18 Richter J D. Cytoplasmic polyadenylation in development and beyond.  Microbiol Mol Biol Rev. 1999;  63 446-456
    PubMedGoogle Scholar
  • 19 Yamanaka Y, Ralston A, Stephenson R O, Rossant J. Cell and molecular regulation of the mouse blastocyst.  Dev Dyn. 2006;  235 2301-2314
    CrossrefPubMedGoogle Scholar
  • 20 Kodaman P H, Taylor H S. Hormonal regulation of implantation.  Obstet Gynecol Clin North Am. 2004;  31 745-766
    CrossrefPubMedGoogle Scholar
  • 21 Lunghi L, Ferretti M E, Medici S, Biondi C, Vesce F. Control of human trophoblast function.  Reprod Biol Endocrinol. 2007;  5 6
    CrossrefPubMedGoogle Scholar
  • 22 Johnson M H, McConnell J M. Lineage allocation and cell polarity during mouse embryogenesis.  Semin Cell Dev Biol. 2004;  15 583-597
    CrossrefPubMedGoogle Scholar
  • 23 Takaoka K, Yamamoto M, Shiratori H et al.. The mouse embryo autonomously acquires anterior-posterior polarity at implantation.  Dev Cell. 2006;  10 451-459
    CrossrefPubMedGoogle Scholar
  • 24 Tabin C J. The key to left-right asymmetry.  Cell. 2006;  127 27-32
    CrossrefPubMedGoogle Scholar
  • 25 Tabibzadeh S, Shea W, Lessey B A, Broome J. From endometrial receptivity to infertility.  Semin Reprod Endocrinol. 1999;  17 197-203
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Simmons D G, Cross J C. Determinants of trophoblast lineage and cell subtype specification in the mouse placenta.  Dev Biol. 2005;  284 12-24
    CrossrefPubMedGoogle Scholar
  • 27 Strowitzki T, Germeyer A, Popovici R, von Wolff M. The human endometrium as a fertility-determining factor.  Hum Reprod Update. 2006;  12 617-630
    PubMedGoogle Scholar
  • 28 Kayisli U A, Guzeloglu-Kayisli O, Arici A. Endocrine-immune interactions in human endometrium.  Ann N Y Acad Sci. 2004;  1034 50-63
    CrossrefPubMedGoogle Scholar
  • 29 Aplin J D. Embryo implantation: the molecular mechanism remains elusive.  Reprod Biomed Online. 2006;  13 833-839
    CrossrefPubMedGoogle Scholar
  • 30 Armant D R, Wang J, Liu Z. Intracellular signaling in the developing blastocyst as a consequence of the maternal-embryonic dialogue.  Semin Reprod Med. 2000;  18 273-287
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Tabibzadeh S, Babaknia A. The signals and molecular pathways involved in implantation, a symbiotic interaction between blastocyst and endometrium involving adhesion and tissue invasion.  Hum Reprod. 1995;  10 1579-1602
    CrossrefPubMedGoogle Scholar
  • 32 Sharkey A M, Smith S K. The endometrium as a cause of implantation failure.  Best Pract Res Clin Obstet Gynaecol. 2003;  17 289-307
    CrossrefPubMedGoogle Scholar
  • 33 Nikas G. Endometrial receptivity: changes in cell-surface morphology.  Semin Reprod Med. 2000;  18 229-235
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Kao L C, Tulac S, Lobo S et al.. Global gene profiling in human endometrium during the window of implantation.  Endocrinology. 2002;  143 2119-2138
    CrossrefPubMedGoogle Scholar
  • 35 Sherwin J R, Sharkey A M, Cameo P et al.. Identification of novel genes regulated by chorionic gonadotropin in baboon endometrium during the window of implantation.  Endocrinology. 2007;  148 618-626
    PubMedGoogle Scholar
  • 36 Enders A C. Trophoblast-uterine interactions in the first days of implantation: models for the study of implantation events in the human.  Semin Reprod Med. 2000;  18 255-263
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 Lessey B A, Palomino W A, Apparao K B, Young S L, Lininger R A. Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women.  Reprod Biol Endocrinol. 2006;  4(suppl 1) S9
    CrossrefPubMedGoogle Scholar
  • 38 Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation.  Hum Reprod Update. 2006;  12 731-746
    CrossrefPubMedGoogle Scholar
  • 39 Huet-Hudson Y M, Dey S K. Requirement for progesterone priming and its long-term effects on implantation in the mouse.  Proc Soc Exp Biol Med. 1990;  193 259-263
    PubMedGoogle Scholar
  • 40 Carpenter K D, Korach K S. Potential biological functions emerging from the different estrogen receptors.  Ann N Y Acad Sci. 2006;  1092 361-373
    CrossrefPubMedGoogle Scholar
  • 41 Hewitt S C, Korach K S. Progesterone action and responses in the alphaERKO mouse.  Steroids. 2000;  65 551-557
    CrossrefPubMedGoogle Scholar
  • 42 Cooke P S, Buchanan D L, Young P et al.. Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium.  Proc Natl Acad Sci U S A. 1997;  94 6535-6540
    CrossrefPubMedGoogle Scholar
  • 43 Curtis S W, Clark J, Myers P, Korach K S. Disruption of estrogen signaling does not prevent progesterone action in the estrogen receptor alpha knockout mouse uterus.  Proc Natl Acad Sci U S A. 1999;  96 3646-3651
    CrossrefPubMedGoogle Scholar
  • 44 Paria B C, Tan J, Lubahn D B, Dey S K, Das S K. Uterine decidual response occurs in estrogen receptor-alpha-deficient mice.  Endocrinology. 1999;  140 2704-2710
    CrossrefPubMedGoogle Scholar
  • 45 Conneely O M, Jericevic B M. Progesterone regulation of reproductive function through functionally distinct progesterone receptor isoforms.  Rev Endocr Metab Disord. 2002;  3 201-209
    CrossrefPubMedGoogle Scholar
  • 46 Nelson K G, Takahashi T, Bossert N L, Walmer D K, McLachlan J A. Epidermal growth factor replaces estrogen in the stimulation of female genital-tract growth and differentiation.  Proc Natl Acad Sci U S A. 1991;  88 21-25
    PubMedGoogle Scholar
  • 47 Ignar-Trowbridge D M, Nelson K G, Bidwell M C et al.. Coupling of dual signaling pathways: epidermal growth factor action involves the estrogen receptor.  Proc Natl Acad Sci U S A. 1992;  89 4658-4662
    CrossrefPubMedGoogle Scholar
  • 48 Johnson D C, Chatterjee S. Epidermal growth factor (EGF) replaces estradiol for the initiation of embryo implantation in the hypophysectomized rat.  Placenta. 1993;  14 429-438
    CrossrefPubMedGoogle Scholar
  • 49 Perrier d'Hauterive S, Berndt S, Tsampalas M et al.. Dialogue between blastocyst hCG and endometrial LH/hCG receptor: which role in implantation?.  Gynecol Obstet Invest. 2007;  64 156-160
    CrossrefPubMedGoogle Scholar
  • 50 Licht P, Russu V, Wildt L. On the role of human chorionic gonadotropin (hCG) in the embryo-endometrial microenvironment: implications for differentiation and implantation.  Semin Reprod Med. 2001;  19 37-47
    Article in Thieme ConnectPubMedGoogle Scholar
  • 51 Zygmunt M, Hahn D, Munstedt K, Bischof P, Lang U. Invasion of cytotrophoblastic JEG-3 cells is stimulated by hCG in vitro.  Placenta. 1998;  19 587-593
    CrossrefPubMedGoogle Scholar
  • 52 Milwidsky A, Finci-Yeheskel Z, Yagel S, Mayer M. Gonadotropin-mediated inhibition of proteolytic enzymes produced by human trophoblast in culture.  J Clin Endocrinol Metab. 1993;  76 1101-1105
    CrossrefPubMedGoogle Scholar
  • 53 Yagel S, Geva T E, Solomon H et al.. High levels of human chorionic gonadotropin retard first trimester trophoblast invasion in vitro by decreasing urokinase plasminogen activator and collagenase activities.  J Clin Endocrinol Metab. 1993;  77 1506-1511
    CrossrefPubMedGoogle Scholar
  • 54 Simón C, Martin J C, Pellicer A. Paracrine regulators of implantation.  Baillieres Best Pract Res Clin Obstet Gynaecol. 2000;  14 815-826
    PubMedGoogle Scholar
  • 55 Laird S M, Tuckerman E M, Li T C. Cytokine expression in the endometrium of women with implantation failure and recurrent miscarriage.  Reprod Biomed Online. 2006;  13 13-23
    PubMedGoogle Scholar
  • 56 Duval D, Reinhardt B, Kedinger C, Boeuf H. Role of suppressors of cytokine signaling (Socs) in leukemia inhibitory factor (LIF)-dependent embryonic stem cell survival.  FASEB J. 2000;  14 1577-1584
    CrossrefPubMedGoogle Scholar
  • 57 Arici A, Engin O, Attar E, Olive D L. Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in human endometrium.  J Clin Endocrinol Metab. 1995;  80 1908-1915
    CrossrefPubMedGoogle Scholar
  • 58 Charnock-Jones D S, Sharkey A M, Fenwick P, Smith S K. Leukaemia inhibitory factor mRNA concentration peaks in human endometrium at the time of implantation and the blastocyst contains mRNA for the receptor at this time.  J Reprod Fertil. 1994;  101 421-426
    CrossrefPubMedGoogle Scholar
  • 59 Aghajanova L, Stavreus-Evers A, Nikas Y, Hovatta O, Landgren B M. Coexpression of pinopodes and leukemia inhibitory factor, as well as its receptor, in human endometrium.  Fertil Steril. 2003;  79(Suppl 1) 808-814
    CrossrefPubMedGoogle Scholar
  • 60 Cullinan E B, Abbondanzo S J, Anderson P S, Pollard J W, Lessey B A, Stewart C L. Leukemia inhibitory factor (LIF) and LIF receptor expression in human endometrium suggests a potential autocrine/paracrine function in regulating embryo implantation.  Proc Natl Acad Sci U S A. 1996;  93 3115-3120
    CrossrefPubMedGoogle Scholar
  • 61 Vogiagis D, Marsh M M, Fry R C, Salamonsen L A. Leukaemia inhibitory factor in human endometrium throughout the menstrual cycle.  J Endocrinol. 1996;  148 95-102
    CrossrefPubMedGoogle Scholar
  • 62 Sharkey A M, King A, Clark D E et al.. Localization of leukemia inhibitory factor and its receptor in human placenta throughout pregnancy.  Biol Reprod. 1999;  60 355-364
    CrossrefPubMedGoogle Scholar
  • 63 Lessey B A, Gui Y, Apparao K B, Young S L, Mulholland J. Regulated expression of heparin-binding EGF-like growth factor (HB-EGF) in the human endometrium: a potential paracrine role during implantation.  Mol Reprod Dev. 2002;  62 446-455
    CrossrefPubMedGoogle Scholar
  • 64 Song H, Lim H, Das S K, Paria B C, Dey S K. Dysregulation of EGF family of growth factors and COX-2 in the uterus during the preattachment and attachment reactions of the blastocyst with the luminal epithelium correlates with implantation failure in LIF-deficient mice.  Mol Endocrinol. 2000;  14 1147-1161
    CrossrefPubMedGoogle Scholar
  • 65 Laird S M, Tuckerman E M, Dalton C F, Dunphy B C, Li T C, Zhang X. The production of leukaemia inhibitory factor by human endometrium: presence in uterine flushings and production by cells in culture.  Hum Reprod. 1997;  12 569-574
    CrossrefPubMedGoogle Scholar
  • 66 Ledee-Bataille N, Lapree-Delage G, Taupin J L, Dubanchet S, Frydman R, Chaouat G. Concentration of leukaemia inhibitory factor (LIF) in uterine flushing fluid is highly predictive of embryo implantation.  Hum Reprod. 2002;  17 213-218
    CrossrefPubMedGoogle Scholar
  • 67 Giess R, Tanasescu I, Steck T, Sendtner M. Leukaemia inhibitory factor gene mutations in infertile women.  Mol Hum Reprod. 1999;  5 581-586
    CrossrefPubMedGoogle Scholar
  • 68 Steck T, Giess R, Suetterlin M W et al.. Leukaemia inhibitory factor (LIF) gene mutations in women with unexplained infertility and recurrent failure of implantation after IVF and embryo transfer.  Eur J Obstet Gynecol Reprod Biol. 2004;  112 69-73
    CrossrefPubMedGoogle Scholar
  • 69 Escary J L, Perreau J, Dumenil D, Ezine S, Brulet P. Leukaemia inhibitory factor is necessary for maintenance of haematopoietic stem cells and thymocyte stimulation.  Nature. 1993;  363 361-364
    CrossrefPubMedGoogle Scholar
  • 70 Stewart C L, Kaspar P, Brunet L J et al.. Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor.  Nature. 1992;  359 76-79
    CrossrefPubMedGoogle Scholar
  • 71 Dunglison G F, Barlow D H, Sargent I L. Leukaemia inhibitory factor significantly enhances the blastocyst formation rates of human embryos cultured in serum-free medium.  Hum Reprod. 1996;  11 191-196
    PubMedGoogle Scholar
  • 72 Nichols J, Davidson D, Taga T, Yoshida K, Chambers I, Smith A. Complementary tissue-specific expression of LIF and LIF-receptor mRNAs in early mouse embryogenesis.  Mech Dev. 1996;  57 123-131
    CrossrefPubMedGoogle Scholar
  • 73 Ware C B, Horowitz M C, Renshaw B R et al.. Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death.  Development. 1995;  121 1283-1299
    PubMedGoogle Scholar
  • 74 Yoshida K, Taga T, Saito M et al.. Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders.  Proc Natl Acad Sci U S A. 1996;  93 407-411
    CrossrefPubMedGoogle Scholar
  • 75 Sharkey A M, Dellow K, Blayney M, Macnamee M, Charnock-Jones S, Smith S K. Stage-specific expression of cytokine and receptor messenger ribonucleic acids in human preimplantation embryos.  Biol Reprod. 1995;  53 974-981
    PubMedGoogle Scholar
  • 76 Sherwin J R, Smith S K, Wilson A, Sharkey A M. Soluble gp130 is up-regulated in the implantation window and shows altered secretion in patients with primary unexplained infertility.  J Clin Endocrinol Metab. 2002;  87 3953-3960
    CrossrefPubMedGoogle Scholar
  • 77 Gearing D P, Thut C J, VandeBos T et al.. Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130.  EMBO J. 1991;  10 2839-2848
    PubMedGoogle Scholar
  • 78 Robertson S A, O'Connell A, Ramsey A. The effect of interleukin-6 deficiency on implantation, fetal development and parturition in mice.  Proc Aust Soc Reprod Biol. 2000;  31 97
    PubMedGoogle Scholar
  • 79 Nasu K, Matsui N, Narahara H, Tanaka Y, Miyakawa I. Effects of interferon-gamma on cytokine production by endometrial stromal cells.  Hum Reprod. 1998;  13 2598-2601
    CrossrefPubMedGoogle Scholar
  • 80 Jauniaux E, Gulbis B, Schandene L, Collette J, Hustin J. Distribution of interleukin-6 in maternal and embryonic tissues during the first trimester.  Mol Hum Reprod. 1996;  2 239-243
    CrossrefPubMedGoogle Scholar
  • 81 Stephanou A, Myatt L, Eis A L, Sarlis N, Jikihara H, Handwerger S. Ontogeny of the expression and regulation of interleukin-6 (IL-6) and IL-1 mRNAs by human trophoblast cells during differentiation in vitro.  J Endocrinol. 1995;  147 487-496
    CrossrefPubMedGoogle Scholar
  • 82 Jasper M J, Tremellen K P, Robertson S A. Reduced expression of IL-6 and IL-1alpha mRNAs in secretory phase endometrium of women with recurrent miscarriage.  J Reprod Immunol. 2007;  73 74-84
    PubMedGoogle Scholar
  • 83 Du X X, Williams D A. Interleukin-11: a multifunctional growth factor derived from the hematopoietic microenvironment.  Blood. 1994;  83 2023-2030
    PubMedGoogle Scholar
  • 84 Sands B E, Bank S, Sninsky C A et al.. Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn's disease.  Gastroenterology. 1999;  117 58-64
    PubMedGoogle Scholar
  • 85 Cork B A, Li T C, Warren M A, Laird S M. Interleukin-11 (IL-11) in human endometrium: expression throughout the menstrual cycle and the effects of cytokines on endometrial IL-11 production in vitro.  J Reprod Immunol. 2001;  50 3-17
    CrossrefPubMedGoogle Scholar
  • 86 Dimitriadis E, Salamonsen L A, Robb L. Expression of interleukin-11 during the human menstrual cycle: coincidence with stromal cell decidualization and relationship to leukaemia inhibitory factor and prolactin.  Mol Hum Reprod. 2000;  6 907-914
    CrossrefPubMedGoogle Scholar
  • 87 von Rango U, Alfer J, Kertschanska S et al.. Interleukin-11 expression: its significance in eutopic and ectopic human implantation.  Mol Hum Reprod. 2004;  10 783-792
    CrossrefPubMedGoogle Scholar
  • 88 Chen H F, Lin C Y, Chao K H, Wu M Y, Yang Y S, Ho H N. Defective production of interleukin-11 by decidua and chorionic villi in human anembryonic pregnancy.  J Clin Endocrinol Metab. 2002;  87 2320-2328
    CrossrefPubMedGoogle Scholar
  • 89 Cork B A, Tuckerman E M, Li T C, Laird S M. Expression of interleukin (IL)-11 receptor by the human endometrium in vivo and effects of IL-11, IL-6 and LIF on the production of MMP and cytokines by human endometrial cells in vitro.  Mol Hum Reprod. 2002;  8 841-848
    CrossrefPubMedGoogle Scholar
  • 90 Dimitriadis E, Robb L, Salamonsen L A. Interleukin 11 advances progesterone-induced decidualization of human endometrial stromal cells.  Mol Hum Reprod. 2002;  8 636-643
    CrossrefPubMedGoogle Scholar
  • 91 Popovici R M, Kao L C, Giudice L C. Discovery of new inducible genes in in vitro decidualized human endometrial stromal cells using microarray technology.  Endocrinology. 2000;  141 3510-3513
    CrossrefPubMedGoogle Scholar
  • 92 Tierney E P, Tulac S, Huang S T, Giudice L C. Activation of the protein kinase A pathway in human endometrial stromal cells reveals sequential categorical gene regulation.  Physiol Genomics. 2003;  16 47-66
    CrossrefPubMedGoogle Scholar
  • 93 Ain R, Trinh M L, Soares M J. Interleukin-11 signaling is required for the differentiation of natural killer cells at the maternal-fetal interface.  Dev Dyn. 2004;  231 700-708
    CrossrefPubMedGoogle Scholar
  • 94 Kang J, Der S D. Cytokine functions in the formative stages of a lymphocyte's life.  Curr Opin Immunol. 2004;  16 180-190
    CrossrefPubMedGoogle Scholar
  • 95 Eriksson M, Meadows S K, Wira C R, Sentman C L. Unique phenotype of human uterine NK cells and their regulation by endogenous TGF-beta.  J Leukoc Biol. 2004;  76 667-675
    CrossrefPubMedGoogle Scholar
  • 96 Verma S, Hiby S E, Loke Y W, King A. Human decidual natural killer cells express the receptor for and respond to the cytokine interleukin 15.  Biol Reprod. 2000;  62 959-968
    CrossrefPubMedGoogle Scholar
  • 97 Kitaya K, Nakayama T, Okubo T, Kuroboshi H, Fushiki S, Honjo H. Expression of macrophage inflammatory protein-1beta in human endometrium: its role in endometrial recruitment of natural killer cells.  J Clin Endocrinol Metab. 2003;  88 1809-1814
    CrossrefPubMedGoogle Scholar
  • 98 Ashkar A A, Black G P, Wei Q et al.. Assessment of requirements for IL-15 and IFN regulatory factors in uterine NK cell differentiation and function during pregnancy.  J Immunol. 2003;  171 2937-2944
    PubMedGoogle Scholar
  • 99 Dunn C L, Critchley H O, Kelly R W. IL-15 regulation in human endometrial stromal cells.  J Clin Endocrinol Metab. 2002;  87 1898-1901
    CrossrefPubMedGoogle Scholar
  • 100 Bankers-Fulbright J L, Kalli K R, McKean D J. Interleukin-1 signal transduction.  Life Sci. 1996;  59 61-83
    CrossrefPubMedGoogle Scholar
  • 101 Svenson M, Hansen M B, Heegaard P, Abell K, Bendtzen K. Specific binding of interleukin 1 (IL-1) beta and IL-1 receptor antagonist (IL-1ra) to human serum. High-affinity binding of IL-1ra to soluble IL-1 receptor type I.  Cytokine. 1993;  5 427-435
    CrossrefPubMedGoogle Scholar
  • 102 Bischof P, Campana A. Molecular mediators of implantation.  Baillieres Best Pract Res Clin Obstet Gynaecol. 2000;  14 801-814
    CrossrefPubMedGoogle Scholar
  • 103 Vigano P, Mangioni S, Pompei F, Chiodo I. Maternal-conceptus cross talk—a review.  Placenta. 2003;  24(Suppl B) S56-S61
    CrossrefPubMedGoogle Scholar
  • 104 Hofmann G E, Scott Jr R T, Bergh P A, Deligdisch L. Immunohistochemical localization of epidermal growth factor in human endometrium, decidua, and placenta.  J Clin Endocrinol Metab. 1991;  73 882-887
    PubMedGoogle Scholar
  • 105 Bass K E, Morrish D, Roth I et al.. Human cytotrophoblast invasion is up-regulated by epidermal growth factor: evidence that paracrine factors modify this process.  Dev Biol. 1994;  164 550-561
    CrossrefPubMedGoogle Scholar
  • 106 Li R H, Zhuang L Z. The effects of growth factors on human normal placental cytotrophoblast cell proliferation.  Hum Reprod. 1997;  12 830-834
    CrossrefPubMedGoogle Scholar
  • 107 Kamei Y, Tsutsumi O, Kuwabara Y, Taketani Y. Intrauterine growth retardation and fetal losses are caused by epidermal growth factor deficiency in mice.  Am J Physiol. 1993;  264 R597-R600
    PubMedGoogle Scholar
  • 108 Tsutsumi O, Oka T. Epidermal growth factor deficiency during pregnancy causes abortion in mice.  Am J Obstet Gynecol. 1987;  156 241-244
    PubMedGoogle Scholar
  • 109 Johnson D C, Banerjee S, Chatterjee S. Estradiol and chlordecone (Kepone) decrease adenosine 3′5'-cyclic monophosphate concentrations in the ovariectomized immature rat uterus.  Proc Soc Exp Biol Med. 1995;  210 33-38
    PubMedGoogle Scholar
  • 110 Threadgill D W, Dlugosz A A, Hansen L A et al.. Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype.  Science. 1995;  269 230-234
    CrossrefPubMedGoogle Scholar
  • 111 De La Fuente R, O'Brien M J, Eppig J J. Epidermal growth factor enhances preimplantation developmental competence of maturing mouse oocytes.  Hum Reprod. 1999;  14 3060-3068
    CrossrefPubMedGoogle Scholar
  • 112 Goldman S, Gonen Y. Monoclonal antibodies against epidermal growth factor prevent outgrowth of mouse embryos in vitro.  Hum Reprod. 1998;  13 2231-2233
    CrossrefPubMedGoogle Scholar
  • 113 Harvey M B, Leco K J, Arcellana-Panlilio M Y, Zhang X, Edwards D R, Schultz G A. Proteinase expression in early mouse embryos is regulated by leukaemia inhibitory factor and epidermal growth factor.  Development. 1995;  121 1005-1014
    PubMedGoogle Scholar
  • 114 Khamsi F, Armstrong D T, Zhang X. Expression of urokinase-type plasminogen activator in human preimplantation embryos.  Mol Hum Reprod. 1996;  2 273-276
    CrossrefPubMedGoogle Scholar
  • 115 Wiley L M, Wu J X, Harari I, Adamson E D. Epidermal growth factor receptor mRNA and protein increase after the four-cell preimplantation stage in murine development.  Dev Biol. 1992;  149 247-260
    CrossrefPubMedGoogle Scholar
  • 116 Lim H, Das S K, Dey S K. erbB genes in the mouse uterus: cell-specific signaling by epidermal growth factor (EGF) family of growth factors during implantation.  Dev Biol. 1998;  204 97-110
    CrossrefPubMedGoogle Scholar
  • 117 Surveyor G A, Gendler S J, Pemberton L et al.. Expression and steroid hormonal control of Muc-1 in the mouse uterus.  Endocrinology. 1995;  136 3639-3647
    CrossrefPubMedGoogle Scholar
  • 118 Das S K, Chakraborty I, Paria B C, Wang X N, Plowman G, Dey S K. Amphiregulin is an implantation-specific and progesterone-regulated gene in the mouse uterus.  Mol Endocrinol. 1995;  9 691-705
    CrossrefPubMedGoogle Scholar
  • 119 Das S K, Das N, Wang J et al.. Expression of betacellulin and epiregulin genes in the mouse uterus temporally by the blastocyst solely at the site of its apposition is coincident with the “window” of implantation.  Dev Biol. 1997;  190 178-190
    CrossrefPubMedGoogle Scholar
  • 120 Leach R E, Khalifa R, Ramirez N D et al.. Multiple roles for heparin-binding epidermal growth factor-like growth factor are suggested by its cell-specific expression during the human endometrial cycle and early placentation.  J Clin Endocrinol Metab. 1999;  84 3355-3363
    CrossrefPubMedGoogle Scholar
  • 121 Yoo H J, Barlow D H, Mardon H J. Temporal and spatial regulation of expression of heparin-binding epidermal growth factor-like growth factor in the human endometrium: a possible role in blastocyst implantation.  Dev Genet. 1997;  21 102-108
    CrossrefPubMedGoogle Scholar
  • 122 Martin K L, Barlow D H, Sargent I L. Heparin-binding epidermal growth factor significantly improves human blastocyst development and hatching in serum-free medium.  Hum Reprod. 1998;  13 1645-1652
    CrossrefPubMedGoogle Scholar
  • 123 Chobotova K, Spyropoulou I, Carver J et al.. Heparin-binding epidermal growth factor and its receptor ErbB4 mediate implantation of the human blastocyst.  Mech Dev. 2002;  119 137-144
    CrossrefPubMedGoogle Scholar
  • 124 Tabibzadeh S, Hemmati-Brivanlou A. Lefty at the crossroads of “stemness” and differentiative events.  Stem Cells. 2006;  24 1998-2006
    CrossrefPubMedGoogle Scholar
  • 125 Feinberg R F, Kliman H J, Wang C L. Transforming growth factor-beta stimulates trophoblast oncofetal fibronectin synthesis in vitro: implications for trophoblast implantation in vivo.  J Clin Endocrinol Metab. 1994;  78 1241-1248
    CrossrefPubMedGoogle Scholar
  • 126 Tamada H, McMaster M T, Flanders K C, Andrews G K, Dey S K. Cell type-specific expression of transforming growth factor-beta 1 in the mouse uterus during the periimplantation period.  Mol Endocrinol. 1990;  4 965-972
    PubMedGoogle Scholar
  • 127 Mazella J, Tang M, Tseng L. Disparate effects of relaxin and TGFbeta1: relaxin increases, but TGFbeta1 inhibits, the relaxin receptor and the production of IGFBP-1 in human endometrial stromal/decidual cells.  Hum Reprod. 2004;  19 1513-1518
    CrossrefPubMedGoogle Scholar
  • 128 Kulkarni A B, Karlsson S. Transforming growth factor-beta 1 knockout mice. A mutation in one cytokine gene causes a dramatic inflammatory disease.  Am J Pathol. 1993;  143 3-9
    PubMedGoogle Scholar
  • 129 Graham C H, Connelly I, MacDougall J R, Kerbel R S, Stetler-Stevenson W G, Lala P K. Resistance of malignant trophoblast cells to both the anti-proliferative and anti-invasive effects of transforming growth factor-beta.  Exp Cell Res. 1994;  214 93-99
    CrossrefPubMedGoogle Scholar
  • 130 Caniggia I, Winter J, Lye S J, Post M. Oxygen and placental development during the first trimester: implications for the pathophysiology of pre-eclampsia.  Placenta. 2000;  21(suppl A) S25-S30
    CrossrefPubMedGoogle Scholar
  • 131 Djurovic S, Schjetlein R, Wisloff F, Haugen G, Husby H, Berg K. Plasma concentrations of Lp(a) lipoprotein and TGF-beta1 are altered in preeclampsia.  Clin Genet. 1997;  52 371-376
    PubMedGoogle Scholar
  • 132 Hamilton G S, Lysiak J J, Han V K, Lala P K. Autocrine-paracrine regulation of human trophoblast invasiveness by insulin-like growth factor (IGF)-II and IGF-binding protein (IGFBP)-1.  Exp Cell Res. 1998;  244 147-156
    CrossrefPubMedGoogle Scholar
  • 133 Irving J A, Lala P K. Functional role of cell surface integrins on human trophoblast cell migration: regulation by TGF-beta, IGF-II, and IGFBP-1.  Exp Cell Res. 1995;  217 419-427
    CrossrefPubMedGoogle Scholar
  • 134 Irwin J C, de las Fuentes L, Dsupin B A, Giudice L C. Insulin-like growth factor regulation of human endometrial stromal cell function: coordinate effects on insulin-like growth factor binding protein-1, cell proliferation and prolactin secretion.  Regul Pept. 1993;  48(1–2) 165-177
    CrossrefPubMedGoogle Scholar
  • 135 Fowler D J, Nicolaides K H, Miell J P. Insulin-like growth factor binding protein-1 (IGFBP-1): a multifunctional role in the human female reproductive tract.  Hum Reprod Update. 2000;  6 495-504
    CrossrefPubMedGoogle Scholar
  • 136 Han V K, Bassett N, Walton J, Challis J R. The expression of insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) genes in the human placenta and membranes: evidence for IGF-IGFBP interactions at the feto-maternal interface.  J Clin Endocrinol Metab. 1996;  81(7) 2680-2693
    CrossrefPubMedGoogle Scholar
  • 137 Makarevich A V, Markkula M. Apoptosis and cell proliferation potential of bovine embryos stimulated with insulin-like growth factor I during in vitro maturation and culture.  Biol Reprod. 2002;  66 386-392
    CrossrefPubMedGoogle Scholar
  • 138 Kolle S, Stojkovic M, Boie G, Wolf E, Sinowatz F. Growth hormone-related effects on apoptosis, mitosis, and expression of connexin 43 in bovine in vitro maturation cumulus-oocyte complexes.  Biol Reprod. 2003;  68 1584-1589
    PubMedGoogle Scholar
  • 139 Spanos S, Becker D L, Winston R M, Hardy K. Anti-apoptotic action of insulin-like growth factor-I during human preimplantation embryo development.  Biol Reprod. 2000;  63 1413-1420
    CrossrefPubMedGoogle Scholar
  • 140 Ferrara N. Vascular endothelial growth factor: basic science and clinical progress.  Endocr Rev. 2004;  25 581-611
    CrossrefPubMedGoogle Scholar
  • 141 Maglione D, Guerriero V, Viglietto G et al.. Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14.  Oncogene. 1993;  8 925-931
    PubMedGoogle Scholar
  • 142 Olofsson B, Korpelainen E, Pepper M S et al.. Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells.  Proc Natl Acad Sci U S A. 1998;  95 11709-11714
    CrossrefPubMedGoogle Scholar
  • 143 Joukov V, Sorsa T, Kumar V et al.. Proteolytic processing regulates receptor specificity and activity of VEGF-C.  EMBO J. 1997;  16 3898-3911
    CrossrefPubMedGoogle Scholar
  • 144 Achen M G, Jeltsch M, Kukk E et al.. Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4).  Proc Natl Acad Sci U S A. 1998;  95 548-553
    CrossrefPubMedGoogle Scholar
  • 145 Cunningham S A, Tran T M, Arrate M P, Brock T A. Characterization of vascular endothelial cell growth factor interactions with the kinase insert domain-containing receptor tyrosine kinase. A real time kinetic study.  J Biol Chem. 1999;  274 18421-18427
    CrossrefPubMedGoogle Scholar
  • 146 Park J E, Chen H H, Winer J, Houck K A, Ferrara N. Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR.  J Biol Chem. 1994;  269 25646-25654
    PubMedGoogle Scholar
  • 147 Vuorela P, Hatva E, Lymboussaki A et al.. Expression of vascular endothelial growth factor and placenta growth factor in human placenta.  Biol Reprod. 1997;  56 489-494
    CrossrefPubMedGoogle Scholar
  • 148 Rabbani M L, Rogers P A. Role of vascular endothelial growth factor in endometrial vascular events before implantation in rats.  Reproduction. 2001;  122 85-90
    CrossrefPubMedGoogle Scholar
  • 149 Rockwell L C, Pillai S, Olson C E, Koos R D. Inhibition of vascular endothelial growth factor/vascular permeability factor action blocks estrogen-induced uterine edema and implantation in rodents.  Biol Reprod. 2002;  67 1804-1810
    CrossrefPubMedGoogle Scholar
  • 150 Nayak N R, Brenner R M. Vascular proliferation and vascular endothelial growth factor expression in the rhesus macaque endometrium.  J Clin Endocrinol Metab. 2002;  87 1845-1855
    CrossrefPubMedGoogle Scholar
  • 151 Shifren J L, Tseng J F, Zaloudek C J et al.. Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis.  J Clin Endocrinol Metab. 1996;  81 3112-3118
    CrossrefPubMedGoogle Scholar
  • 152 Greb R R, Heikinheimo O, Williams R F, Hodgen G D, Goodman A L. Vascular endothelial growth factor in primate endometrium is regulated by oestrogen-receptor and progesterone-receptor ligands in vivo.  Hum Reprod. 1997;  12 1280-1292
    CrossrefPubMedGoogle Scholar
  • 153 Ancelin M, Buteau-Lozano H, Meduri G et al.. A dynamic shift of VEGF isoforms with a transient and selective progesterone-induced expression of VEGF189 regulates angiogenesis and vascular permeability in human uterus.  Proc Natl Acad Sci U S A. 2002;  99 6023-6028
    CrossrefPubMedGoogle Scholar
  • 154 Charnock-Jones D S, Sharkey A M, Rajput-Williams J et al.. Identification and localization of alternately spliced mRNAs for vascular endothelial growth factor in human uterus and estrogen regulation in endometrial carcinoma cell lines.  Biol Reprod. 1993;  48 1120-1128
    CrossrefPubMedGoogle Scholar
  • 155 Krussel J S, Casan E M, Raga F et al.. Expression of mRNA for vascular endothelial growth factor transmembraneous receptors Flt1 and KDR, and the soluble receptor sflt in cycling human endometrium.  Mol Hum Reprod. 1999;  5 452-458
    CrossrefPubMedGoogle Scholar
  • 156 Hornung D, Lebovic D I, Shifren J L, Vigne J L, Taylor R N. Vectorial secretion of vascular endothelial growth factor by polarized human endometrial epithelial cells.  Fertil Steril. 1998;  69 909-915
    CrossrefPubMedGoogle Scholar
  • 157 Ghosh D, Kumar P G, Sengupta J. Effect of early luteal phase administration of mifepristone (RU486) on leukaemia inhibitory factor, transforming growth factor beta and vascular endothelial growth factor in the implantation stage endometrium of the rhesus monkey.  J Endocrinol. 1998;  157 115-125
    CrossrefPubMedGoogle Scholar
  • 158 Ghosh D, Sharkey A M, Charnock-Jones D S et al.. Expression of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in conceptus and endometrium during implantation in the rhesus monkey.  Mol Hum Reprod. 2000;  6 935-941
    CrossrefPubMedGoogle Scholar
  • 159 Sengupta J, Lalitkumar P G, Najwa A R et al.. Immunoneutralization of vascular endothelial growth factor inhibits pregnancy establishment in the rhesus monkey (Macaca mulatta).  Reproduction. 2007;  133 1199-1211
    CrossrefPubMedGoogle Scholar
  • 160 Lessey B A, Castelbaum A J. Integrins and implantation in the human.  Rev Endocr Metab Disord. 2002;  3 107-117
    CrossrefPubMedGoogle Scholar
  • 161 Acosta A A, Elberger L, Borghi M et al.. Endometrial dating and determination of the window of implantation in healthy fertile women.  Fertil Steril. 2000;  73 788-798
    CrossrefPubMedGoogle Scholar
  • 162 Gonzalez R R, Palomino A, Boric A, Vega M, Devoto L. A quantitative evaluation of alpha1, alpha4, alphaV and beta3 endometrial integrins of fertile and unexplained infertile women during the menstrual cycle. A flow cytometric appraisal.  Hum Reprod. 1999;  14 2485-2492
    CrossrefPubMedGoogle Scholar
  • 163 Aplin J D. Adhesion molecules in implantation.  Rev Reprod. 1997;  2 84-93
    CrossrefPubMedGoogle Scholar
  • 164 Somkuti S G, Yuan L, Fritz M A, Lessey B A. Epidermal growth factor and sex steroids dynamically regulate a marker of endometrial receptivity in Ishikawa cells.  J Clin Endocrinol Metab. 1997;  82 2192-2197
    CrossrefPubMedGoogle Scholar
  • 165 Lessey B A. Two pathways of progesterone action in the human endometrium: implications for implantation and contraception.  Steroids. 2003;  68 809-815
    CrossrefPubMedGoogle Scholar
  • 166 Curry Jr T E, Osteen K G. The matrix metalloproteinase system: changes, regulation, and impact throughout the ovarian and uterine reproductive cycle.  Endocr Rev. 2003;  24 428-465
    CrossrefPubMedGoogle Scholar
  • 167 Alexander C M, Hansell E J, Behrendtsen O et al.. Expression and function of matrix metalloproteinases and their inhibitors at the maternal-embryonic boundary during mouse embryo implantation.  Development. 1996;  122 1723-1736
    PubMedGoogle Scholar
  • 168 Rinkenberger J L, Cross J C, Werb Z. Molecular genetics of implantation in the mouse.  Dev Genet. 1997;  21 6-20
    CrossrefPubMedGoogle Scholar
  • 169 Vu T H, Werb Z. Matrix metalloproteinases: effectors of development and normal physiology.  Genes Dev. 2000;  14 2123-2133
    CrossrefPubMedGoogle Scholar
  • 170 Anteby E Y, Greenfield C, Natanson-Yaron S et al.. Vascular endothelial growth factor, epidermal growth factor and fibroblast growth factor-4 and -10 stimulate trophoblast plasminogen activator system and metalloproteinase-9.  Mol Hum Reprod. 2004;  10 229-235
    CrossrefPubMedGoogle Scholar
  • 171 Taylor H S, Vanden Heuvel G B, Igarashi P. A conserved Hox axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the Hoxa cluster genes.  Biol Reprod. 1997;  57 1338-1345
    CrossrefPubMedGoogle Scholar
  • 172 Vitiello D, Kodaman P H, Taylor H S. HOX genes in implantation.  Semin Reprod Med. 2007;  25 431-436
    Article in Thieme ConnectPubMedGoogle Scholar
  • 173 Krumlauf R. Hox genes in vertebrate development.  Cell. 1994;  78 191-201
    CrossrefPubMedGoogle Scholar
  • 174 Benson G V, Lim H, Paria B C, Satokata I, Dey S K, Maas R L. Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression.  Development. 1996;  122 2687-2696
    PubMedGoogle Scholar
  • 175 Taylor H S, Arici A, Olive D, Igarashi P. HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium.  J Clin Invest. 1998;  101 1379-1384
    CrossrefPubMedGoogle Scholar
  • 176 Lim H, Ma L, Ma W G, Maas R L, Dey S K. Hoxa-10 regulates uterine stromal cell responsiveness to progesterone during implantation and decidualization in the mouse.  Mol Endocrinol. 1999;  13 1005-1017
    CrossrefPubMedGoogle Scholar
  • 177 Daftary G S, Taylor H S. Molecular markers of implantation: clinical implications.  Curr Opin Obstet Gynecol. 2001;  13 269-274
    CrossrefPubMedGoogle Scholar
  • 178 Accili D, Arden K C. FoxOs at the crossroads of cellular metabolism, differentiation, and transformation.  Cell. 2004;  117 421-426
    CrossrefPubMedGoogle Scholar
  • 179 Christian M, Zhang X, Schneider-Merck T et al.. Cyclic AMP-induced forkhead transcription factor, FKHR, cooperates with CCAAT/enhancer-binding protein beta in differentiating human endometrial stromal cells.  J Biol Chem. 2002;  277 20825-20832
    CrossrefPubMedGoogle Scholar
  • 180 Dijkers P F, Medema R H, Pals C et al.. Forkhead transcription factor FKHR-L1 modulates cytokine-dependent transcriptional regulation of p27(KIP1).  Mol Cell Biol. 2000;  20 9138-9148
    CrossrefPubMedGoogle Scholar
  • 181 Sunters A, Fernandez de Mattos S, Stahl M et al.. FoxO3a transcriptional regulation of Bim controls apoptosis in paclitaxel-treated breast cancer cell lines.  J Biol Chem. 2003;  278 49795-49805
    CrossrefPubMedGoogle Scholar
  • 182 Labied S, Kajihara T, Madureira P A et al.. Progestins regulate the expression and activity of the forkhead transcription factor FOXO1 in differentiating human endometrium.  Mol Endocrinol. 2006;  20(1) 35-44
    PubMedGoogle Scholar
  • 183 Chatzaki E, Makrigiannakis A, Margioris A N, Kouimtzoglou E, Gravanis A. The Fas/FasL apoptotic pathway is involved in kappa-opioid-induced apoptosis of human endometrial stromal cells.  Mol Hum Reprod. 2001;  7 867-874
    CrossrefPubMedGoogle Scholar
  • 184 Takeda K, Noguchi K, Shi W et al.. Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality.  Proc Natl Acad Sci U S A. 1997;  94 3801-3804
    CrossrefPubMedGoogle Scholar
  • 185 Cheng J G, Chen J R, Hernandez L, Alvord W G, Stewart C L. Dual control of LIF expression and LIF receptor function regulate Stat3 activation at the onset of uterine receptivity and embryo implantation.  Proc Natl Acad Sci U S A. 2001;  98 8680-8685
    CrossrefPubMedGoogle Scholar
  • 186 Salamonsen L A. Crosstalk between progesterone and interleukin-11 signal transduction pathways in human endometrial stromal cells during decidualization.  Reprod Fertil Dev. 2003;  15 73
    PubMedGoogle Scholar
  • 187 Underhill-Day N, McGovern L A, Karpovich N, Mardon H J, Barton V A, Heath J K. Functional characterization of W147A: a high-affinity interleukin-11 antagonist.  Endocrinology. 2003;  144 3406-3414
    CrossrefPubMedGoogle Scholar
  • 188 Dimitriadis E, Robb L, Liu Y X et al.. IL-11 and IL-11Ralpha immunolocalisation at primate implantation sites supports a role for IL-11 in placentation and fetal development.  Reprod Biol Endocrinol. 2003;  1 34
    CrossrefPubMedGoogle Scholar
  • 189 Corvinus F M, Fitzgerald J S, Friedrich K, Markert U R. Evidence for a correlation between trophoblast invasiveness and STAT3 activity.  Am J Reprod Immunol. 2003;  50 316-321
    CrossrefPubMedGoogle Scholar
  • 190 Kirchhof N, Carnwath J W, Lemme E, Anastassiadis K, Schöler H, Niemann H. Expression pattern of Oct-4 in preimplantation embryos of different species.  Biol Reprod. 2000;  63(6) 1698-1705
    CrossrefPubMedGoogle Scholar
  • 191 Avilion A A, Nicolis S K, Pevny L H, Perez L, Vivian L, Lovell-Badge R. Multipotent cell lineages in early mouse development depend on SOX2 function.  Genes Dev. 2003;  17(1) 126-140
    CrossrefPubMedGoogle Scholar
  • 192 Mitsui K, Tokuzawa Y, Itoh H et al.. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells.  Cell. 2003;  113(5) 631-642
    CrossrefPubMedGoogle Scholar
  • 193 Niwa H, Toyooka Y, Shimosato D et al.. Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation.  Cell. 2005;  123(5) 917-929
    CrossrefPubMedGoogle Scholar
  • 194 Hsieh-Li H M, Witte D P, Weinstein M et al.. Hoxa 11 structure, extensive antisense transcription, and function in male and female fertility.  Development. 1995;  121(5) 1373-1385
    PubMedGoogle Scholar
  • 195 Harris H A. Estrogen receptor-beta: recent lessons from in vivo studies.  Mol Endocrinol. 2007;  (1) 1-13
    CrossrefPubMedGoogle Scholar
  • 196 Mulac-Jericevic B, Mullinax R A, DeMayo F J, Lydon J P, Conneely O M. Subgroup of reproductive functions of progesterone mediated by progesterone receptor-B isoform.  Science. 2000;  289(5485) 1751-1754
    CrossrefPubMedGoogle Scholar
  • 197 Mulac-Jericevic B, Lydon J P, DeMayo F J, Conneely O M. Defective mammary gland morphogenesis in mice lacking the progesterone receptor B isoform.  Proc Natl Acad Sci U S A. 2003;  100(17) 9744-9749
    CrossrefPubMedGoogle Scholar
  • 198 Lydon J P, DeMayo F J, Funk C R et al.. Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.  Genes Dev. 1995;  9(18) 2266-2278
    CrossrefPubMedGoogle Scholar

Hugh S TaylorM.D. 

Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine

333 Cedar Street, New Haven, CT 06520-8063

Email: hugh.taylor@yale.edu

      >