Identification, Characterization, and Regulation of the Canonical Wnt Signaling Pathway in Human Endometrium

Tulač, Suzana; Nayak, Nihar R.; Kao, Lee-Chuan; Waes, Michael Van; Huang, Jian; Lobo, Shalini C; Germeyer, Ariane; Lessey, Bruce A.; Taylor, Robert N.; Suchanek, Ernest; Giudice, Linda C.

doi:10.1210/jc.2003-030494

Cited by 195 publications

(158 citation statements)

References 31 publications

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“…Additionally, recombinant Wnt-5a could not induce luciferase expression of the TCF reporter plasmid, suggesting that the accessory proteins required for Wnt-5a-induced canonical Wnt signalling [8] are lacking in trophoblasts. Interestingly, Wnt-5a expression has also been detected in early and late phase endometrium, suggesting that decidual expression of the ligand may exert paracrine effects on invading trophoblasts [14].…”

Section: Discussionmentioning

confidence: 99%

“…Several mRNAs encoding Wnt ligands and FZD receptors were detected in human term placenta [9][10][11][12][13]. In addition, endometrial expression of Wnt3 and Dickkopf-1 (Dkk1), which inhibits canonical Wnt signalling by disrupting binding of LRP-5/6 to the Wnt/FZD complex, was observed [14], suggesting paracrine mechanisms regulating implantation and/or trophoblast invasion. The TCF family members TCF-3 and TCF-4 are predominantly expressed in invasive trophoblasts and activation of the canonical Wnt signalling pathway promotes trophoblast migration and invasion [15].…”

Section: Introductionmentioning

confidence: 99%

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Complex Expression Pattern of Wnt Ligands and Frizzled Receptors in Human Placenta and its Trophoblast Subtypes

et al. 2007

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Canonical Wingless (Wnt) signalling provoked by exogenous and endogenous Wnt ligands was recently shown to play a crucial role in the invasive differentiation of human trophoblasts. To gain insights into the expression pattern of the developmental regulators, we analysed all human Wnt ligands and their frizzled (FZD) receptors in the human placenta and different trophoblast model systems using semi-quantitative PCR. Fourteen out of 19 Wnt ligands and 8 out of 10 FZD receptors were detectable in placental tissues, however, expression patterns varied with gestational age and between different trophoblast subtypes suggesting cell-specific functions. Besides Wnt ligands acting through the canonical pathway, non-canonical ligands such as Wnt-5a, which may also activate alternative Wnt signalling pathways or inhibit canonical Wnt signalling, could be identified. Western blot analyses revealed secretion of Wnt-5a from primary trophoblast cultures and trophoblastic cell lines. To evaluate the potential role of Wnt-5a, SGHPL-5 trophoblast cells were transfected with luciferase reporter plasmids harbouring eight T-cell factor (TCF) DNArecognition sequences which are exclusively activated through the canonical Wnt signalling pathway. Luciferase assays revealed that Wnt-3a-induced reporter activity was repressed by recombinant Wnt-5a indicating an antagonistic role in trophoblasts. The data suggest that a complex network of Wnt ligands and FZD receptors may regulate developmental processes of the human placenta.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Complex Expression Pattern of Wnt Ligands and Frizzled Receptors in Human Placenta and its Trophoblast Subtypes

et al. 2007

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“…DKK-1 is a potent inhibitor of the Wnt signaling pathway [69]. It was recently found to be specifically up-regulated by progesterone in in vitro decidualized endometrial stromal cells [70], was up-regulated in microarray study of mid-secretory endometrium [62] and downregulated in eutopic endometrium from women with endometriosis [52].…”

Section: Transcriptomic Approaches To Markers Of Uterine Receptivitymentioning

confidence: 99%

Uterine receptivity to human embryonic implantation: Histology, biomarkers, and transcriptomics

Aghajanova¹,

Hamilton²,

Giudice³

2008

Seminars in Cell & Developmental Biology

136

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Embryonic implantation is a dynamic process of paracrine interactions between the maternal compartment and the conceptus and involves a receptive endometrium and a developmentally competent blastocyst. Herein, we review histology, clinical approaches, and the promise of transcriptomics in elucidating mechanisms underlying implantation and development of biomarkers of uterine receptivity -with an eye to diagnose and treat implantation-based disorders of miscarriage, fetal growth restriction, pre-eclampsia, and infertility.Keywords human implantation; endometrium; microarray; blastocyst Challenges and approaches in studying the process of human implantation Clinical implicationsSuccessful embryo implantation is a crucial event in natural and assisted human reproduction. Blastocyst implantation is a dynamic process, involving embryo apposition, attachment to the maternal endometrial epithelium, and invasion into the endometrial stroma [1]. With in vitro fertilization (IVF), implantation failure can occur due to several factors [2], including embryonic defects such as chromosomal abnormalities, which are the most common cause of implantation failure [3,4]. Another widely acknowledged barrier to successful blastocyst implantation and, therefore, successful treatment of infertile women with implantation failure, is an inappropriately developed endometrium. It is well established that embryos cannot implant in a poorly matured endometrium [5], and this may be responsible for low implantation rates with transfer of "good quality" embryos. The success of embryonic implantation further relies upon cross-talk between the embryo and a receptive endometrium [5]. Optimization of IVF results are important for many reasons, and achieving optimal implantation is even more important in the setting of single embryo transfer, a common practice aimed to avoid multiple pregnancies.Corresponding author: Linda C. Giudice, MD, PhD, MSc, Professor and Chair, Department of Obstetrics, Gynecology and Reproductive Sciences, The Robert B. Jaffe, MD Endowed Professor in the Reproductive Sciences, University of California, San Francisco, 505 Parnassus Ave., M1496, Box 0132, San Francisco, CA 94143-0132, Tel: +1 4154762564, Fax: +1 415476181, giudice@obgyn.ucsf.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The implantation window and challenges of studying it NIH Public AccessThe endometrium is receptive to blastocyst implantation during a spatially and temporally restricted "window", when the luminal epithelium is favorable for blastocyst implantation even in the absence of an implanting ...

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“…It has been shown that endometrial receptivity could be modulated by a multitude of signaling molecules, including prostaglandins [3], growth factors, cytokines, chemokines, integrins, leukemia inhibitory factor [4,5], Wnt family ligands [6], and E-cadherin [7]. Whereas dysregulation of some of these factors could be associated with repeated implantation failure, key molecular mechanisms that underlie the regulation of endometrial receptivity remain to be elucidated [8].…”

Section: Introductionmentioning

confidence: 99%

Site-specific endometrial injury improves implantation and pregnancy in patients with repeated implantation failures

Huang

Wang

Soong

et al. 2011

Reprod Biol Endocrinol

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BackgroundTo test whether a site-specific hysteroscopic biopsy-induced injury in the endometrium during the controlled ovarian hyperstimulation cycle improves subsequent embryo implantation in patients with repeated implantation failure, a total of 30 patients who have had good responses to controlled ovulation stimulation but have failed to achieve pregnancy after two or more transfers of good-quality embryos were recruited in this prospective study.MethodsA single, site-specific hysteroscopic biopsy-induced injury was generated on the posterior endometrium at midline 10-15 mm from the fundus during the D4-D7 period of the ongoing controlled ovarian hyperstimulation cycle in six patients.ResultsPatients received endometrial biopsy protocol achieved a pregnancy rate of 100%. By contrast, only 46% of patients with similar clinical characteristics (N = 24) achieved pregnancy without the hysteroscopic biopsy-induced endometrium injury (p < 0.05).ConclusionsOur proof-of-concept study demonstrates that a site-specific hysteroscopic endometrium injury performed during the ongoing in vitro fertilization (IVF) cycle, instead of injuries received during prior cycles, significantly improves clinical outcomes in patients with repeated implantation failure.

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Identification, Characterization, and Regulation of the Canonical Wnt Signaling Pathway in Human Endometrium

Cited by 195 publications

References 31 publications

Complex Expression Pattern of Wnt Ligands and Frizzled Receptors in Human Placenta and its Trophoblast Subtypes

Complex Expression Pattern of Wnt Ligands and Frizzled Receptors in Human Placenta and its Trophoblast Subtypes

Uterine receptivity to human embryonic implantation: Histology, biomarkers, and transcriptomics

Site-specific endometrial injury improves implantation and pregnancy in patients with repeated implantation failures

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