Human implantation: the last barrier in assisted reproduction technologies?

Edwards, Robert G.

doi:10.1016/s1472-6483(10)61039-5

Cited by 74 publications

(53 citation statements)

References 73 publications

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“…Many molecular markers such as integrins, IL-1, calcitonin, amphiregulin, EGF, HB (heparin binding)-EGF, colony stimulating factor-1, LIF, mucins, leptin, selectin-L ligands, Hoxa genes, and COX (cyclooxygenase) have been proposed to identify this period of receptivity [9,[38][39][40][41][42]. The beginning of the implantation window is also characterized by remarkable ultrastructural changes in endometrial epithelial cell morphology [31,32].…”

Section: Molecular and Structural Markers Of Endometrial Receptivitymentioning

confidence: 99%

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

Aghajanova¹,

Hamilton²,

Giudice³

2008

Seminars in Cell & Developmental Biology

140

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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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Section: Molecular and Structural Markers Of Endometrial Receptivitymentioning

confidence: 99%

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

Aghajanova¹,

Hamilton²,

Giudice³

2008

Seminars in Cell & Developmental Biology

140

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“…In reproductive aged women, there is only a 15% chance of pregnancy each cycle (1), and 75% of failed pregnancies are caused by implantation failure (2). The window of uterine receptivity is defined as the optimum time when the uterine endometrium is able to accept a blastocyst to implant.…”

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confidence: 99%

Aberrant activation of canonical Notch1 signaling in the mouse uterus decreases progesterone receptor by hypermethylation and leads to infertility

Strug

Jeong

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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In mammalian reproduction, implantation is one of the most critical events. Failure of implantation and the subsequent decidualization contribute to more than 75% of pregnancy losses in women. Our laboratory has previously reported that inhibition of Notch signaling results in impaired decidualization in both women and a transgenic mouse model. In this study, we generated a Notch gain-of-function transgenic mouse by conditionally overexpressing the Notch1 intracellular domain (N1ICD) in the reproductive tract driven by a progesterone receptor (Pgr) -Cre. We show that the overexpression of N1ICD in the uterus results in complete infertility as a consequence of multiple developmental and physiological defects, including the absence of uterine glands and dysregulation of progesterone and estrogen signaling by a Recombination Signal Binding Protein Jκ-dependent signaling mechanism. We further show that the inhibition of progesterone signaling is caused by hypermethylation of its receptor Pgr by Notch1 overexpression through the transcription factor PU.1 and DNA methyltransferase 3b (Dnmt3b). We have generated a mouse model to study the consequence of increased Notch signaling in female reproduction and provide the first evidence, to our knowledge, that Notch signaling can regulate epigenetic modification of the Pgr. mouse uterus | Notch1 | Pgr | methylation | infertility

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“…According to our previous observations and those of other groups, hCG plays important paracrine roles in implantation, angiogenesis and immune tolerance (Perrier d'Hauterive et al 2004Edwards 2006;Licht et al 2007;Rao and Lei 2007). Because of Fig.…”

Section: Discussionmentioning

confidence: 78%

Evidence for cross-talk between the LH receptor and LH during implantation in mice

Gridelet

Tsampalas

Berndt

et al. 2013

Reprod. Fertil. Dev.

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Abstract. The present study investigated the first interaction that occurs between the blastocyst and endometrium during implantation. Given the ethical objections to studying implantation in humans, a mouse model was used to study the dialogue between luteinising hormone (LH) and luteinising hormone receptor (LHCGR). Several studies performed on LHCGR-knockout mice have generated controversy regarding the importance of the dialogue between LH and LHCGR during implantation. There has been no demonstration of a bioactive LH-like signal produced by the murine blastocyst. The first aim of the present study was to examine and quantify, using radioimmunoassay, the generation of a bioactive LH signal by the murine blastocyst. We went on to examine and quantify endometrial Lhcgr expression to validate the mouse model. Expression of LHCGR in mouse uteri was demonstrated using immunohistochemistry and western blot analysis. To quantify the expression of Lh in the mouse blastocyst and Lhcgr in the endometrium, reverse transcription-polymerase chain reaction (RT-PCR) and real-time quantitative (q) RT-PCR were performed. The results demonstrate that Lhcgr expression in BALB/c mouse endometrial epithelium is increased at the time of implantation and indicate that LHCGR may contribute to the implantation process. In support of this hypothesis, we identified a bioactive LH signal at the time of murine blastocyst implantation.

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Human implantation: the last barrier in assisted reproduction technologies?

Cited by 74 publications

References 73 publications

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

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

Aberrant activation of canonical Notch1 signaling in the mouse uterus decreases progesterone receptor by hypermethylation and leads to infertility

Evidence for cross-talk between the LH receptor and LH during implantation in mice

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