Global Gene Expression Analysis to Identify Molecular Markers of Uterine Receptivity and Embryo Implantation

Reese, Jeff; Das, Sanjoy K.; Paria, Bibhash C.; Lim, Hyunjung Jade; Song, Haengseok; Matsumoto, Hiromichi; Knudtson, Kevin L.; DuBois, Raymond N.; Dey, Sudhansu K.

doi:10.1074/jbc.m107563200

Cited by 204 publications

(160 citation statements)

References 45 publications

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“…With the development of microarray technology, global approaches have been pursued to identify novel pathways involved in implantation events [51]. Five studies were published, within a short time frame, reporting the transcriptome human endometrium during the window of implantation [52][53][54][55][56] (Table 1).…”

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

138

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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: 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

138

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“…Thus, there have been several studies that have profiled gene expression patterns in the uterus after sex steroid hormone treatment of ovariectomized mice or of endometrial samples isolated at different stages of the menstrual cycle in humans (24)(25)(26)(27). In general these studies have taken RNA extracted from whole uterine tissue to profile.…”

Section: Complex Loading Onto the Chromatin Is Induced By E2 Andmentioning

confidence: 99%

Progesterone blocks estrogen-induced DNA synthesis through the inhibition of replication licensing

Pan

Deng

Pollard

2006

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

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In the uterus, progesterone (P4) acts early in G1 as a physiological inhibitor of estradiol-17␤ (E2)-induced epithelial cell proliferation. Gene expression profiling of uterine epithelial cell RNA isolated 3 h after hormonal treatment of ovariectomized mice revealed the co-coordinate down-regulation by P 4 of >20 genes whose functions are associated with DNA replication. This group included all of the minichromosome maintenance (MCM) proteins that are required for DNA replication licensing. E 2 regulated loading of these MCM proteins onto chromatin in parallel with its induction of DNA synthesis. E 2 caused this chromatin loading by retention of MCM proteins in the nucleus and through the induction of the loading factor Cdt1, which is necessary for the MCM heterohexamer to bind to the origin of DNA replication. P 4 dramatically reduced the binding of the MCMs to chromatin by a number of mechanisms. First, MCM mRNA and protein abundance was downregulated. Second, P 4 inhibited the E2 induction of Cdt1. Third, P4 treatment sequestered the normally nuclear MCM proteins into the cytoplasm. This reduced MCM binding resulted in the complete inhibition of E 2-induced DNA synthesis by P4. These data reveal mechanisms not only for female sex steroid hormone action but also in the regulation of DNA replication licensing.DNA replication ͉ minichromosome maintenance ͉ uterus ͉ cell cycle ͉ microarray I n uteri of mice and women, the female sex steroid hormones estradiol-17␤ (E 2 ) and progesterone (P 4 ) interact to regulate cell proliferation (1). In mice, E 2 synthesized at proestrus stimulates uterine luminal and glandular epithelial cell proliferation (2). In contrast, P 4 synthesized by corporea lutea formed after mating blocks the E 2 -induced epithelial cell proliferation but permits E 2 to induce a single wave of stromal cell division (3, 4). P 4 also induces differentiation of these epithelial cells so that they are receptive to the hatched blastocysts in order that implantation can proceed. These uterine cellular dynamics can be mimicked by administration of exogenous E 2 and P 4 to ovariectomized mice in regimens that parallel their physiological secretion (2,5,6). This hormone treatment provides a controllable model in which to study the mechanism of E 2 induction of cell proliferation in target epithelial tissues and also the action of a physiological inhibitor of cell division, in this case P 4 . These studies are highly relevant because exposure to the mitogenic effects of E 2 is thought to be the major risk factor for the development of endometrial and breast cancer (7).DNA replication needs to be a highly regulated process, and most cells seek to ensure one (and only one) round of replication per cell cycle. DNA synthesis is initiated by the formation of the prereplicative complex (pre-RC) at origins of replication during early G 1 , a process known as replication licensing (8, 9). Pre-RC formation involves the sequential assembly of Ͼ20 replication factors in a process that is largely conserved from yeast ...

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“…The two remaining studies compared the mRNA profiles of implantation and interimplantation sites, both tissue samples derived from pregnant uteri (Reese et al, 2001) or the mRNA profiles of whole uterine tissues from two different days of gestation (Yoshioka et al, 2000), respectively, thus, the studies substantially differ from the current study concerning their experimental design.…”

Section: Insulin-like Growth Factor Systemmentioning

confidence: 96%

“…day 18 of gestation. Only few other studies have been conducted so far to investigate genes involved in the process of embryonic implantation in the rhesus monkey (Sun et al, 2004) and in mice (Yoshioka et al, 2000;Reese et al, 2001), and this is to our knowledge the first study of this kind in the bovine species. A combination of subtracted cDNA libraries and cDNA array hybridization was applied to detect cDNAs of genes differentially expressed in the bovine endometrium of pregnant versus control animals at day 18 of gestation.…”

Section: Discussionmentioning

confidence: 99%

“…Sun et al (2004) performed suppression subtractive hybridization to find genes that are differentially expressed in the implantation site of the pregnant rhesus monkey uterus, Reese et al (2001) compared RNAs from implantation and interimplantation sites to identify genes that are specifically up-or downregulated at the implantation site in mice, and Yoshioka et al (2000) examined the expression of uterine genes before and after conceptus implantation in mice. There are very few genes mutually identified in one of the three studies mentioned above and in the current study, which deals with the identification of genes induced by the conceptus in the bovine endometrium during the pre-implantation period.…”

Section: Insulin-like Growth Factor Systemmentioning

confidence: 99%

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2 Identification of Genes Induced by the Conceptus in the Bovine Endometrium During the Pre-Implantation Period

Klein¹,

Bauersachs²,

Ulbrich³

et al. 2006

Reprod. Fertil. Dev.

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Early embryonic development, implantation, and maintenance of a pregnancy are critically dependent on an intact embryo-maternal communication. So far, only few signals involved in this dialogue have been identified. In ruminants, interferon tau (IFN�) plays a key role in the process of maternal recognition of pregnancy by exhibiting antiluteolytic activity. Even though many experimental findings indicate a pivotal role of IFN� in the context of embryo-maternal communication in ruminants, a number of other systems may be involved. To identify genes induced in the bovine endometrium by the signaling of the embryo, a combination of subtracted cDNA libraries and cDNA array hybridization was applied. Monozygotic twin pairs (n = 5) were used as the biological model. Pregnancy was created in one twin by transferring two in vitro-produced embryos on Day 7 of the estrous cycle; the other twin received a sham embryo transfer. Pregnant and nonpregnant twins were slaughtered at Day 18; endometrial tissue samples were recovered and processed for transcriptome analysis as described (Bauersachs et al. 2005 J. Mol. Endocrinol. 34, 889-908). Screening of 4608 clones of two subtracted libraries revealed 90 different up-regulated genes and mRNAs, of which almost 50% are known to be stimulated by type I interferons. Among these interferon-stimulated genes, the ISG15 system is assumed to be of particular interest, and several components were studied in more detail using in situ hybridization. The pattern of mRNA expression suggests that modification of endometrial proteins through ISG15ylation plays a fundamental role during the pre-implantation period. A classification of the identified genes based on Gene Ontologies revealed the prevalence of genes involved in regulation of gene expression, cell communication, cell growth, cell differentiation, cell proliferation, and cell adhesion, and also the prevalence of genes with immune-related functions. These results underline the intense response of the endometrium to the presence of a conceptus, culminating in the preparation of the maternal environment for embryonic implantation. Further, for eleven selected genes the expression in the endometrium was quantified by the use of real-time RT-PCR. Overall, the results of quantitative RT-PCR and array hybridization correlated very well. To our knowledge this study provides the first holistic gene expression analysis of the bovine endometrium during the pre-implantation period. The results underline the importance of IFN� as an embryo-derived pregnancy recognition signal and depict the molecular mechanisms at the mRNA level underlying the intense embryo-maternal dialog taking place at Day 18 of gestation.

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Global Gene Expression Analysis to Identify Molecular Markers of Uterine Receptivity and Embryo Implantation

Cited by 204 publications

References 45 publications

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

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

Progesterone blocks estrogen-induced DNA synthesis through the inhibition of replication licensing

2 Identification of Genes Induced by the Conceptus in the Bovine Endometrium During the Pre-Implantation Period

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