A Genomic Approach to Identify Novel Progesterone Receptor Regulated Pathways in the Uterus during Implantation

Cheon, Yong-Pil; Li, Quanxi; Xu, Xueping; DeMayo, Francesco J.; Bagchi, Indrani C.; Bagchi, Milan K.

doi:10.1210/me.2002-0270

Cited by 124 publications

(130 citation statements)

References 43 publications

Supporting

Mentioning

125

Contrasting

Unclassified

Order By: Relevance

“…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.

View full text Add to dashboard Cite

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 ...

show abstract

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.

View full text Add to dashboard Cite

show abstract

“…In order to identify progesterone-regulated pathways in the uterus during implantation, mice were treated at day 3 of pregnancy with either RU486 (a progesterone receptor antagonist) or a vehicle (Cheon et al, 2002). Tissues were collected on day 4 of pregnancy and conducted to microarray analysis to determine the difference in gene expression.…”

Section: Maternal Recognition Of Pregnancy and The Pivotal Role Of Ifmentioning

confidence: 99%

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.

View full text Add to dashboard Cite

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.

show abstract

“…Several investigators reported the genes regulated by progesterone in the uterus with cDNA microarray [8,9]. Recently, gene targeting was used to create knockout mice for PR (PR knockout mouse: PRKO mouse) [10,11].…”

mentioning

confidence: 99%

Evidence for the Expression of Alcohol Dehydrogenase Class I Gene in Rat Uterus and Its Up-regulation by Progesterone

et al. 2008

View full text Add to dashboard Cite

Abstract. The endometrium is one of the target tissues of the ovarian steroid hormones, estrogen and progesterone. In order to elucidate the mechanism of gene regulation in the endometrium, suppressive subtraction hybridization was performed to isolate the candidate genes controlled by progesterone in rat uterus. Alcohol dehydrogenase (ADH) class I gene was one of the candidate genes. Here we investigated the expression and regulation of ADH class I gene in rat uterus. The mRNA of ADH class I was detected in uterus by RT-PCR using specific primers. Using specific probe for ADH class I, in situ hybridization was performed to investigate localization in rat uterus. Positive signals were detected in the endometrial stromal cells of rat uterus by in situ hybridization and were not detected in endometrial epithelial cells and myometrium in rat uterus. Ovariectomized rats were treated with 17-β estradiol and progesterone and the uteri of these rats were used for Northern blot analysis and assay of the ADH activity. Northern blot analysis revealed that the expression of ADH class I mRNA in rat uteri was up-regulated approximately two-fold after progesterone treatment, but not estrogen. Likewise, ADH activity was approximately two-fold higher in progesterone-treated rat uteri compared with controls. This study demonstrated that ADH class I gene is progesterone-responsive in the uterus. This implies that progesterone might be involved with retinoic acid synthesis in the uterus, since ADH is the key enzyme for retinoic acid synthesis.

show abstract

A Genomic Approach to Identify Novel Progesterone Receptor Regulated Pathways in the Uterus during Implantation

Cited by 124 publications

References 43 publications

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

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

Evidence for the Expression of Alcohol Dehydrogenase Class I Gene in Rat Uterus and Its Up-regulation by Progesterone

Contact Info

Product

Resources

About