Transcriptional Regulation of the Placental Lactogen Genes in Mouse Trophoblast Giant Cells

1993 ◽  
pp. 243-252 ◽  
Author(s):  
Miho M. Shida ◽  
Yuk-Kiu Ng ◽  
Daniel I. H. Linzer
2000 ◽  
Vol 165 (2) ◽  
pp. 443-456 ◽  
Author(s):  
TJ Peters ◽  
BM Chapman ◽  
MW Wolfe ◽  
MJ Soares

Trophoblast giant cells are one of the primary endocrine cell types of the rodent placenta. Placental lactogen-I (PL-I) is the initial prolactin (PRL) family member expressed as trophoblast giant cells differentiate. In this report, we use the Rcho-1 trophoblast cell line as a model for studying the regulation of PL-I gene expression during trophoblast giant cell differentiation. Evidence is provided for trophoblast cell expression of epidermal growth factor receptor (EGFR), ErbB2, fibroblast growth factor receptor 1 (FGFR1), transforming growth factor-alpha, and heparin-binding EGF. EGF and FGF-2 stimulated PL-I mRNA and protein accumulation and PL-I promoter activity in a concentration-dependent manner. These latter growth factor actions on PL-I promoter activities were specifically inhibited by cotransfection with dominant negative constructs for EGFR and FGFRs respectively. Utilization of the mitogen-activated protein kinase (MAPK) pathway by EGF and FGF-2 in trophoblast cells was demonstrated by growth factor stimulation of a Gal4 DNA binding/Elk1 transactivational domain fusion construct, and more specifically by activation of extracellular signal regulated kinase and p38 MAPK. PL-I gene activation was also sensitive to disruption of MAPK and activation protein-1 (AP-1) signaling pathways. In conclusion, autocrine/paracrine pathways involving EGFR and FGFR1, MAPK and AP-1 are shown to participate in the regulation of the PL-I gene in differentiating trophoblast cells.


Development ◽  
1997 ◽  
Vol 124 (4) ◽  
pp. 907-914 ◽  
Author(s):  
G.T. Ma ◽  
M.E. Roth ◽  
J.C. Groskopf ◽  
F.Y. Tsai ◽  
S.H. Orkin ◽  
...  

We previously demonstrated that the zinc finger transcription factors GATA-2 and GATA-3 are expressed in trophoblast giant cells and that they regulate transcription from the mouse placental lactogen I gene promoter in a transfected trophoblast cell line. We present evidence here that both of these factors regulate transcription of the placental lactogen I gene, as well as the related proliferin gene, in trophoblast giant cells in vivo. Placentas lacking GATA-3 accumulate placental lactogen I and proliferin mRNAs to a level 50% below that reached in the wild-type placenta. Mutation of the GATA-2 gene had a similar effect on placental lactogen I expression, but led to a markedly greater reduction (5- to 6-fold) in proliferin gene expression. Placentas lacking GATA-2 secrete significantly less angiogenic activity than wild-type placentas as measured in an endothelial cell migration assay, consistent with a reduction in expression of the angiogenic hormone proliferin. Furthermore, within the same uterus the decidual tissue adjacent to mutant placentas displays markedly reduced neovascularization compared to the decidual tissue next to wild-type placentas. These results indicate that GATA-2 and GATA-3 are important in vivo regulators of trophoblast-specific gene expression and placental function, and reveal a difference in the effect of these two factors in regulating the synthesis of related placental hormones.


1991 ◽  
Vol 44 (2) ◽  
pp. 327-331 ◽  
Author(s):  
Teresa N. Faria ◽  
Linda Ogren ◽  
Frank Talamantes ◽  
Daniel I. H. Linzer ◽  
Michael J. Soares

Reproduction ◽  
2004 ◽  
Vol 128 (1) ◽  
pp. 53-71 ◽  
Author(s):  
A H K El-Hashash ◽  
S J Kimber

Differentiation of trophoblast giant cells is an early event during the process of murine embryo implantation. However, differentiation of secondary trophoblast giant cells in the rodent is still only partially understood, probably because of the lack of suitablein vitromodels and cell markers. In order to advance our understanding of trophoblast differentiation, suitablein vitromodels and markers are required to study their development. The objectives of this study were to establish and characterise a serum-freein vitromodel for murine secondary trophoblast cells. Secondary trophoblast giant cells growingin vitroand paraffin sections of day 8.5 postcoitum mouse embryos were processed for immunostaining to establish the expression of potential markers using antibodies to blood group antigens, E-cadherin, α7integrins and activator protein-γ, as well as placental lactogen-II. Within 3 days in serum-free culture, ectoplacental cone-derived secondary trophoblast cells underwent simultaneous induction of both morphological and functional differentiation. Secondary trophoblasts grewin vitroas a monolayer of cells with giant nuclei and expressed B and Le-b/Le-y blood group antigens, α7integrins and placental lactogen-II, as well as activator protein-γ. Transcripts for activator protein-γ and placental lactogen-II were detected in cultures by RT-PCR and for placental lactogen-II byin situhybridisation. At later time-points apoptosis increased. A fibronectin substrate significantly increased secondary trophoblast cell numbers and surface area of outgrowth. The increase in cells with giant nuclei coincided with induction of placental lactogen-II expression. A relationship was found between the nuclear area of secondary trophoblast cells and expression of placental lactogen-II.


1998 ◽  
Vol 12 (3) ◽  
pp. 418-427 ◽  
Author(s):  
Jiandie Lin ◽  
Daniel I. H. Linzer

Abstract Placental lactogen II, the major ligand for the PRL receptor during the second half of gestation in rodents, is synthesized specifically by placental trophoblast giant cells. A transient transgenic analysis has been used to localize the giant cell-specific regulatory region within the mouse placental lactogen II gene to sequences between −1340 and −2019 upstream of the transcriptional start site. More precise mapping of the regulatory elements has been accomplished by transfection of promoter constructs into Rcho-1 trophoblast cells, resulting in the characterization of two positive regulatory elements in the −1471 to −1340 region; two other regulatory elements have been implicated but not further characterized, a negative regulatory element between −2019 and −1778 and another positive element within the region from −1340 to −569. Both of the characterized positive regulatory elements are recognized by factors that are enriched in differentiated giant cells compared with proliferative trophoblasts, and these factors are either absent or at low levels in fibroblasts. The complexes that form on the two elements are distinct and neither element competes with the other for factor binding, thus implicating at least two different regulatory elements in late-gestational trophoblast giant cell-specific gene expression.


Development ◽  
1981 ◽  
Vol 61 (1) ◽  
pp. 277-287
Author(s):  
A. J. Copp

The number of trophoblast giant cells in outgrowths of mouse blastocysts was determined before, during and after egg-cylinder formation in vitro. Giant-cell numbers rose initially but reached a plateau 12 h before the egg cylinder appeared. A secondary increase began 24 h after egg-cylinder formation. Blastocysts whose mural trophectoderm cells were removed before or shortly after attachment in vitro formed egg cylinders at the same time as intact blastocysts but their trophoblast outgrowths contained fewer giant cells at this time. The results support the idea that egg-cylinder formation in vitro is accompanied by a redirection of the polar to mural trophectoderm cell movement which characterizes blastocysts before implantation. The resumption of giant-cell number increase in trophoblast outgrowths after egg-cylinder formation may correspond to secondary giant-cell formation in vivo. It is suggested that a time-dependent change in the strength of trophoblast cell adhesion to the substratum occurs after blastocyst attachment in vitro which restricts the further entry of polar cells into the outgrowth and therefore results in egg-cylinder formation.


Placenta ◽  
2013 ◽  
Vol 34 (9) ◽  
pp. A8
Author(s):  
Roberta Hannibal ◽  
Edward Chuong ◽  
Juan Carlos Rivera Mulia ◽  
David Gilbert ◽  
Anton Valouev ◽  
...  

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