Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2005-6-15
pubmed:abstractText
Activation of the receptors for leukemia inhibitory factor (LIF) and IL-11 is essential for embryo attachment and decidualization in mice. Both receptors induce activation of the Stat family of signal transducers via the Jak/Stat pathway. Here, we aimed to establish whether activation of Stat3 in maternal endometrium is essential for successful implantation. Functional blockade of Stat3 before implantation, by injection into the uterine lumen of a cell-permeable Stat3 peptide inhibitor, reduced embryo implantation specifically by 70% (P < 0.001). Stat3 is phosphorylated in the luminal epithelium (LE) in response to LIF, and this phosphorylation was significantly reduced both in vitro and in vivo by the Stat3 inhibitor. The inhibitor also blocked induction by LIF of several LIF-regulated genes in the LE including Irg1, which has been shown previously to be essential for implantation. Successful implantation is therefore dependent on phosphorylation and activation of Stat3 in the endometrium before implantation. This finding provides a target for contraceptive development, based on selective blockade of signal transduction pathways essential for implantation. This study demonstrates that cell-permeable peptide inhibitors can be used effectively to target intracellular signaling pathways in the uterine LE.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-10477521, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-10729316, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-10857556, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-10906057, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-11108244, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-11438698, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-11457894, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-11579100, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-12080006, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-12456805, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-12639546, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-12649187, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-12837923, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-12865319, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-1425442, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-14500577, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-14500688, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-14657014, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-15178747, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-1522892, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-1722331, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-3541745, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-7574495, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-7701321, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-8345076, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-8371101, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-8608586, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-9022056, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-9108058, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-9192639, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-9421431, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-9500603, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-9716487, http://linkedlifedata.com/resource/pubmed/commentcorrection/15937114-9858499
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
102
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8585-90
pubmed:dateRevised
2010-9-20
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Inhibition of Stat3 activation in the endometrium prevents implantation: a nonsteroidal approach to contraception.
pubmed:affiliation
Reproductive Molecular Research Group, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom. rc296@cam.ac.uk
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't