Document Detail


Galectin-1 markedly reduces the incidence of resorptions in mice missing immunophilin FKBP52.
MedLine Citation:
PMID:  22416080     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Progesterone (P(4)) signaling is critical for pregnancy. We previously showed that immunopilin FK506 binding protein (FKBP)52 serves as a cochaperone to optimize progesterone receptor (PR) function in the uterus, and its deficiency leads to P(4) resistance in a pregnancy stage-specific and genetic background-dependent manner in mice. In particular, sc placement of SILASTIC implants carrying P(4) rescued implantation failure in CD1 Fkbp52(-/-) mice, but the resorption rate was substantially high at midgestation due to reduced P(4) responsiveness. Because downstream targets of P(4)-FKBP52-PR signaling in the uterus to support pregnancy are not clearly understood, we performed proteomic analysis using Fkbp52(-/-), PR-deficient (Pgr(-/-)), and wild-type (WT) uteri. We found that the expression of galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, was significantly down-regulated in both Fkbp52(-/-) and Pgr(-/-) uteri compared with WT uteri. During early gestation, Lgals1, which encodes Gal1, was distinctly expressed in stromal and decidual cells. Lgals1 expression was much lower in d 4 Fkbp52(-/-) uteri compared with WT uteri, and this reduction was reversed by P(4) supplementation. More interestingly, concomitant supplementation of recombinant Gal1 significantly suppressed the high resorption rate and leukocyte infiltration at implantation sites in CD1 Fkbp52(-/-) females carrying P(4) SILASTIC implants. These findings suggest that uterine Gal1 is an important downstream target of P(4)-FKBP52-PR signaling in the uterus to support P(4) responsiveness during pregnancy.
Authors:
Yasushi Hirota; Kristin E Burnum; Nuray Acar; Gabriel A Rabinovich; Takiko Daikoku; Sudhansu K Dey
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-13
Journal Detail:
Title:  Endocrinology     Volume:  153     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-23     Completed Date:  2012-06-29     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2486-93     Citation Subset:  AIM; IM    
Affiliation:
Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Embryo Implantation / physiology
Female
Galectin 1 / genetics,  metabolism*
Mice
Mice, Knockout
Pregnancy
Proteomics
Receptors, Progesterone / genetics,  metabolism*
Stromal Cells / metabolism
Tacrolimus Binding Proteins / genetics,  metabolism*
Uterus / metabolism*
Grant Support
ID/Acronym/Agency:
HD068524/HD/NICHD NIH HHS; HD12304/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Galectin 1; 0/Receptors, Progesterone; EC 5.2.1.-/Tacrolimus Binding Proteins; EC 5.2.1.8/FKBP6 protein, mouse
Comments/Corrections

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