Document Detail


Expression of the repulsive SLIT/ROBO pathway in the human endometrium and Fallopian tube.
MedLine Citation:
PMID:  20651036     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated whether the repulsive SLIT/ROBO pathway is expressed in the endometrium and is negatively regulated during implantation. We also examined whether deficient expression in the Fallopian tube (FT) may predispose to ectopic pregnancy (EP). Endometrium (n = 21) and FT (n = 17) were collected across the menstrual cycle from fertile women with regular cycles. Decidualized endometrium (n = 6) was obtained from women undergoing termination, and FT (n = 6) was obtained from women with EP. SLIT/ROBO expression was quantified by reverse transcription-PCR and protein localized by immunohistochemistry. The regulation of SLIT/ROBO expression in vitro, by sex steroids and hCG, was assessed in endometrial (hTERT-EEpC) epithelial cells, and the effects of Chlamydia trachomatis infection and smoking were studied in oviductal (OE-E6/E7) epithelial cells. Endometrial SLIT3 was highest in the mid-secretory phase (P = 0.0003) and SLIT1,2 and ROBO1 showed a similar trend. ROBO2 was highest in proliferative phase (P = 0.027) and ROBO3,4 showed a similar trend. SLIT2,3 and ROBO1, 4 were lower in decidua compared with mid-secretory endometrium (P < 0.05). SLITs and ROBOs, excepting ROBO2, were expressed in FT but there were no differences across the cycle or in EP. SLIT/ROBO proteins were localized to endometrial and FT epithelium. Treatment of hTERT-EEpC with a combination of estradiol and medroxyprogesterone acetate inhibited ROBO1 expression (P < 0.01) but hCG had no effect. Acute treatment of OE-E6/E7 with smoking metabolite, cotinine, and C. trachomatis had no effect. These findings imply a regulated role for the endometrial SLIT/ROBO interaction during normal development and pregnancy but that it may not be important in the aetiology of EP.
Authors:
W C Duncan; S E McDonald; R E Dickinson; J L V Shaw; P C Lourenco; N Wheelhouse; K-F Lee; H O D Critchley; A W Horne
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-22
Journal Detail:
Title:  Molecular human reproduction     Volume:  16     ISSN:  1460-2407     ISO Abbreviation:  Mol. Hum. Reprod.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-03-16     Revised Date:  2011-07-28    
Medline Journal Info:
Nlm Unique ID:  9513710     Medline TA:  Mol Hum Reprod     Country:  England    
Other Details:
Languages:  eng     Pagination:  950-9     Citation Subset:  IM    
Affiliation:
Centre for Reproductive Biology, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4SB, UK. w.c.duncan@ed.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Cells, Cultured
Chlamydia Infections / metabolism
Decidua / metabolism
Embryo Implantation / physiology
Endometrium / metabolism*
Fallopian Tubes / metabolism*
Female
Gene Expression Regulation / drug effects
Genetic Predisposition to Disease
Humans
Intercellular Signaling Peptides and Proteins / analysis,  genetics,  metabolism
Nerve Tissue Proteins / analysis,  genetics,  metabolism*
Pregnancy
Pregnancy, Ectopic / genetics,  metabolism
Receptors, Cell Surface / analysis,  genetics,  metabolism
Receptors, Immunologic / analysis,  genetics,  metabolism*
Risk Factors
Signal Transduction / drug effects,  genetics*
Smoking / adverse effects
Grant Support
ID/Acronym/Agency:
G0802808(90914)//Medical Research Council; SCD/02//Chief Scientist Office; SCD/02//Chief Scientist Office; //Medical Research Council
Chemical
Reg. No./Substance:
0/Intercellular Signaling Peptides and Proteins; 0/Nerve Tissue Proteins; 0/ROBO2 protein, human; 0/ROBO3 protein, human; 0/ROBO4 protein, human; 0/Receptors, Cell Surface; 0/Receptors, Immunologic; 0/SLIT1 protein, human; 0/Slit homolog 2 protein; 0/roundabout protein
Comments/Corrections

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