Expression of the repulsive SLIT/ROBO pathway in the human endometrium and Fallopian tube

Duncan, W C; McDonald, S E; Dickinson, R E; Shaw, J L V; Lourenco, P C; Wheelhouse, N; Lee, K-F; Critchley, H O D; Horne, A W

Abstract

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.

Citation

Duncan, W. C., McDonald, S. E., Dickinson, R. E., Shaw, J. L. V., Lourenco, P. C., Wheelhouse, N., …Horne, A. W. (2010). Expression of the repulsive SLIT/ROBO pathway in the human endometrium and Fallopian tube. Molecular Human Reproduction, 16, 950-959. https://doi.org/10.1093/molehr/gaq055

• Journal Article Type: Article
• Acceptance Date: Jun 22, 2010
• Online Publication Date: Jul 22, 2010
• Publication Date: Nov 22, 2010
• Deposit Date: Jul 21, 2016
• Journal: Molecular Human Reproduction
• Print ISSN: 1360-9947
• Electronic ISSN: 1460-2407
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 16
• Pages: 950-959
• DOI: https://doi.org/10.1093/molehr/gaq055
• Keywords: Endometrium, Decidua, Ectopic pregnancy, Chlamydia trachomatis, Smoking,
• Public URL: http://researchrepository.napier.ac.uk/Output/304711
• Related Public URLs: http://molehr.oxfordjournals.org/content/16/12/950.full.pdf