Hum. Reprod. Advance Access originally published online on January 29, 2007
Human Reproduction 2007 22(4):927-937; doi:10.1093/humrep/del483
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Estradiol induces heparanase-1 expression and heparan sulphate proteoglycan degradation in human endometrium
1 Departments of General Surgery, Rush University Medical Center, Chicago, IL, USA 2 nstitute for the Study and Treatment of Endometriosis, Oak Brook, IL, USA 3 Department of Surgery, University of Chicago, Chicago, IL, USA 4 Rush Medical College, Chicago, IL, USA
5 To whom correspondence should be addressed at: Department of General Surgery, Rush University Medical Center, 1653 W. Congress Parkway, Chicago, IL 60612, USA. Tel: +1 312 942 6623; Fax: +1 312 942 2867; E-mail: xxu{at}rush.edu
BACKGROUND: This study seeks to determine whether estrogen is able to regulate the expression of heparanase-1 (HPR1) in human endometrium.
METHODS: HPR1 expression and heparan sulphate (HS) deposition in the endometrium collected in various menstrual phases were analysed by immunohistochemical and immunofluorescence staining, respectively. HPR1 expression in the endometrial cells unexposed or exposed to estradiol was analysed by using RT-PCR and luciferase reporter assay. HPR1 activity was analysed by using a novel enzyme-linked immunosorbent assay (ELISA). Cell surface HS levels were analysed by flow cytometry. Serum HPR1 activity in women receiving follicle-stimulating hormone (FSH) for IVF was measured by ELISA.
RESULTS: HPR1 expression was rarely detected in the endometrium in the early and mid-proliferative phases but was increased in the late proliferative phase and in the secretory phases. HPR1 expression was negatively associated with HS in the basement membrane (BM) of the endometrial glands. HPR1 gene expression, HPR1 promoter activity and HPR1 enzymatic activity were increased in the endometrial cells when exposed to 17
-estradiol (E2), whereas cell surface HS levels showed a decrease which could be blocked by PI-88, an HPR1 inhibitor. Serum HPR1 levels were increased in women with moderately elevated blood estrogen levels after receiving FSH.
CONCLUSIONS: HPR1 is differentially expressed in the endometrium in different menstrual phases. Estrogen plays an important role in inducing HPR1 expression, subsequently leading to HS degradation on the endometrial cell surface and in the BM of the endometrium.
Key words: endometrium/estradiol/heparanase/heparan sulphate/ovarian hyperstimulation syndrome
Submitted on August 7, 2006; resubmitted on September 22, 2006; resubmitted on November 11, 2006; accepted on November 29, 2006.
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