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Mol. Hum. Reprod. Advance Access originally published online on August 12, 2005
Molecular Human Reproduction 2005 11(8):543-551; doi:10.1093/molehr/gah207
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Expression of the epidermal growth factor system in human endometrium during the menstrual cycle

Kirsten Ejskjær1,5, B.S. Sørensen1, S.S. Poulsen2, O. Mogensen3, A. Forman4 and E. Nexø1

1Department of Clinical Biochemistry, NBG, Aarhus University Hospital, Århus, 2Department of Medical Anatomy, Panum Institute, University of Copenhagen, Copenhagen, 3Department of Gynecology and Obstetrics, Odense University Hospital, University of Southern Denmark, Odense and 4Department of Gynecology and Obstetrics, Skejby Sygehus, Aarhus University Hospital, Århus, Denmark

5 To whom correspondence should be addressed at: Department of Clinical Biochemistry, NBG, Aarhus University Hospital, Norrebrogade 44, 8000 Århus C, Denmark. E-mail: k.ejskjaer{at}dadlnet.dk

The epidermal growth factor (EGF) system is ubiquitous in humans and plays fundamental roles in embryogenesis, development, proliferation and differentiation. As the endometrium of fertile women is characterized by proliferation and differentiation, we hypothesize a role for the EGF system. Fourteen premenopausal women had endometrial samples removed on day 6 ± 1 and day 6 ± 1 and 12 ± 1 after ovulation during one menstrual cycle. RNA was extracted and analysed by real-time PCR, and immunohistochemistry was performed to localize the components of the EGF system. Human EGF Receptor 1 (HER1) showed highest expression during the proliferative phase, HER2 and HER4 during the early and HER3 during the late secretory phase. Amphiregulin (AR) and transforming growth factor alpha (TGF{alpha}) expression is highest in proliferative phase. Heparin binding (HB)-EGF and betacellulin (BCL) show no variation. Epiregulin (EP) is detectable in some samples. EGF is undetectable. HER1, HER2, HER3 and HER4 were localized to the epithelium and glands HER3 and HER4 solely in the secretory phase. Amphiregulin was seen in leucocytes and stromal cells, TGF{alpha} and betacellulin in the epithelial lining, epiregulin in stromal cells whereas HB-EGF and EGF are undetectable. In conclusions, we observed cyclical expression of the four EGF receptors and two ligands and localized all four receptors and four ligands in endometrial biopsies. This suggests a role for the EGF system in growth of the endometrium.

Key words: EGF receptors/epidermal growth factor/human endometrium/menstrual cycle


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