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Reproductive Sciences, Vol. 15, No. 5, 484-492 (2008)
DOI: 10.1177/1933719108314624

HB-EGF but Not Amphiregulin or Their Receptors HER1 and HER4 Is Altered in Endometrium of Women With Unexplained Infertility

Lusine Aghajanova, MD, PhD

Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco

Kerstin Bjuresten, BS

Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden

Signe Altmäe, BS

Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden

Britt-Marie Landgren, MD, PhD

Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden

Anneli Stavreus-Evers, PhD

Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden, anneli.stavreus-evers{at}kbh.uu.se

Heparin-binding epidermal growth factor—like growth factor (HB-EGF) and its receptors (HER1 and HER4) play a role in the human implantation process. Amphiregulin is a member of the EGF family but with unknown function in human fertility. It has been suggested that some women with unexplained infertility have defective endometrial development. The aim of this study is to determine the presence of amphiregulin and the receptors HER1 and HER4 in normal human endometrium throughout the menstrual cycle. In addition, the present study aims to compare endometrium from women with unexplained infertility with endometrium from women with male factor infertility and healthy fertile controls. Immunohistochemistry and real-time polymerase chain reaction were used to determine the expression of HB-EGF, HER1, HER4, and amphiregulin. The stromal staining of HER1 and the epithelial staining of HER4 were most intense in the mid- and late-secretory-phase endometrium. Amphiregulin did not vary during the menstrual cycle. In the mid-secretory phase, the protein expression of HB-EGF was lower in endometrium from women with unexplained infertility versus normal endometrium and endometrium from women with male factor infertility. HB-EGF and HER4 mRNA expression in mid-secretory endometrium of women with unexplained and male factor infertility were increased compared with normal controls. Impaired endometrial expression of certain members of the EGF family may contribute to infertility in some women with unexplained infertility.

Key Words: HB-EGF • HER1 • HER4 • human endometrium • unexplained infertility.


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