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

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Abstract

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.

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Authors and Affiliations

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

    Lusine Aghajanova MD, PhD, Kerstin Bjuresten BS, Signe Altmäe BS, Britt-Marie Landgren MD, PhD & Anneli Stavreus-Evers PhD

  2. Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, USA

    Lusine Aghajanova MD, PhD

  3. Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden

    Anneli Stavreus-Evers PhD

Authors
  1. Lusine Aghajanova MD, PhD
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  2. Kerstin Bjuresten BS
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  3. Signe Altmäe BS
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  4. Britt-Marie Landgren MD, PhD
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  5. Anneli Stavreus-Evers PhD
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Corresponding author

Correspondence to Anneli Stavreus-Evers PhD.

Additional information

This work was supported by grants from the Swedish Research Council (2005-7293), the Swedish Society of Medicine, Karolinska Institutet, the Goljes Foundation, and the Åke Wibergs Foundation. The authors thank Helen Davidson for language revision.

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Aghajanova, L., Bjuresten, K., Altmäe, S. et al. HB-EGF but Not Amphiregulin or Their Receptors HER1 and HER4 Is Altered in Endometrium of Women With Unexplained Infertility. Reprod. Sci. 15, 484–492 (2008). https://doi.org/10.1177/1933719108314624

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