HB-EGF but not amphiregulin or their receptors HER1 and HER4 is altered in endometrium of women with unexplained infertility

Abstract

Background: 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. Aim: 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 aimed to compare endometrium from women with unexplained infertility with endometrium from women with male factor infertility and healthy fertile controls. Methodology: Immunohistochemistry and real-time PCR were used to determine the expression of HB-EGF, HER1, HER4 and amphiregulin. Result: 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 mid-secretory phase, the protein expression of HB-EGF was lower in endometrium from women with unexplained infertility vs. 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 was increased compared to normal controls. Conclusion: Impaired endometrial expression of certain members of the EGF family may contribute to infertility in some women with unexplained infertility