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

Abstract

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 (TGFalpha) 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, TGFalpha 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.

Prenatal TCDD Exposure Delays Differentiation and Alters Cell Proliferation and Apoptosis in the Uterus of the Sprague-Dawley Rat

“…In the present study, there was a significant increase in protein expression of EGFR at 50 days, a known player associated with cell proliferation in the uterus [11]. As mentioned above, studies in our lab have associated uterine proliferation with increased levels of EGFR [15,16].…”

“…One pathway containing tyrosine kinases that has been implicated in the regulation of uterine proliferation and apoptosis is the epidermal growth factor (EGF) pathway [11]. EGF and its receptors, the ErbB family of tyrosine kinases that includes epidermal growth factor receptor (EGFR), form a network that is known to play a role in cell proliferation in many tissue types.…”

Innate Immunity in the Female Reproductive Tract: Role of Sex Hormones in Regulating Uterine Epithelial Cell Protection Against Pathogens

“…In contrast, Ejskjaer et al were unable to detect EGF in endometrial samples [57]. This discrepancy may be due to different collection times in that Ejskjaer et al did not examine any samples during ovulation [55,57].…”

“…Studies have shown that EGF expression fluctuates during the menstrual cycle with expression highest during the late proliferative and secretory phases [55,56]. In contrast, Ejskjaer et al were unable to detect EGF in endometrial samples [57]. This discrepancy may be due to different collection times in that Ejskjaer et al did not examine any samples during ovulation [55,57].…”

The Role of ErbB Receptors in Endometrial Cancer

“…EGFR, in endometrium, is localized to the basal part of surface epithelial cells, only in stromal cells, or both to epithelial and stromal cells [Bigsby et al, 1992;Wang et al, 1994;Imai et al, 1995;Möller et al, 2001;Ejskjaer et al, 2005]. It is primarily located to the cell membrane but also to the cytoplasm [Nyholm et al, 1993;Reinartz et al, 1994;Khalifa et al, 1994;Niikura et al, 1996;Ejskjaer et al, 2007].…”