Vascular endothelial growth factor (VEGF) in endometriosis

Abstract

Angiogenesis is likely to be involved in the pathogenesis of endometriosis. According to the transplantation theory, when the exfoliated endometrium is attached to the peritoneal layer, the establishment of a new blood supply is essential for the survival of the endometrial implant and development of endometriosis. From the known angiogenic factors, vascular endothelial growth factor (VEGF) has emerged as a pivotally important regulator of normal angiogenesis and pathological neovascularization. The VEGF protein was evaluated immunohistochemically in the eutopic endometrium of 10 women without endometriosis (group I) at laparoscopy and the eutopic endometrium and peritoneal endometriotic lesions of 43 women with endometriosis (group II). VEGF histological scores were 9.7 +/- 4.3 and 4.0 +/- 2.6 respectively in the epithelium and stroma of the eutopic endometrium of group I women, and 10.3 +/- 2.3 and 3.6 +/- 2.3 respectively in women of group II. In red lesions, the VEGF scores were 11.1 +/- 3.0 in the epithelium and 5.1 +/- 3.0 in the stroma, and in black lesions were 8.6 +/- 2.7 and 1.6 +/- 1.6, respectively. Significantly lower values were observed in black lesions as compared with eutopic endometrium and red lesions, the values of which were similar. Scores were also evaluated according to the phase of the cycle. In eutopic as well as ectopic endometrium, no significant cyclic variations were observed throughout the cycle. However, VEGF content was found to be higher in the eutopic glandular epithelium of women with endometriosis during the late secretory phase, possibly suggesting a more likely tendency to implant. In contrast, significantly higher VEGF content was noted in red lesions as compared with black lesions. During all phases of the cycle, the VEGF content in stromal cells of red lesions was higher than in black lesions. Similarities in VEGF content were observed in the glandular epithelium of the eutopic endometrium of women with endometriosis and red lesions, suggesting that endometriosis probably arises from the peritoneal seeding of viable endometrial cells during retrograde menstruation and that red lesions can be considered as the first stage of implantation. After the attachment phase, the high VEGF levels could provoke an increase in the subperitoneal vascular network and facilitate implantation and viability in the retroperitoneal space. Lower VEGF levels in black lesions explain the decrease in both stromal vascularization, followed by fibrosis and inactivation of the implant.

The relationship between microvessel density, proliferative activity and expression of vascular endothelial growth factor-A and its receptors in eutopic endometrium and endometriotic lesions

“…VEGF-A seems to be one of the most important angiogenic growth factors in the regulation of angiogenesis in general and probably also in both eutopic and ectopic endometrium (Li et al 1994, McLaren et al 1996b, Shifren et al 1996, Torry et al 1996, Donnez et al 1998, Mö ller et al 2001. We can show that VEGF-A and its receptors VEGFR-1 and VEGFR-2 are present in both eutopic and ectopic endometrium, and their relation to microvessel density and proliferative activity will be discussed later.…”

“…This includes aromatase activity in the eutopic endometrium from women with moderate to severe endometriosis, but not in those of disease-free women (Noble et al 1996). There is also a higher VEGF-A content in the secretory phase eutopic glandular epithelium (Donnez et al 1998) and an elevated endothelial cell proliferation in women with endometriosis (Wingfield et al 1995), compared with those without. Accumulated data thus suggest that eutopic endometrium of women with endometriosis behaves differently from the endometrium of women without the disease.…”

The effects of ergot and non-ergot-derived dopamine agonists in an experimental mouse model of endometriosis

“…Numerous peritoneal blood vessels surround active endometriotic lesions, and the implant itself is also endowed with a rich vascularized area; this can be observed under histological examination (Nisolle et al 1993, Nap et al 2004 and confirms the essential role that angiogenesis plays in the development and continuation of endometriotic lesions (Shifren et al 1996, Donnez et al 1998, Becker et al 2005. In this regard, it has been observed that human endometrium engrafted in immunocompromised mice promotes the growth of neovessels from the surrounding host vascular network in order to provide the endometriotic lesions with an adequate blood supply.…”

Endometrial Stromal Cells and Immune Cell Populations Within Lymph Nodes in a Nonhuman Primate Model of Endometriosis

“…Endometriosis has invasive characteristics as endometrial tissue must attach to and invade the peritoneum, establish a blood supply, and continue to proliferate to form an ectopic lesion. [12][13][14][15] Understanding lymphatic drainage is considered crucial in diagnosis, prognosis, and treatment of invasive diseases. Also, lymphatic spread is hypothesized to play a role in pathogenesis of endometriosis and is thought to account for displacement of endometrial cells at unusual locations, other than those that would otherwise be accessible to retrograde menstrual flow.…”