Vascular endothelial growth factor localization in human ovary and fallopian tubes: possible role in reproductive function and ovarian cyst formation.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that also increases vascular permeability. We hypothesized that VEGF plays a role in the regulation of cyclic ovarian angiogenesis in women, and that its ability to increase vascular permeability may be an important factor in the production of fallopian tube effluent and fluid formation in ovarian cysts. To examine these hypotheses, we assessed VEGF expression in ovaries and fallopian tubes from premenopausal (n = 10) and postmenopausal (n = 4) women. Immunohistochemical analysis for VEGF was performed using a rabbit polyclonal antibody directed against human VEGF. In normal ovaries from premenopausal women, VEGF within healthy follicles was localized to the thecal cell layer, with minimal VEGF peptide detected in the granulosa cell layer. VEGF was not expressed in atretic follicles or a degenerating corpus luteum. However, intense VEGF immunostaining was observed within the highly vascularized corpora lutea in all specimens examined. In normal ovaries from postmenopausal women, VEGF was detected only in epithelial inclusion cysts and a serous cystadenoma. In specimens from both pre- and postmenopausal women, the luminal epithelium of the fallopian tube as well as smooth muscle cells and pericytes lining small and large blood vessels within the tube and hilum of the ovary exhibited specific staining for VEGF. Based on these data, we suggest that during reproductive life, VEGF plays a role in the growth and maintenance of the ovarian follicle and corpus luteum by mediating angiogenesis. In addition, VEGF within the fallopian tube luminal epithelium may increase vascular permeability and modulate tubal luminal secretions. Similarly, VEGF in the epithelial lining of benign ovarian neoplasms may contribute to fluid formation in ovarian cysts.