Expression of vascular endothelial growth factor (VEGF) during folliculogenesis and corpus luteum formation in the human ovary

Vascular endothelial growth factor (VEGF) has been suggested to be involved in angiogenesis and microvascular hyperpermeability. We examined immunohistochemically the expression of VEGF in the granulosa and theca cells, along with that of proliferating cell nuclear antigen (PCNA), in the vascular endothelium during the course of follicular development and corpora lutea formation in human ovaries. The immunolocalization of VEGF in these cells was compared with that of another putative angiogenic factor, basic fibroblast growth factor (bFGF). The granulosa cells in the primordial and primary follicles were VEGF negative, but at the preantral stage, the granulosa cells showed weakly positive immunostaining for VEGF. However, the VEGF immunostaining in the granulosa cells was weak throughout the folliculogenesis. In contrast, the theca interna cells of developing follicles showed strong staining for VEGF, which was well correlated with the PCNA positivity in the vascular endothelial cells in the thecal layer. In the atretic follicles, the granulosa and theca cells were VEGF negative. In the corpora lutea, VEGF was strongly expressed in both granulosa and theca lutein cells in the early luteal phase when the PCNA positivity in the endothelium increased, but the VEGF staining in these cells became weak in the mid- and late luteal phases. Accordingly, the PCNA positivity in the vascular endothelium was well correlated with the expression of VEGF in the theca cells during follicular development and atresia, and that in the granulosa and theca lutein cells in corpora lutea formation and regression. In addition, the immunolocalization of VEGF was different from that of bFGF.