Vascular endothelial growth factor messenger ribonucleic acid expression in the primate ovary.

Abstract

We studied the distribution of messenger RNA (mRNA) that encodes for vascular endothelial growth factor (VEGF) within the primate ovary by in situ hybridization and Northern analysis to determine if the presence of mRNA for this angiogenic factor is associated with structures within the ovary in which angiogenesis is thought to play a role in development and/or function. In situ hybridization to sections of cynomolgus ovaries with a 35S-labeled antisense RNA probe revealed specific tissue localization within the follicle as well as the corpus luteum, but not stromal tissue. Intense expression of mRNA for VEGF during the late follicular phase was confined to the maturing follicle which, we presume, was destined for ovulation. Hybridization within the corpus luteum exhibited a punctate pattern suggesting that there may be specific cells within the corpus luteum that express mRNA for VEGF. The expression of mRNA for VEGF during the early and late luteal phase of the menstrual cycle was studied by Northern analysis. Messenger RNAs were detectable at approximately 3.7 and 5.0 kb positions in corpora lutea collected during the early luteal phase of the menstrual cycle (days 3-5 postovulation). No hybridization signals were observed with RNA prepared from regressing corpora lutea (1-2 days following the onset of menses). The gonadotropic regulation of the expression of mRNA for VEGF in the corpus luteum was studied by treating monkeys with a potent GnRH antagonist during the midluteal phase of the menstrual cycle. Administration of the antagonist for 1 or 2 days did not alter the expression of mRNA for VEGF in comparison to corresponding controls. However, a 3-day treatment regimen brought about a significant reduction in the levels of mRNA for VEGF (P less than 0.01). These studies demonstrate a development-related expression of mRNA for VEGF in the ovary during the menstrual cycle and are consistent with the hypothesis that VEGF may play important roles in follicle selection and corpus luteum function in primates.

Vascular endothelial growth factor increases messenger RNAs encoding cyclooxygenase-II and membrane-associated prostaglandin E synthase in rat luteal cells

“…Several mechanisms are involved in regulating VEGF gene expression in the ovary (Ravindranath et al 1992, Neulen et al 1995, Christenson & Stouffer 1997, Pai et al 2001. PGE 2 -elicited cAMP is known to be one of the mediators of VEGF expression (Lopez Bernal et al 1995).…”

Ovariectomy improves neovascularization and microcirculation of freely transplanted ovarian follicles

“…For bilaterally ovariectomized hamsters, it has been shown that both serum LH and FSH concentrations are significantly elevated when compared with unmanipulated animals (Bex & Goldman 1975). Studies in the rat (Dissen et al 1994) and non-human primate (Ravindranath et al 1992) suggest that LH modulates expression of VEGF. Moreover, the rapid increase in Figure 6 Quantification of (A) vascularized area (as percent of the intial follicular size), (B) follicular growth (as percent of the initial follicular size), and (C) microvessel density of follicles after free transplantation into hamster dorsal skinfold chambers, as assessed by intravital fluorescence microscopy and computer-assisted image analysis.…”

VEGF and bFGF increase survival of xenografted human ovarian tissue in an experimental rabbit model

“…Basic fibroblast growth factors (bFGF) is one of the FGF family, and it plays important roles in various developmental processes, such as stimulating endothelial cells migration and mitosis, maintaining granulosa cell viability during follicular development. In ovary, VEGF and bFGF are expressed by granulosa and theca cells, as well as the corpus luteum and may be involved in the follicular development [15,16]. bFGF also has been shown to protect cells, including cultured granulosa cells from undergoing cell death [17].…”