Expression of mRNA for vascular endothelial growth factor in human placenta

Abstract

Implantation and growth of the placenta requires extensive angiogenesis to establish the vascular structures involved in exchange. Failure to establish adequate blood supply to the fetus may have serious clinical consequences such as intrauterine growth retardation. Vascular endothelial cell growth factor (VEGF) is a recently identified growth factor with significant angiogenic properties. We have demonstrated the presence of four species of mRNA encoding VEGF in both first trimester and term placenta. In situ hybridization was used to localize the sites of expression of VEGF mRNA in these tissues. VEGF expression was seen in villous trophoblast in the first trimester and in extravillous trophoblast at term, and in both fetal macrophages within the villi and maternal macrophages in the decidua. Glandular epithelium in maternal decidua also expressed VEGF mRNA. The strongest site of expression was in maternal macrophages adjacent to Nitabuch's stria, a zone of necrosis at the site of implantation. This complex pattern of expression suggests that VEGF is involved in angiogenesis on both maternal and fetal sides of the placenta and that macrophages are the primary source of VEGF. However, VEGF may also play a role in term placenta, when extensive angiogenesis has diminished, possibly regulating vascular permeability.

An Essential Role of the NF-κB/Toll-Like Receptor Pathway in Induction of Inflammatory and Tissue-Repair Gene Expression by Necrotic Cells

“…VEGF is an important mediator of angiogenesis, another key component of the tissue-repair pathway (12). Interestingly, VEGF expression could be detected in areas adjacent to necrotic cells in various disease models (13,14) and in situ analysis of tumor specimens also has demonstrated the localization of VEGF-producing cells proximal to necrotic foci (39). Our results indicate that necrotic cells may directly induce expression of VEGF and thus also participate in stimulating angiogenesis.…”

“…12). Interestingly, enhanced VEGF expression was detected in areas adjacent to necrotic cells in various disease models (13,14), although the inducing mechanisms are still largely uncharacterized. Two recent studies have proposed that necrotic cells, but not apoptotic cells, can potently induce dendritic cell (DC) maturation in vitro (15,16).…”

Differential Expression of Placental Villous Angiopoietin-1 and -2 During Early, Mid and Late Baboon Pregnancy

“…VEGF, Ang-1, Ang-2, and the Tie-2 receptor are expressed by cytotrophoblasts and syncytiotrophoblast as well as vascular and avascular cells within the human villous placenta [5][6][7][8][9], consistent with their proposed role upon placental vascular development. However, very little is known about the regulation of these respective angioregulatory factors within the villous placenta during human pregnancy.…”

The gonadotropins: Tissue-specific angiogenic factors?

“…Thus, not only fetal and placental vascular formation are dependent on VEGF expression, but also threshold levels of VEGF must be achieved for normal blood vessel formation to occur. VEGF was expressed in the villous trophoblast, the decidua and macrophages of both fetal and maternal origin (Sharkey et al, 1993;Ahmed et al, 1995;Vourela et al, 1997). During the first trimester, VEGF protein expression was localized to the cytotrophoblast in parallel with VEGFR-1 expression, suggesting an impact on trophoblast growth and differentiation in the first phase of gestation (Charnock-Jones et al, 1994;Ahmed et al, 1995).…”