Abstract
BackgroundPre-eclampsia remains a dominant cause of maternal and fetal mortality in developed countries. In a previous prospective study we identified a fall in the VEGF-A isoform VEGF-A165b in the plasma of patients in the first trimester to be a predictor of later pre-eclampsia. VEGF-A165b has been shown to have potent cytoprotective properties in many cell types. We therefore tested the hypothesis that VEGF-A165b may be cytoprotective for placental trophoblasts.MethodsWe used an immortalised first trimester trophoblast cell line exposed to chemical toxicity, and physiological (<2% O2) and atmospheric oxygen (21% O2) in the presence or absence of VEGF-A165b, angiogenic VEGF-A165a, a non-specific anti-VEGF-A blocking antibody (bevacizumab), or a specific anti-VEGF-A165b antibody. Cell viability and cytotoxicity were measured by trypan blue and LDH assay respectively.ResultsUnder high (21%) levels of oxygen, trophoblast viability was increased, and cytotoxicity reduced by exogenous recombinant VEGF-A165b (p < 0.05, n = 10) or VEGF-A165a. The cytoprotective effect was not seen under lower (<2%) oxygen conditions, where VEGF-A165b was upregulated. However inhibition of VEGF-A with blocking antibodies (bevacizumab or anti-VEGF-A165b) had marked cytotoxic effects under low oxygen conditions presumably through the blockade of autocrine survival pathways.ConclusionsThese results show that when trophoblasts are exposed to lower oxygen tensions (as they are early in the 1st trimester) endogenous VEGF-A165b contributes to their survival through an autocrine pathway. In contrast in high oxygen conditions exogenous VEGF-A isoforms have a greater effect on trophoblast survival.
Highlights
Pre-eclampsia remains a dominant cause of maternal and fetal mortality in developed countries
VEGF-A165b is cytoprotective for trophoblasts To determine whether exogenous VEGF-A165b was cytoprotective for placental trophoblasts, 1 × 105 HTR-8/ SVneo trophoblast cells were cultured in serum free medium (SFM) ± 1nM VEGF-A165b for 48 hours in atmospheric oxygen (n = 10)
Viability of cells exposed to VEGF-A165b, measured by trypan blue exclusion, was increased by 21% compared to control conditions
Summary
Pre-eclampsia remains a dominant cause of maternal and fetal mortality in developed countries. VEGF-A165b has been shown to have potent cytoprotective properties in many cell types. We tested the hypothesis that VEGF-A165b may be cytoprotective for placental trophoblasts. Abnormal placental development is central to the pathogenesis of pre-eclampsia. At 10–12 weeks of gestation, trophoblast plugs loosen and oxygenated maternal blood enters the intervillous space, raising the oxygen tension [2]. This stimulates trophoblasts to differentiate into an invasive phenotype, which are less proliferative and more susceptible to apoptosis [3].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
