ANGIOGENESIS AND THE PLACENTAL ENVIRONMENT

Rapid growth and vascularization of the human placenta are characteris tic of early pregnancy and are accomplished in an unusually hypoxic en vironment. Stimulation of placental growth through hypoxia-induced ang iogenesis may therefore be of particular importance. We have previousl y found that several varieties of vascular endothelial growth factor ( VEGF) mRNA, including VEGF(165), are present in cultured placental fib roblasts. We hypothesized that hypoxia mould increase the transcriptio n and translation of VEGF by these cells and provide one mechanism lin king placental development with its environment. Placental fibroblasts were grown in aerobic or anaerobic atmospheric conditions for 72 h. B y 24 h the oxygen tension of the anaerobic culture media was significa ntly less than that of the aerobic cultures. RNA was extracted from th e cells at 24, 48 and 72 h. Following reverse transcription polymerase chain reaction (RT-PCR) stronger signals for VEGF were always found i n the anaerobic cultures and this was confirmed by competitive PCR. mR NA for YEGF(165) was represented most strongly but the anaerobic cultu res also showed clearly mRNA for VEGF(121), VEGF(189) and VEGF(206). T he VEGF protein was also measured in the aerobic and anaerobic culture medium. By 72 h the average concentration of VEGF was significantly h igher (P=0.01) in the anaerobic culture medium. VEGF production is one mechanism through which oxygen supply may influence placental develop ment. Examples of this may include the compensatory placental hypertro phy associated with maternal anaemia and with reproduction at high alt itude.