Some cell types can survive and proliferate when there is very little oxygen around. In humans, cells of the trophoblast - the outermost layer of cells of the blastocyst - do just this, proliferating in 2% O2during the first trimester of pregnancy. But how do such cells sense and respond to low oxygen levels? Armant et al.() turned to the heparin-binding EGF-like growth factor (HBEGF), which is expressed in the placenta during normal pregnancy but is downregulated in pre-eclampsia, a disorder associated with poor trophoblast survival. They found that exposing a human first-trimester trophoblast cell line to 2% O2 caused the upregulation of HBEGF synthesis and secretion, whereas interfering with HBEGF signalling increased apoptosis. The HBEGF receptors HER1 or HER4 were required for this upregulation, indicating that cytotrophoblast survival is maintained by a positive-feedback loop. The authors conclude that low trophoblast survival in pre-eclampsia could be partly due to reduced HBEGF levels, a finding that brings with it new therapeutic possibilities.
