Beyond pregnancy: modulation of trophoblast invasion and its consequences for fetal growth and long-term children's health.

Invasion of extravillous trophoblast cells (EVTs) into the maternal tissues is a key step in the development of a successful pregnancy, excessive and insufficient EVT invasion being associated with pregnancy complications. These pregnancy complications include preeclampsia and fetal growth restriction, both of which are associated with maternal and fetal morbidity and mortality at the time of birth and with increased risk of cardiovascular disease, diabetes and obesity in adult life for infants born from these conditions. In addition, women who develop preeclampsia are also at a greater risk of cardiovascular disease in later life. Many factors, protein and environmental, have been shown to both up- and down-regulate this process in vitro via different mechanisms. The redundancy observed in the regulation of this system suggests that dysregulation of one factor may not contribute to the pathological conditions of EVT invasion and that the relative local concentrations of many different factors may be more important. This review article explores the possibility that the modulation of EVT invasion as a therapeutic target for pregnancies affected by preeclampsia and fetal growth restriction may not be possible or needs to concentrate on the modulation of cell activity as a whole and not of one particular factor.