Overproduction of the follistatin-related gene protein in the placenta and maternal serum of women with pre-eclampsia

Objective: To characterise the follistatin-related gene (FLRG) in pre-eclampsia, one of the differentially expressed genes in pre-eclamptic placenta. Design and methods: We examined and compared the messenger RNA (mRNA) and protein levels of FLRG in placentas and maternal sera from women with uncomplicated pregnancy, and those with pre-eclampsia using real-time reverse transcription polymerase chain reaction, Western blot, immunohistochemistry, and enzyme-linked immunosorbent assay. Setting: Antenatal clinics in a teaching hospital. Population: Women with uncomplicated pregnancy (n = 21) and those with pre-eclampsia (n = 21). Results: FLRG mRNA is overexpressed in pre-eclamptic placental tissues (P < 0.01). Upregulated FLRG protein consists of both an immature 28-kDa cellular product and a mature 33-kDa secretory form, which are differentially glycosylated. FLRG is normally produced at its highest levels in endothelial cells and at moderate amounts in syncytiotrophoblast cells, but in pre-eclampsia, the syncytiotrophoblast FLRG levels are dramatically increased. We also determined the maternal serum concentrations of FLRG in our uncomplicated pregnancy subjects and in our pre-eclamptic groups, and found that they are significantly elevated in pre-eclampsia in a similar manner to activin A and inhibin A. However, the increase in FLRG in these cases is independent of activin A or inhibin A, and is associated with low-birthweight outcomes. Conclusion: Our current data show the placental and secretory changes of FLRG protein in pre-eclampsia, and also indicate the potential usefulness of FLRG as an additional diagnostic marker for pre-eclampsia.