Activin A and activin receptors in gestational tissue from preeclamptic pregnancies

Maternal serum activin A levels are elevated in women with preeclampsia, To explore whether this could be clue, at least in part, to increased product ion by the gestational tissues, we have measured activin A in the serum of women with (n=23) or without preeclampsia (n=62) at 29-40 weeks of gestatio n and in placenta and fetal membranes from preterm preeclamptic (PT-PE, n=8 ), term preeclamptic (T-PE, n=10) and healthy term controls (T-C, n=10). We have also explored if there are associated changes in activin receptor Alk 2, ActRII and ActRIIB in these tissues. The relative amounts of receptor pr oteins were measured by densitometry on Western blots and receptors and act ivin beta (A) subunit localised by immunohistochemistry in PT-PE, T-PE and T-C gestational tissues (n=8-10/group). Maternal serum activin A levels were significantly elevated in women with p reeclampsia (multiples of the normal median (MoM) = 3.5, P<0.0001, Mann-Whi tney U test) compared with healthy women (median MoM = 1.0). Compared with control tissues, the activin A content was significantly higher in preeclam ptic placentae (P=0.001 and P=0.0005 for PT-PE and T-PE respectively, Mann- Whitney U test), but significantly lower in the amnion (P=0.005 and P=0.014 for PT-PE and T-PE respectively) and choriodecidua (P=0.009 for T-PE). The maternal serum activin A level in women with preeclampsia,vas significantl y correlated with elevated placental production (P=0.01, Pearson's correlat ion). Receptor Alk2 protein levels were significantly elevated it) T-PE pla centae (P=0.0006. Mann-Whitney U test), ActRIIB levels were significantly l ower in PT-PE placentae (P=0.01) and ActRIl levels were significantly lower in PT-PE choriodecidua (P=0.0002) compared with controls. There were no ap parent differences in the distribution of the PA subunit and receptors Alk2 , ActRIl and ActRIIB between control and preeclamptic tissues. These findings suggest that elevated levels of activin A in the maternal ci rculation in association with preeclampsia are due, at least in part, to in creased placental production, and that the regulation of activin synthesis in placenta and fetal membranes is differentially regulated. Further, the d ifferences in activin receptor protein levels between preeclamptic and cont rol placenta and choriodecidua suggest that activin A-induced regulation ma y be altered in preeclampsia.