EXPRESSION OF THE 3 ENDOTHELIN GENES AND PLASMA-LEVELS OF ENDOTHELIN IN PREECLAMPTIC AND NORMAL GESTATIONS

1. Maternal vasoconstriction and fetal growth retardation are part of the syndrome of pre-eclampsia and are thought to be related to placent al insufficiency. There is evidence to suggest that the powerfully vas oactive endothelin peptides might be involved in the pathogenesis. 2. The production of endothelins appears to be regulated mainly by modula tion of mRNA levels, and they are thought to exert their effects local ly, rather than systemically. Hence, the measurement of endothelin mRN A levels in tissues would be expected to reflect the activity of the e ndothelin systems. 3. RNAase protection assays, using specific antisen se probes capable of distinguishing between the endothelin mRNA isofor ms, have been used to examine the expression of the three endothelin g enes in placental villous tissue, amniotic membrane and myometrium. Sa mples were taken from 15 pre-eclamptic women and from 14 women with no rmal gestations. Myometrium was taken at hysterectomy from five non-pr egnant women as an additional control. Plasma concentrations of immuno reactive endothelin [endothelin-1, endothelin-2 and big endothelin (no t distinguished)] were measured in samples taken concurrently from ute rine vein and peripheral blood during surgery in ten patients. 4. The level of endothelin-1 mRNA in placental villous tissue was significant ly higher in pre-eclamptic women (32 weeks gestation) than in control subjects (38 weeks gestation) (1.85 +/- 0.26 versus 0.52 +/- 0.09 arbi trary units, means +/- SEM, P<0.001) and in gravid than in non-gravid myometrium (P<0.001). Endothelin-2 was not expressed in villous tissue , but was expressed in amniotic membrane and myometrium, with relative ly little difference between preeclamptic and control groups. Endothel in-3 was expressed at very low levels in all tissues examined. 5. The concentration of immunoreactive endothelin was higher in uterine than in peripheral vein blood in samples which were taken simultaneously (9 .0 +/- 1.2 versus 5.6 +/- 0.7 pmol/l, P<0.05). Levels were not signifi cantly different in pre-eclamptic and control groups. 6. Endothelin-1 gene expression is increased in placental villous tissue of pre-eclamp tic gestations, possibly contributing to placental vasoconstriction/va scular insufficiency and hence fetal growth retardation in this diseas e.