Up-regulation of the endothelin receptor A in placental tissue from first trimester delayed miscarriages.

Objective: This study tested the hypothesis that the endothelin (ET)/ET receptor (ETR) system in biologic fluids and in the human placenta is altered in delayed miscarriages as compared to apparently normal early pregnancies (reference group).

Methods: Immunoreactive ET (irET) concentrations were measured in plasma, urine, and cervical smears from 57 pregnant women in the weeks 6 to 14 of gestation (46 delayed miscarriages, 11 references) with radioimmunoassay (RIA). ET-1, ETR-A, and ETR-B mRNA, and ETR protein expression were measured in placental tissue of 45 early pregnancies (31 delayed miscarriages, 14 references) using semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) and immunoblotting, respectively.

Results: irET levels in plasma, urine, and cervical smears did not differ between groups. Two prevailing ETR-A and ETR-B proteins were found at 45 and 55 kd, and were distributed similarly in delayed miscarriages and references. ETR-A protein and mRNA levels were 54% (P = .009) and threefold (P = .021) higher, respectively, in delayed miscarriages versus references. There was no difference in placental ETR-B and ET-1 mRNA levels between groups.

Conclusion: Neither irET nor ET-1 mRNA levels differ between delayed miscarriages and normal early pregnancies. Pregnancies at risk for miscarriage cannot be identified by measurement of ET in plasma, urine, or cervical smears. Within the ET/ETR system, ETR-A is selectively up-regulated in placental tissue of delayed miscarriages as compared to normal pregnancies. ETR protein processing is similar in both groups.