Possible Role of Adrenomedullin In the Pathogenesis of Tubal Ectopic Pregnancy

Context: Tubal ectopic pregnancy (tEP) is currently the leading cause of pregnancy-related deaths during the first trimester. Our current knowledge on the molecular pathogenesis is limited. Objective: The objective of the study was to find out the possible role of adrenomedullin (ADM) in the pathogenesis of tEP. Design: This was an experimental in vitro study on oviductal tissue. Setting: The study was conducted at a university teaching hospital. Patients and Interventions: Patients included those having oviducts removed surgically during salpingectomy for tEP or hysterectomy for benign gynecological conditions. Oviductal tissues were incubated in hormonal condition mimicking early pregnancy before used for in vitro experiments. Main Outcome Measures: Plasma ADM concentration, oviductal expression of ADM and its receptors, ciliary beat frequency, smooth muscle contraction were measured. Results: The ciliary beat frequency and frequency of muscle contraction were lower in the oviducts from patients with tEP than those from simulated normal pregnancy. The plasma and oviductal tissue ADM levels were also lower. The decreases in ciliary beat and frequency of contraction were restored to normal after ADM treatment. Conclusions: The results suggest that the lower ADM level in the oviducts of tEP may lead to the decrease in ciliary beating and muscle contraction, with the result that the embryo is retained and implanted in the oviduct. Our findings explain for the first time the etiology of tubal pregnancy on the basis of an impairment of the transport of the fertilized ovum resulting from an ADM deficiency and raise the possibility of using the plasma ADM level as a predictor for tubal ectopic pregnancy. ( J Clin Endocrinol Metab 97: 2105-2112, 2012)