The role of adrenomedullin in tubal ectopic pregnancy

Abstract

Adrenomedullin (ADM), a novel vasodilator, exerts diuretic, natriuretic, angiogenic, antioxidative, anti-apoptotic and anti-inflammatory effects in various body systems. It has important regulatory functions in the reproductive system. In the female reproductive tract, ADM was highly expressed in the human and rat oviducts. ADM has been shown to regulate the ciliary beat frequency (CBF) and contractility in the oviduct, affecting the transport of spermatozoa, ova and pre-implantation embryos. The oviduct is the most frequent site of ectopic pregnancy which is an important cause of pregnancy morbidity. In this study, we investigated the role of ADM in tubal ectopic pregnancy (tEP). Oviducts from women undergoing salpingectomy for tEP and those from women undergoing hysterectomy for benign diseases were collected. The latter oviducts served as controls after treatment for 16h with estradiol, progesterone and human chorionic gonadotrophin to simulate the early first trimester hormonal milieu of human pregnancy. ADM expression was studied at the peptide and mRNA levels by immunohistochemistry and RT-PCR respectively. After treatment of the oviducts with ADM and its receptor antagonists, CBF was measured using a photometric method and the contraction of the oviduct was measured using the organ-bath technique. The tEP oviducts expressed significantly less Adm mRNA than the control. The CBF was lower in tEP oviducts and in both groups the CBF increased with graded concentrations (1-100nM) of ADM and were specifically inhibited by a hADM22-52 receptor antagonist. Treatment with ADM increased the basal tone and the frequency of contraction but decreased the amplitude in both the control and tEP groups. Contractility in both groups was not sensitive to the treatment with receptor antagonists. All the results indicate that in the oviduct, the low ADM expression, which may affect the embryo transport through ciliary beat and contraction, may be a causative factor in tubal ectopic pregnancy.