Expression of Adrenomedullin in Human Oviduct, Its Regulation by the Hormonal Cycle and Contact with Spermatozoa, And Its Effect on Ciliary Beat Frequency of the Oviductal Epithelium

Abstract

Abstract Context: Adrenomedullin (ADM) has been found expressed in the mouse oviduct and might play a role in reproduction. Objective: To demonstrate the expression of adrenomedullin (ADM) in the human oviduct, investigate its regulation by steroidal hormones and spermatozoa contact, and study its effect on ciliary beat frequency (CBF) in the human oviduct. Design, Setting, Patients and Interventions: Oviducts from women undergoing hysterectomy for benign diseases in a university hospital were collected. The oviducts were treated with estradiol and/or progesterone to simulate different phases of the ovarian cycle. ADM expression was studied at the peptide and mRNA levels by immunohistochemistry and RT-PCR respectively. CBF was measured after treatment with graded concentrations of ADM and its antagonists. Cells from OE-E6/E7, an immortalized oviductal cell line, as well as oviductal tissue were co-cultured with and without direct contact with capacitated human spermatozoa to compare oviductal cell ADM expression levels. CBF was also analyzed in oviductal tissue after spermatozoa-oviduct co-incubation. Results: ADM expression was the highest in the isthmic region and in a hormonal environment simulating the early luteal phase. CBF was increased by ADM in a dose-dependent manner which was blocked by ADM and calcitonin-gene-related peptide receptor antagonists. Direct contact with spermatozoa in co-culture resulted in higher ADM expression in OE-E6/E7 cell line and oviductal tissue, and higher CBF in oviductal epithelium. Conclusions: ADM expression in the human oviduct is hormone-dependent and is up-regulated by sperm contact. ADM stimulates ciliary motility of the human oviduct.