title: Urocortin 2 role in placental and myometrial inflammatory mechanisms at parturition.
abstract: The purpose of the study was to investigate urocortin (Ucn)2 involvement in placental and myometrial inflammatory pathways associated with parturition by evaluating: 1) Ucn2 and its receptor, CRH-receptor type 2 (CRH-R2), expression in laboring/nonlaboring human gestational tissues and in mouse utero-placental tissues approaching delivery; and 2) Ucn2 effect on myometrial contractility and on the expression of inflammatory mediators (prostaglandin F2α receptor and cytokines) and regulation of Ucn2 by TNF-α in cultured myometrial cell line. Placenta (n = 16), fetal membranes (n = 16), and myometrium (n = 22) were obtained from healthy pregnant women delivering at term by vaginal/elective caesarean delivery and from timed-pregnant mice on days 16-19. Expression of Ucn2/CRH-R2 in human/mouse tissues and inflammatory mediators in myometrial cell lines were measured by RT-PCR or ELISA, mouse Ucn2/CRH-R2 protein localization by immunohistochemistry. Ucn2 but not CRH-R2 was up-regulated (P < .05) in all human tissues in labor (compared with before labor) and increased significantly (P < .01) in mouse placenta approaching delivery. Ucn2 was up-regulated by TNF-α via nuclear factor-κB (NF-kB) in myometrium cell lines (P < .05 or P < .01 on the basis of treatment doses) and increased proinflammatory mediators and prostaglandin F (PGF2α) receptor expression (P < .05) via CRH-R2, without a direct effect on contractility. Placental and myometrial Ucn2 may play a role in the endocrine-inflammatory processes of parturition, representing a potential target for treating inflammation-induced obstetric complications.
authors.affiliation: Department of Molecular and Developmental Medicine (C.V., R.N., M.T., F.M.S., F.P.), University of Siena, 53100 Siena, Italy; and Medical Research Council Centre for Reproductive Health (S.B., J.E.N.), University of Edinburgh, EH16 4TY Edinburgh, United Kingdom.
authors.forename: Chiara
authors.initials: C
authors.lastname: Voltolini
authors.forename: Sharon
authors.initials: S
authors.lastname: Battersby
authors.forename: Romina
authors.initials: R
authors.lastname: Novembri
authors.forename: Michela
authors.initials: M
authors.lastname: Torricelli
authors.forename: Filiberto M
authors.initials: FM
authors.lastname: Severi
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
authors.forename: Jane E
authors.initials: JE
authors.lastname: Norman
mesh_terms: D000818:Animals; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007743:Labor, Obstetric / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009215:Myometrium / Q000502:physiology*; D016328:NF-kappa B; D036801:Parturition / Q000276:immunology / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha; D054832:Urocortins / Q000378:metabolism*; D014590:Uterine Contraction
chemical_list: C101531:CRF receptor type 2; D016207:Cytokines; D016328:NF-kappa B; D018019:Receptors, Corticotropin-Releasing Hormone; D011982:Receptors, Prostaglandin; D014409:Tumor Necrosis Factor-alpha; C426705:UCN2 protein, human; D054832:Urocortins; C034671:prostaglandin F2alpha receptor; C518358:urocortin 2, mouse; D003346:Corticotropin-Releasing Hormone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human