Urocortin 2 role in placental and myometrial inflammatory mechanisms at parturition

Chiara Voltolini, Sharon Battersby, Romina Novembri, Michela Torricelli, Filiberto M Severi, Felice Petraglia, Jane E Norman

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)670-9
Number of pages10
Issue number2
Early online date26 Nov 2014
Publication statusPublished - Feb 2015


  • Animals
  • Cell Line
  • Corticotropin-Releasing Hormone
  • Cyclooxygenase 2
  • Cytokines
  • Female
  • Humans
  • Labor, Obstetric
  • Mice
  • Myometrium
  • NF-kappa B
  • Parturition
  • Placenta
  • Pregnancy
  • Receptors, Corticotropin-Releasing Hormone
  • Receptors, Prostaglandin
  • Tumor Necrosis Factor-alpha
  • Urocortins
  • Uterine Contraction


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