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 journalArticle (Academic Journal)peer-review

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.

Original languageEnglish
Pages (from-to)670-9
Number of pages10
JournalEndocrinology
Volume156
Issue number2
DOIs
Publication statusPublished - Feb 2015

Keywords

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

Fingerprint Dive into the research topics of 'Urocortin 2 role in placental and myometrial inflammatory mechanisms at parturition'. Together they form a unique fingerprint.

Cite this