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Progesterone, the maternal immune system and the onset of parturition in the mouse.

Authors
  • Edey, Lydia F1
  • Georgiou, Hector1
  • O'Dea, Kieran P2
  • Mesiano, Sam3
  • Herbert, Bronwen R1
  • Lei, Kaiyu1
  • Hua, Renyi1, 3
  • Markovic, Danijela1
  • Waddington, Simon N4
  • MacIntyre, David5
  • Bennett, Philip5
  • Takata, Masao2
  • Johnson, Mark R1
  • 1 Imperial College Parturition Research Group, Academic Department of Obstetrics & Gynaecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, London, UK.
  • 2 Section of Anaesthetics, Pain Medicine, and Intensive Care, Faculty of Medicine, Chelsea and Westminster Hospital, London, UK.
  • 3 Department of Obstetrics and Gynecology, University Hospitals of Cleveland Medical Center, Cleveland, Ohio, USA.
  • 4 The International Peace Maternity & Child Health Hospital of China Welfare Institute (IPMCH), Shanghai, China. , (China)
  • 5 Gene Transfer Technology Group, Institute for Women's Health, University College London, London, UK.
Type
Published Article
Journal
Biology of Reproduction
Publisher
Oxford University Press
Publication Date
Mar 01, 2018
Volume
98
Issue
3
Pages
376–395
Identifiers
DOI: 10.1093/biolre/iox146
PMID: 29145579
Source
Medline
Language
English
License
Unknown

Abstract

The role of progesterone (P4) in the regulation of the local (uterine) and systemic innate immune system, myometrial expression of connexin 43 (Cx-43) and cyclooxygenase 2 (COX-2), and the onset of parturition was examined in (i) naïve mice delivering at term; (ii) E16 mice treated with RU486 (P4-antagonist) to induce preterm parturition; and (iii) in mice treated with P4 to prevent term parturition. In naïve mice, myometrial neutrophil and monocyte numbers peaked at E18 and declined with the onset of parturition. In contrast, circulating monocytes did not change and although neutrophils were increased with pregnancy, they did not change across gestation. The myometrial mRNA and protein levels of most chemokines/cytokines, Cx-43, and COX-2 increased with, but not before, parturition. With RU486-induced parturition, myometrial and systemic neutrophil numbers increased before and myometrial monocyte numbers increased with parturition only. Myometrial chemokine/cytokine mRNA abundance increased with parturition, but protein levels peaked earlier at between 4.5 and 9 h post-RU486. Cx-43, but not COX-2, mRNA expression and protein levels increased prior to the onset of parturition. In mice treated with P4, the gestation-linked increase in myometrial monocyte, but not neutrophil, numbers was prevented, and expression of Cx-43 and COX-2 was reduced. On E20 of P4 supplementation, myometrial chemokine/cytokine and leukocyte numbers, but not Cx-43 and COX-2 expression, increased. These data show that during pregnancy P4 controls myometrial monocyte infiltration, cytokine and prolabor factor synthesis via mRNA-dependent and independent mechanisms and, with prolonged P4 supplementation, P4 action is repressed resulting in increased myometrial inflammation.

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