Infiltration of myeloid cells into decidua is a critical early event in the labour cascade and post-partum uterine remodelling

J Cell Mol Med. 2013 Feb;17(2):311-24. doi: 10.1111/jcmm.12012. Epub 2013 Feb 5.

Abstract

Leucocyte infiltration in the decidua (maternal-foetal interface) before, during and after term (TL) and preterm labour (PTL) was studied in mouse. We also investigated the mechanism of peripheral leucocyte recruitment into decidua by analysing the tissue cytokine profiles. Decidual tissues were collected during late gestation, TL and post-partum (PP). PTL was initiated on gestational day 15 by intrauterine injection of Lipopolysaccharide (LPS, 125 μg) or progesterone signalling antagonism by RU486. Animals were killed during PTL or PP. Decidua basalis was analysed using FACS and immunohistochemistry. Markers of myeloid cell differentiation (Gr1, Ly6G, Neu7/4, F4/80) were assessed to define tissue monocytes (M), neutrophils (N) and macrophages (Macs). Flow cytometry revealed a significant (P < 0.05) increase in decidual Macs prior to TL; M and N numbers increased during TL and further increased during PP, which correlated with immunohistochemistry data. Massive influx of N, but not Macs and M, was detected by FACS during LPS-PTL (P < 0.05) but not RU486-PTL. Highest levels of N infiltration into the decidua occurred PP in both LPS and RU486 groups. Decidual infiltration during TL and RU486-PTL was accompanied by an increase in pro-inflammatory cytokines (IL1b and IL6) and CCL2 chemokine; LPS-PTL showed increases in multiple cytokines. PP period following TL and PTL was associated with further up-regulation of multiple cytokines/chemokines (P < 0.05). Our data suggest a programme of myeloid cells involvement in parturition with the pre-partum influx of Macs into the decidua contributing to the progression of labour, whereas the later influx of M and N contribute to PP decidual involution.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Chemokines / genetics
  • Chemokines / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Decidua / physiology*
  • Female
  • Flow Cytometry
  • Hormone Antagonists / pharmacology
  • Immunoenzyme Techniques
  • Leukocytes / cytology
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Lipopolysaccharides / administration & dosage
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mifepristone / pharmacology
  • Myeloid Cells / cytology*
  • Myeloid Cells / drug effects
  • Myeloid Cells / metabolism
  • Obstetric Labor, Premature / metabolism*
  • Postpartum Period / physiology*
  • Pregnancy
  • Pregnancy, Animal*
  • Progesterone / administration & dosage
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Uterus / physiology*

Substances

  • Chemokines
  • Cytokines
  • Hormone Antagonists
  • Lipopolysaccharides
  • RNA, Messenger
  • Mifepristone
  • Progesterone