PMID- 26479247
OWN - NLM
STAT- MEDLINE
DCOM- 20160620
LR  - 20240327
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 10
DP  - 2015
TI  - Leukemia Inhibitory Factor (LIF) Inhibition during Mid-Gestation Impairs 
      Trophoblast Invasion and Spiral Artery Remodelling during Pregnancy in Mice.
PG  - e0129110
LID - 10.1371/journal.pone.0129110 [doi]
LID - e0129110
AB  - The placenta forms the interface between the maternal and fetal circulation and 
      is critical for the establishment of a healthy pregnancy. Trophoblast cell 
      proliferation, migration and invasion into the endometrium are fundamental events 
      in the initiation of placentation. Leukemia inhibitory factor (LIF) has been 
      shown to promote trophoblast invasion in vitro, however its precise role in 
      trophoblast invasion in vivo is unknown. We hypothesized that LIF would be 
      required for normal trophoblast invasion and spiral artery remodeling in mice. 
      Both LIF and its receptor (LIFRalpha) co-localized with cytokeratin-positive invasive 
      endovascular extravillous trophoblasts (EVT) in mouse implantation sites during 
      mid-gestation. Temporally blocking LIF action during specific periods of 
      placental development via administration of our unique LIFRalpha antagonist, PEGLA, 
      resulted in abnormal trophoblast invasion and impaired spiral artery remodeling 
      compared to PEG control. PEGLA-treated mouse decidual vessels were characterized 
      by retention of alpha-smooth muscle actin (alphaSMA)-positive vascular smooth muscle 
      cells (VSMCs), while PEG control decidual vessels were remodelled by 
      cytokeratin-positive trophoblasts. LIF blockade did not alter F4/80-positive 
      decidual macrophage numbers between treatment groups, but resulted in 
      down-regulation of decidual transcript levels of monocyte chemoattractant 
      protein-1 (MCP-1) and interleukin-10 (IL-10), which are important immune cell 
      activation factors that promote spiral artery remodeling during pregnancy. Our 
      data suggest that LIF plays an important role in trophoblast invasion in vivo and 
      may facilitate trophoblast-decidual-immune cell cross talk to enable adequate 
      spiral artery remodeling.
FAU - Winship, Amy
AU  - Winship A
AD  - The Hudson Institute, Melbourne, Australia; Department of Anatomy and 
      Developmental Biology, Monash University, Melbourne, Australia.
FAU - Correia, Jeanne
AU  - Correia J
AD  - The Hudson Institute, Melbourne, Australia.
FAU - Zhang, Jian-Guo
AU  - Zhang JG
AD  - The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; 
      Department of Medical Biology, The University of Melbourne, Melbourne, Australia.
FAU - Nicola, Nicos A
AU  - Nicola NA
AD  - The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; 
      Department of Medical Biology, The University of Melbourne, Melbourne, Australia.
FAU - Dimitriadis, Evdokia
AU  - Dimitriadis E
AD  - The Hudson Institute, Melbourne, Australia; Department of Anatomy and 
      Developmental Biology, Monash University, Melbourne, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151019
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Il6st protein, mouse)
RN  - 0 (Leukemia Inhibitory Factor)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, OSM-LIF)
RN  - 130068-27-8 (Interleukin-10)
RN  - 133483-10-0 (Cytokine Receptor gp130)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
SB  - IM
MH  - Animals
MH  - Arteries/*drug effects/*physiology
MH  - Chemokine CCL2/genetics
MH  - Cytokine Receptor gp130/genetics
MH  - Decidua/blood supply/drug effects
MH  - Embryo Implantation/drug effects
MH  - Female
MH  - Gene Expression Regulation, Developmental/drug effects
MH  - Interleukin-10/genetics
MH  - Leukemia Inhibitory Factor/*antagonists & inhibitors/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Placentation/drug effects
MH  - Polyethylene Glycols/chemistry/pharmacology
MH  - Pregnancy
MH  - Protein Transport/drug effects
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, OSM-LIF/genetics/metabolism
MH  - Trophoblasts/*cytology/*drug effects
MH  - Vascular Remodeling/*drug effects
PMC - PMC4610690
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/10/21 06:00
MHDA- 2016/06/21 06:00
PMCR- 2015/10/19
CRDT- 2015/10/20 06:00
PHST- 2015/03/20 00:00 [received]
PHST- 2015/05/06 00:00 [accepted]
PHST- 2015/10/20 06:00 [entrez]
PHST- 2015/10/21 06:00 [pubmed]
PHST- 2016/06/21 06:00 [medline]
PHST- 2015/10/19 00:00 [pmc-release]
AID - PONE-D-15-11947 [pii]
AID - 10.1371/journal.pone.0129110 [doi]
PST - epublish
SO  - PLoS One. 2015 Oct 19;10(10):e0129110. doi: 10.1371/journal.pone.0129110. 
      eCollection 2015.