PMID- 24486002
OWN - NLM
STAT- MEDLINE
DCOM- 20141103
LR  - 20140310
IS  - 1879-0054 (Electronic)
IS  - 0739-7240 (Linking)
VI  - 47
DP  - 2014 Apr
TI  - Activation of the CXCL12/CXCR4 signaling axis may drive vascularization of the 
      ovine placenta.
PG  - 11-21
LID - S0739-7240(13)00159-8 [pii]
LID - 10.1016/j.domaniend.2013.12.004 [doi]
AB  - Early pregnancy, when most embryonic losses occur, is a critical period in which 
      vital placental vascularization is established. Vascular endothelial growth 
      factor (VEGF) is a potent inducer of angiogenesis, and factors that regulate VEGF 
      function, expression, or both may ultimately affect vascularization. Activation 
      of the C-X-C chemokine receptor type 4 (CXCR4) by its cognate ligand, C-X-C 
      chemokine ligand 12 (CXCL12), increases VEGF synthesis and secretion, which in 
      turn stimulates CXCL12 and CXCR4 production and this synergistic regulation may 
      influence placental vascularization. We hypothesized that expression of CXCL12, 
      CXCR4, select angiogenic factors, and their receptors would increase in placental 
      tissues during early pregnancy and that treatment of ovine trophectoderm cells 
      with CXCL12 would increase production of angiogenic factors. To test this 
      hypothesis, maternal caruncle (CAR) and fetal extraembryonic membrane (FM) 
      tissues were collected on days 18, 20, 22, 25, 26, and 30 of pregnancy and on day 
      10 of the estrous cycle (control, NP) to determine relative mRNA or protein 
      expression of CXCL12 and CXCR4 and selected angiogenic factors. In CAR, 
      expression of mRNA for CXCR4 increased on day 18, 20, 22, and 25 and CXCL12 
      increased on day 18 and 20 compared with NP ewes. CXCL12 protein followed a 
      similar pattern in CAR tissue, with greater levels on day 20 than in NP tissue. 
      Greater levels of fibroblast growth factor 2 (FGF2) mRNA was observed in CAR on 
      day 20 of gestation than on day 30. In FM, CXCL12, CXCR4, angiopoietin 1, VEGF, 
      and VEGF receptor 1 were enhanced with advancing pregnancy, whereas FGF2 and 
      kinase insert domain receptor (or VEGF receptor 2) peaked on day 25. An increase 
      in protein levels occurred on day 25 compared with day 20 in FM for CXCL12 and 
      CXCR4, as well as a similar tendency for FGF2 protein. Both CXCL12 and CXCR4 are 
      specifically localized to trophoblast cells and to the uterine luminal and 
      glandular epithelium. Treatment of ovine trophectoderm cells with CXCL12 
      increased mRNA expression for VEGF and FGF2. The relationship between VEGF, FGF2, 
      and the CXCL12/CXCR4 signaling underscores the potential role for this chemokine 
      axis in driving placentation.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Quinn, K E
AU  - Quinn KE
AD  - Department of Animal and Range Sciences, New Mexico State University, Las Cruces, 
      NM 88003, USA.
FAU - Ashley, A K
AU  - Ashley AK
AD  - Department of Animal and Range Sciences, New Mexico State University, Las Cruces, 
      NM 88003, USA.
FAU - Reynolds, L P
AU  - Reynolds LP
AD  - Department of Animal Sciences, Center for Nutrition and Pregnancy, North Dakota 
      State University, Fargo, ND 58108, USA.
FAU - Grazul-Bilska, A T
AU  - Grazul-Bilska AT
AD  - Department of Animal Sciences, Center for Nutrition and Pregnancy, North Dakota 
      State University, Fargo, ND 58108, USA.
FAU - Ashley, R L
AU  - Ashley RL
AD  - Department of Animal and Range Sciences, New Mexico State University, Las Cruces, 
      NM 88003, USA. Electronic address: ryashley@nmsu.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20140107
PL  - United States
TA  - Domest Anim Endocrinol
JT  - Domestic animal endocrinology
JID - 8505191
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Receptors, CXCR4)
SB  - IM
MH  - Animals
MH  - Chemokine CXCL12/genetics/*metabolism
MH  - Female
MH  - Gene Expression Regulation/*physiology
MH  - Neovascularization, Physiologic/*physiology
MH  - Placenta/*blood supply
MH  - Pregnancy
MH  - Receptors, CXCR4/genetics/*metabolism
MH  - Sheep/*physiology
OTO - NOTNLM
OT  - CXCL12
OT  - CXCR4
OT  - Pregnancy
OT  - Sheep
OT  - VEGF
OT  - Vascularization
EDAT- 2014/02/04 06:00
MHDA- 2014/11/05 06:00
CRDT- 2014/02/04 06:00
PHST- 2013/09/05 00:00 [received]
PHST- 2013/12/19 00:00 [revised]
PHST- 2013/12/29 00:00 [accepted]
PHST- 2014/02/04 06:00 [entrez]
PHST- 2014/02/04 06:00 [pubmed]
PHST- 2014/11/05 06:00 [medline]
AID - S0739-7240(13)00159-8 [pii]
AID - 10.1016/j.domaniend.2013.12.004 [doi]
PST - ppublish
SO  - Domest Anim Endocrinol. 2014 Apr;47:11-21. doi: 10.1016/j.domaniend.2013.12.004. 
      Epub 2014 Jan 7.