Activation of the CXCL12/CXCR4 signaling axis may drive vascularization of the ovine placenta

Quinn, Kelsey E.; Ashley, Amanda K.; Reynolds, Lawrence P.; Grazul-Bilska, Anna T.; Ashley, Ryan L.

doi:10.1016/j.domaniend.2013.12.004

Cited by 35 publications

(36 citation statements)

References 38 publications

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“…Other studies using in vitro and in vivo systems proved that CXCL12/CXCR4 signaling is associated with elevated levels of VEGF and VEGF-induced vascularization [74,77]. Notably, elevated VEGF expression induced by challenge with CXCL12 could, in turn, promote production of CXCL12 as well as CXCR4, implying the important role of the synergistic regulation of these chemokines in placental vascularization [11,78] (Fig. 2).…”

Section: Cxcl12-mediated Signaling In Placentamentioning

confidence: 83%

“…Moreover, interstitial trophoblasts may also aggregate and partly fuse to form placental bed giant cells which are considered to be the end-stage of EVT differentiation [22]. It has been proved that the CXCL12/CXCR4 axis plays an important role in the differentiation of cytotrophoblast progenitor cells into various trophoblast subtypes [11,12,48]. However, dysregulation of CXCL12 and CXCR4 may lead to aberrant early trophoblast differentiation and invasion, consequently resulting in pathological placentation [54].…”

Section: Cxcl12-mediated Signaling In Trophoblast Differentiationmentioning

confidence: 99%

“…There is a close link between the chemokine CXCL12 and pro-angiogenic factors including VEGF, PLGF, FGF-2, angiopoietin-1, and insulin-like growth factor during placental angiogenesis [11,73,74]. Of these angiogenic factors, VEGF is generally considered as a potent inducer of angiogenesis.…”

Section: Cxcl12-mediated Signaling In Placentamentioning

confidence: 99%

“…In addition, the CXCL12/CXCR4 axis has also a significant relationship with other angiogenic factors. For instance, treatment of ovine trophectoderm cells with CXCL12 increased Fgf-2 mRNA expression, which promoted placental vascularity and neo-angiogenesis during placentation [11]. CXCL12 can also promote the expressions of angiopoietin-1, PLGF, and insulin-like growth factor to enhance the recruitment of endothelial progenitor cells into areas of placental vascularization via binding to CXCR4 [11,73].…”

Section: Cxcl12-mediated Signaling In Placentamentioning

confidence: 99%

“…CXCL12 and its receptors including CXCR4 and CXCR7 are diffusely expressed in human placental tissue and are associated with several crucial reproductive biology processes such as placentation, implantation, and embryogenesis, as well as materno-fetal immune tolerance and vascular remodeling during early pregnancy [8][9][10][11]. By binding to CXCR4, CXCL12 can promote trophoblast-directed invasion into the maternal endometrium and induce placental angiogenesis [12].…”

Section: Introductionmentioning

confidence: 99%

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Insights into the mechanism of CXCL12-mediated signaling in trophoblast functions and placental angiogenesis

Wang¹,

Li²,

Zhao³

et al. 2015

ABBS

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The chemokine CXCL12 and its receptor CXCR4 are important signaling components required for human blastocyst implantation and the progression of pregnancy. Growing evidence indicates that the CXCL12/CXCR4 axis can regulate trophoblast function and uterine spiral artery remodeling, which plays a fundamental role in placentation and fetal outcome. The orphan receptor CXCR7 is also believed to partly regulate the function of the CXCL12/CXCR4 axis. Additionally, the CXCL12/ CXCR4/CXCR7 axis can enhance the cross-talk between trophoblasts and decidual cells such as uterine natural killer cells and decidual stromal cells which are involved in regulation of trophoblast differentiation and invasion and placental angiogenesis. In addition, recent studies proved that CXCL12 expression is elevated in the placenta and mid-trimester amniotic fluid of pregnant women with preeclampsia, implying that dysregulation of CXCL12 plays a role in the pathogenesis of preeclampsia. Further understanding of the regulatory mechanisms of CXCL12-mediated signaling in trophoblast functions and placental angiogenesis may help to design novel therapeutic approaches for pregnancy-associated diseases.

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Section: Cxcl12-mediated Signaling In Placentamentioning

confidence: 83%

Section: Cxcl12-mediated Signaling In Trophoblast Differentiationmentioning

confidence: 99%

Section: Cxcl12-mediated Signaling In Placentamentioning

confidence: 99%

Section: Cxcl12-mediated Signaling In Placentamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Insights into the mechanism of CXCL12-mediated signaling in trophoblast functions and placental angiogenesis

Wang¹,

Li²,

Zhao³

et al. 2015

ABBS

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Effect of Placental Growth Factor on Trophoblast–Endothelial Cell Interactions In Vitro

Chau

Hennessy

et al. 2020

Reprod. Sci.

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CXCL12 May Drive Inflammatory Potential in the Ovine Corpus Luteum During Implantation

2021

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Adequate corpus luteum (CL) function is paramount to successful pregnancy. Structural and functional CL integrity is controlled by diverse cell types that contribute and respond to the local cytokine milieu. The chemokine ligand 12 (CXCL12) and receptor, CXCR4, are modulators of inflammation and cell survival, but little is understood about CXCL12-CXCR4 axis and CL functional regulation. Corpora lutea from control nonpregnant ewes (n = 5; day 10 estrous cycle (D10C)) and pregnant ewes (n = 5/day) on days 20 (D20P) and 30 (D30P) post-breeding were analyzed for gene and protein expression of CXCL12, CXCR4, and select inflammatory cytokines. In separate cell culture studies, cytokine production was evaluated following CXCL12 treatment. Abundance of CXCL12 and CXCR4 increased (P < 0.05) in pregnant ewes compared to nonpregnant ewes, as determined by a combination of quantitative PCR, immunoblot, and immunofluorescence microscopy. CXCR4 was detected in steroidogenic and nonsteroidogenic cells in ovine CL, and select pro-inflammatory mediators were greater in CL from pregnant ewes. In vitro studies revealed greater abundance of tumor necrosis factor (TNF) following CXCL12 administration (P = 0.05), while P4 levels in cell media were unchanged. Fully functional CL of pregnant ewes is characterized by increased abundance of inflammatory cytokines which may function in a luteotropic manner. We report concurrent increases in CXCL12, CXCR4, and select inflammatory mediators in ovine CL as early pregnancy progresses. We propose CXCL12 stimulates production of select cytokines, rather than P4 in the CL to assist in CL establishment and survival.

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Activation of the CXCL12/CXCR4 signaling axis may drive vascularization of the ovine placenta

Cited by 35 publications

References 38 publications

Insights into the mechanism of CXCL12-mediated signaling in trophoblast functions and placental angiogenesis

Insights into the mechanism of CXCL12-mediated signaling in trophoblast functions and placental angiogenesis

Effect of Placental Growth Factor on Trophoblast–Endothelial Cell Interactions In Vitro

CXCL12 May Drive Inflammatory Potential in the Ovine Corpus Luteum During Implantation

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