PMID- 37724932
OWN - NLM
STAT- MEDLINE
DCOM- 20231218
LR  - 20240210
IS  - 1529-7268 (Electronic)
IS  - 0006-3363 (Print)
IS  - 0006-3363 (Linking)
VI  - 109
IP  - 6
DP  - 2023 Dec 11
TI  - Placental insufficiency and heavier placentas in sheep after suppressing 
      CXCL12/CXCR4 signaling during implantationdagger.
PG  - 982-993
LID - 10.1093/biolre/ioad122 [doi]
AB  - During implantation, trophoblast cell invasion and differentiation is 
      predominantly important to achieving proper placental formation and embryonic 
      development. The chemokine, C-X-C motif chemokine ligand 12 (CXCL12) working 
      through its receptor C-X-C motif chemokine receptor 4 (CXCR4) is implicated in 
      implantation and placentation but precise roles of this axis are unclear. 
      Suppressing CXCL12/CXCR4 signaling at the fetal-maternal interface in sheep 
      reduces trophoblast invasion, disrupts uterine remodeling, and diminishes 
      placental vascularization. We hypothesize these negative impacts during 
      implantation will manifest as compromised fetal and placental growth at 
      midgestation. To test, on day 12 postbreeding, osmotic pumps were surgically 
      installed in 30 ewes and delivered intrauterine CXCR4 inhibitor or saline for 7 
      or 14 days. On day 90, fetal/maternal tissues were collected, measured, weighed, 
      and maternal (caruncle) and fetal (cotyledon) placenta components separated and 
      analyzed. The objectives were to determine if (i) suppressing CXCL12/CXCR4 during 
      implantation results in reduced fetal and placental growth and development and 
      (ii) if varying the amount of time CXCL12/CXCR4 is suppressed impacts 
      fetal/placental development. Fetal weights were similar; however greater 
      placental weight and placentome numbers occurred when CXCL12/CXCR4 was suppressed 
      for 14 days. In caruncles, greater abundance of fibroblast growth factor 2, 
      vascular endothelial growth factor A, vascular endothelial growth factor A 
      receptor 1 (FLT-1), and placental growth factor were observed after suppressing 
      CXCL12/CXCR4. Similar results occurred in cotyledons except less vascular 
      endothelial growth factor in 7 day group and less fibroblast growth factor in 
      14 day group. Our data underscore the importance of CXCL12/CXCR4 signaling during 
      placentation and provide strong evidence that altering CXCL12-mediated signaling 
      induces enduring placental effects manifesting later in gestation.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of Society 
      for the Study of Reproduction. All rights reserved. For permissions, please 
      e-mail: journals.permissions@oup.com.
FAU - Ashley, Ryan L
AU  - Ashley RL
AD  - Department of Animal and Range Sciences, New Mexico State University, Las Cruces, 
      NM, USA.
FAU - Trigo, Elisa M
AU  - Trigo EM
AD  - Department of Animal and Range Sciences, New Mexico State University, Las Cruces, 
      NM, USA.
FAU - Ervin, Jacqueline M
AU  - Ervin JM
AD  - Department of Animal and Range Sciences, New Mexico State University, Las Cruces, 
      NM, USA.
LA  - eng
GR  - SC1 GM139712/GM/NIGMS NIH HHS/United States
GR  - 1SC1GM139712-01/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 144589-93-5 (Placenta Growth Factor)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (CXCL12 protein, human)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (Receptors, CXCR4)
SB  - IM
MH  - Humans
MH  - Pregnancy
MH  - Female
MH  - Sheep
MH  - Animals
MH  - *Placenta/metabolism
MH  - Vascular Endothelial Growth Factor A/metabolism
MH  - *Placental Insufficiency/metabolism
MH  - Placenta Growth Factor/metabolism
MH  - Placentation
MH  - Chemokine CXCL12/metabolism
MH  - Receptors, CXCR4/genetics/metabolism
PMC - PMC10724462
OTO - NOTNLM
OT  - CXCL12
OT  - CXCR4
OT  - PLGF
OT  - VEGF
OT  - caruncle
OT  - cotyledon
OT  - placental insufficiency
OT  - preeclampsia
OT  - sheep
OT  - trophoblast
EDAT- 2023/09/19 17:43
MHDA- 2023/12/18 06:41
PMCR- 2024/09/19
CRDT- 2023/09/19 09:42
PHST- 2023/06/08 00:00 [received]
PHST- 2023/08/28 00:00 [revised]
PHST- 2023/09/15 00:00 [accepted]
PHST- 2024/09/19 00:00 [pmc-release]
PHST- 2023/12/18 06:41 [medline]
PHST- 2023/09/19 17:43 [pubmed]
PHST- 2023/09/19 09:42 [entrez]
AID - 7277130 [pii]
AID - ioad122 [pii]
AID - 10.1093/biolre/ioad122 [doi]
PST - ppublish
SO  - Biol Reprod. 2023 Dec 11;109(6):982-993. doi: 10.1093/biolre/ioad122.