PMID- 24368670
OWN - NLM
STAT- MEDLINE
DCOM- 20140408
LR  - 20211021
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 306
IP  - 4
DP  - 2014 Feb 15
TI  - Characterization of the adverse effects of nicotine on placental development: in 
      vivo and in vitro studies.
PG  - E443-56
LID - 10.1152/ajpendo.00478.2013 [doi]
AB  - In utero exposure to nicotine is associated with increased risk of numerous 
      adverse fetal and neonatal outcomes, which suggests that it acts directly to 
      affect placental development and the establishment of the fetomaternal 
      circulation (FC). This study used both in vivo [Wistar rats treated with 1 mg/kg 
      nicotine from 2 wk prior to mating until gestational day (GD) 15] and in vitro 
      (RCHO-1 cell line; treated with 10(-9) to 10(-3)M nicotine) models to examine the 
      effects of nicotine on these pathways. At GD 15, control and treated placentas 
      were examined for the impact of nicotine on 1) trophoblast invasion, 
      proliferation, and degree of hypoxia, 2) labyrinth vascularization, 3) expression 
      of key genes of placental development, and 4) expression of placental angiogenic 
      factors. The RCHO-1 cell line was used to determine the direct effects of 
      nicotine on trophoblast differentiation. Our in vivo experiments show that 
      nicotine inhibits trophoblast interstitial invasion, increases placental hypoxia, 
      downregulates labyrinth vascularization as well as key transcription factors 
      Hand1 and GCM1, and decreases local and circulating EG-VEGF, a key placental 
      angiogenic factor. The in vitro experiments confirmed the inhibitory effects of 
      nicotine on the trophoblast migration, invasion, and differentiation processes 
      and demonstrated that those effects are most likely due to a dysregulation in the 
      expression of nicotine receptors and a decrease in MMP9 activity. Taken together, 
      these data suggest that adverse effects of maternal smoking on pregnancy outcome 
      are due in part to direct and endocrine effects of nicotine on the main processes 
      of placental development and establishment of FC.
FAU - Holloway, A C
AU  - Holloway AC
AD  - Centre National de la Recherche Scientifique, Grenoble, France;
FAU - Salomon, A
AU  - Salomon A
FAU - Soares, M J
AU  - Soares MJ
FAU - Garnier, V
AU  - Garnier V
FAU - Raha, S
AU  - Raha S
FAU - Sergent, F
AU  - Sergent F
FAU - Nicholson, C J
AU  - Nicholson CJ
FAU - Feige, J J
AU  - Feige JJ
FAU - Benharouga, M
AU  - Benharouga M
FAU - Alfaidy, N
AU  - Alfaidy N
LA  - eng
GR  - R01 HD020676/HD/NICHD NIH HHS/United States
GR  - FRN 94331/CAPMC/CIHR/Canada
GR  - MOP 86474/CAPMC/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131224
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (helix-loop-helix protein, eHAND)
RN  - 6M3C89ZY6R (Nicotine)
SB  - IM
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors/metabolism
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Female
MH  - Nicotine/*pharmacology
MH  - Placenta/*drug effects/metabolism
MH  - Placentation/*drug effects
MH  - Pregnancy
MH  - Rats
MH  - Rats, Wistar
MH  - Trophoblasts/cytology/*drug effects/metabolism
MH  - Vascular Endothelial Growth Factor A/metabolism
PMC - PMC4865199
OTO - NOTNLM
OT  - endocrine gland-derived vascular endothelial growth factor
OT  - matrix metalloproteinase 9
OT  - nicotinic acetylcholine receptors
OT  - rat placentation
OT  - trophoblast invasion and differentiation
EDAT- 2013/12/26 06:00
MHDA- 2014/04/09 06:00
PMCR- 2015/02/15
CRDT- 2013/12/26 06:00
PHST- 2013/12/26 06:00 [entrez]
PHST- 2013/12/26 06:00 [pubmed]
PHST- 2014/04/09 06:00 [medline]
PHST- 2015/02/15 00:00 [pmc-release]
AID - ajpendo.00478.2013 [pii]
AID - E-00478-2013 [pii]
AID - 10.1152/ajpendo.00478.2013 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2014 Feb 15;306(4):E443-56. doi: 
      10.1152/ajpendo.00478.2013. Epub 2013 Dec 24.