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Characterization of the adverse effects of nicotine on placental development: in vivo and in vitro studies
- Source :
- AJP-Endocrinology and Metabolism, AJP-Endocrinology and Metabolism, American Physiological Society, 2014, 306 (4), pp.E443-E456. ⟨10.1152/ajpendo.00478.2013⟩, AJP-Endocrinology and Metabolism, 2014, 306 (4), pp.E443-E456. ⟨10.1152/ajpendo.00478.2013⟩
- Publication Year :
- 2014
- Publisher :
- HAL CCSD, 2014.
-
Abstract
- 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 10−9to 10−3M 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.
- Subjects :
- Vascular Endothelial Growth Factor A
medicine.medical_specialty
Nicotine
Physiology
Endocrinology, Diabetes and Metabolism
Placenta
Biology
Cell Line
03 medical and health sciences
endocrine gland-derived vascular endothelial growth factor
0302 clinical medicine
In vivo
Pregnancy
Physiology (medical)
Internal medicine
medicine
Basic Helix-Loop-Helix Transcription Factors
Animals
Rats, Wistar
Adverse effect
030304 developmental biology
Cell Proliferation
0303 health sciences
Fetus
Articles
In vitro
Placentation
3. Good health
Rats
Trophoblasts
Endocrinology
Increased risk
[SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis
In utero
Neonatal outcomes
matrix metalloproteinase 9
Female
nicotinic acetylcholine receptors
rat placentation
trophoblast invasion and differentiation
030217 neurology & neurosurgery
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 01931849 and 15221555
- Database :
- OpenAIRE
- Journal :
- AJP-Endocrinology and Metabolism, AJP-Endocrinology and Metabolism, American Physiological Society, 2014, 306 (4), pp.E443-E456. ⟨10.1152/ajpendo.00478.2013⟩, AJP-Endocrinology and Metabolism, 2014, 306 (4), pp.E443-E456. ⟨10.1152/ajpendo.00478.2013⟩
- Accession number :
- edsair.doi.dedup.....8a535cd3bcd8797b4c34ff9601508f07