Cigarette smoke condensate affects the retinoid pathway in human amnion

Placenta. 2017 Oct:58:98-104. doi: 10.1016/j.placenta.2017.08.076. Epub 2017 Sep 1.


Introduction: The preterm premature rupture of membranes (PPROM) is a frequent pathology responsible of more than 30% of preterm births. Tobacco smoking is one of the most frequently described risk factors identified and contributes to the pre term weakening of fetal membranes. As previously demonstrated, all-trans retinoic acid (atRA) regulates several genes involved in the extracellular matrix dynamics, an essential actor in fetal membrane ruptures. We hypothesized that cigarette smoke may affect this pathway in human amnion.

Methods: Amnion was obtained from full-term fetal membranes collected from non-smoking women after cesarean births and used either as explants or for the isolation of derived epithelial cells. The pro-healing and transcriptomic effects of atRA were studied by a scratch assay experiment and quantitative RT-PCR, respectively, after treatment with dimethyl sulfoxyde (DMSO), atRA, DMSO + cigarette smoke condensate (CSC), or atRA + CSC.

Results: Our results show a strong alteration of the retinoid pathway after CSC treatment on amnion-derived epithelial cells and explants. We first demonstrated that CSC inhibits the activity of the RARE reporter gene in amnion-derived epithelial cells. Then, atRA's effects on both the transcription of its target genes and wound healing were demonstrated to be inhibited or at least decreased by the CSC in human amnion epithelial cells.

Discussion: Here, we demonstrated that CSC altered the retinoid signal, already known to have roles in fetal membrane physiopathology. These results highlight a potential negative action of maternal smoking on the retinoid pathway in human amnion and more generally on pregnancy.

Keywords: Extracellular matrix; Fetal membranes; Maternal smoking; Retinoid.

MeSH terms

  • Amnion / drug effects*
  • Amnion / metabolism
  • Cigarette Smoking / adverse effects*
  • Female
  • Fetal Membranes, Premature Rupture / etiology*
  • Fetal Membranes, Premature Rupture / metabolism
  • Humans
  • Pregnancy
  • Retinoids / metabolism*
  • Signal Transduction / drug effects*
  • Smoke / adverse effects*


  • Retinoids
  • Smoke