The Effect of Cigarette Smoke Extract on Trophoblast Cell Viability and Migration: The Role of Adrenomedullin


We tested the hypothesis that cigarette smoke extract (CSE) leads to differences in expression of genes involved in angiogenesis and affects cell viability and migration in a first-trimester cytotrophoblast cell line (HTR-8/SVneo). HTR-8/SVneo cells were treated with 1% CSE, and gene expression for adrenomedullin (ADM), placental growth factor (PIGF), soluble fms-like tyrosine kinase I (sFLT-1), and vascular endothelia growth factor (VEGF) and protein content for ADM, PIGF, and sFlt-1 determined. A cell viability assay and a cell migration scratch assay were utilized following treatment with CSE with and without ADM inhibitor. Adrenomedullin, PIGF, and VEGF gene transcripts were significantly upregulated by 1% CSE treatment compared with unstimulated cells or cells treated with nicotine alone. Neither 1% CSE nor nicotine treatment alone affected sFlt-1 gene expression. There was a significant increase in secreted ADM protein from cells treated with 1% CSE detected by enzyme-linked immuno-sorbant assay, though no differences in PIGF or sFIt-1 production were seen. Treatment with 1 % CSE increased cell viability and cell migration compared with unstimulated cells and was inhibited by co-treatment with ADM inhibitor. Treatment of a first-trimester trophoblast cell line with CSE increases cell viability and cell migration that are reversed by co-treatment with ADM inhibitor, suggesting that ADM at least partially mediates cell growth and viability following CSE treatment.

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Correspondence to Chad A. Grotegut MD.

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Beiswenger, T.R., Feng, L., Brown, H.L. et al. The Effect of Cigarette Smoke Extract on Trophoblast Cell Viability and Migration: The Role of Adrenomedullin. Reprod. Sci. 19, 526–533 (2012).

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  • adrenomedullin
  • angiogenic factors
  • cigarette smoke extract
  • preeclampsia
  • pregnancy
  • tobacco
  • trophoblast