Cigarette smoke induces oxidative stress and apoptosis in normal term fetal membranes

Ramkumar Menon, S. J. Fortunato, J. Yu, G. L. Milne, S. Sanchez, C. O. Drobek, M. Lappas, R. N. Taylor

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Cigarette smoking and bacterial infections are two major risk factors associated with preterm prelabor rupture of membranes (pPROM). We hypothesized that exposure of fetal membranes to cigarette smoke extracts might induce oxidative stress (OS) and fetal membrane apoptosis, culminating in an alternate pathway to that commonly activated by infection. To test this, we characterized the production of prostanoids and biomarkers of apoptosis in normal term human fetal membrane explant cultures. Fetal membrane explants collected at term (from cesarean deliveries, not in labor) were stimulated with cigarette smoke extract (CSE) for 24 h. Two classes of prostanoids, F2-Isoprostane (F2-IsoP), a marker of OS and PGF2α, a classical uterotonin, were measured by gas chromatography/mass spectrometry. Western blot analyses of tissue lysates were performed to quantify the anti-apoptotic protein Bcl2 and actin (as a control). Fetal membrane apoptosis was detected by immunohistochemistry for active caspase 3 and confirmed by TUNEL staining for nuclear fragmentation. CSE exposure resulted in significantly more F2-IsoP production from fetal membranes (242.8 ± 79.3 pg/ml/mg of total membrane protein) compared to unstimulated controls (131.5 ± 53.1 pg/ml/mg; p < 0.0001). By contrast, PGF2α was not different in CSE vs. controls (1083 ± 527 vs. 1136 ± 835 pg/ml/mg of protein; p = 0.80). CSE-exposed tissues demonstrated a dose-dependent decrease in Bcl2 expression and increases in active caspase 3 and nuclear fragmentation in both amnion and chorion cells compared to controls. In summary, fetal membranes exposed to CSE manifest evidence of OS and apoptosis. The differential pattern of prostanoid production observed in this study supports the hypothesis that an alternate non-inflammatory pathway mediated by OS and apoptosis in pPROM may promote proteolysis resulting in membrane weakening and rupture.

Original languageEnglish (US)
Pages (from-to)317-322
Number of pages6
JournalPlacenta
Volume32
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

Fingerprint

Extraembryonic Membranes
Smoke
Tobacco Products
Oxidative Stress
Apoptosis
Prostaglandins
Rupture
Dinoprost
Caspase 3
Membranes
F2-Isoprostanes
Chorion
Apoptosis Regulatory Proteins
Amnion
Tissue Extracts
In Situ Nick-End Labeling
Bacterial Infections
Gas Chromatography-Mass Spectrometry
Proteolysis
Actins

Keywords

  • Amniochorion
  • Inflammation
  • Isoprostanes
  • pPROM
  • Prematurity
  • Preterm birth
  • Risk factors

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine
  • Developmental Biology

Cite this

Menon, R., Fortunato, S. J., Yu, J., Milne, G. L., Sanchez, S., Drobek, C. O., ... Taylor, R. N. (2011). Cigarette smoke induces oxidative stress and apoptosis in normal term fetal membranes. Placenta, 32(4), 317-322. https://doi.org/10.1016/j.placenta.2011.01.015

Cigarette smoke induces oxidative stress and apoptosis in normal term fetal membranes. / Menon, Ramkumar; Fortunato, S. J.; Yu, J.; Milne, G. L.; Sanchez, S.; Drobek, C. O.; Lappas, M.; Taylor, R. N.

In: Placenta, Vol. 32, No. 4, 04.2011, p. 317-322.

Research output: Contribution to journalArticle

Menon, R, Fortunato, SJ, Yu, J, Milne, GL, Sanchez, S, Drobek, CO, Lappas, M & Taylor, RN 2011, 'Cigarette smoke induces oxidative stress and apoptosis in normal term fetal membranes', Placenta, vol. 32, no. 4, pp. 317-322. https://doi.org/10.1016/j.placenta.2011.01.015
Menon, Ramkumar ; Fortunato, S. J. ; Yu, J. ; Milne, G. L. ; Sanchez, S. ; Drobek, C. O. ; Lappas, M. ; Taylor, R. N. / Cigarette smoke induces oxidative stress and apoptosis in normal term fetal membranes. In: Placenta. 2011 ; Vol. 32, No. 4. pp. 317-322.
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