title: Smoking during pregnancy causes double-strand DNA break damage to the placenta.
abstract: Despite the adverse effects of smoking, many pregnancies are exposed to tobacco smoke. Recent studies have investigated whether smoking damages placental DNA by measuring DNA adducts. This study investigated whether a more severe lesion, double-strand DNA breaks, was also present in the tobacco smoking-exposed placenta. Term placentae from women who smoked during their entire pregnancies (n = 52), from those who had ceased smoking for at least 4 weeks before delivery (previous smokers, n = 34), and from nonsmoking women (n = 150) were examined using the DNA double-strand break marker phosphorylated γ H2AX. The extent of DNA damage was assessed according to cell type and additional markers were applied for cell fate (apoptosis and DNA repair), and function (human chorionic gonadotropin, human placental lactogen, and glucose transporter 1), to characterize the effect of the DNA damage on placental integrity. Marked phosphorylated γ H2AX-positive cells occurred in the villous syncytiotrophoblast and syncytial knot nuclei in placentae from smokers (P < .001). Phosphorylated γ H2AX foci did not colocalize with the DNA repair protein 53BP1, and damaged nuclei had a marked reduction in expression of human chorionic gonadotropin, human placental lactogen, and glucose transporter 1. Minimal DNA damage, similar to nonsmokers, was present in previous smokers including those that had ceased smoking for just over 4 weeks before delivery. In summary, smoking during pregnancy was associated with marked double-strand DNA break damage to the syncytiotrophoblast. We suggest that smoking cessation is important to prevent additional DNA damage and to facilitate DNA repair.
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand. Electronic address: tania.slatter@otago.ac.nz.
authors.forename: Tania L
authors.initials: TL
authors.lastname: Slatter
authors.forename: Lydia
authors.initials: L
authors.lastname: Park
authors.forename: Karyn
authors.initials: K
authors.lastname: Anderson
authors.forename: Viwa
authors.initials: V
authors.lastname: Lailai-Tasmania
authors.forename: Peter
authors.initials: P
authors.lastname: Herbison
authors.forename: William
authors.initials: W
authors.lastname: Clow
authors.forename: Janice A
authors.initials: JA
authors.lastname: Royds
authors.forename: Celia
authors.initials: C
authors.lastname: Devenish
authors.forename: Noelyn A
authors.initials: NA
authors.lastname: Hung
mesh_terms: D053903:DNA Breaks, Double-Stranded; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D010920:Placenta / Q000473:pathology*; D011247:Pregnancy; D012907:Smoking / Q000009:adverse effects*
keywords: DNA breaks; DNA repair; Gamma H2AX; Smoking; Smoking cessation; Syncytiotrophoblast