Tania Slatter,1 Lydia Park,1,2 Karyn Anderson,1,2 Viwa Lailai-Tasmania,2 Peter Herbison,3 William Clow,2 Janice Royds,1 Celia Devenish2 and Noelyn Hung1
1 Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin; 2 Women’s and Children’s Health, Obstetrics and Gynaecology, Dunedin School of Medicine, University of Otago, Dunedin; 3 Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin
Cigarette smoking during pregnancy continues to be an important public health problem in developed as well as developing nations. Tobacco smoking lowers birth weight, increases the risk of antepartum hemorrhage and abruption, and increases perinatal mortality. 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 smoke exposed placenta. Term placentae from women who smoked during their entire pregnancies (n=52), from those who had ceased smoking for at least four weeks before delivery (previous smokers, n=34), and from non-smoking women (n=150) were examined using the DNA double strand break marker phosphorylated gamma H2AX. The extent of DNA damage was assessed according to cell type, and additional markers applied, cell fate (apoptosis and DNA repair) and functional markers (human chorionic gonadotropin (hCG), human placental lactogen (hPL), and glucose transporter 1 (GLUT1)), to characterise the effect of the DNA damage on placental integrity.
Marked phosphorylated gamma H2AX positive cells occurred in the villous syncytiotrophoblast and syncytial knot nuclei in placentae from smokers (P < 0.001). Phosphorylated gamma H2AX foci did not co-localize with the DNA repair protein 53BP1, and damaged nuclei had a marked reduction in expression of hCG, hPL, and GLUT1. The DNA damage was associated with a reduced baby (P = 0.002) weight. In previous smokers, minimal DNA damage and baby weights similar to non-smoking mothers were found.
In summary, smoking during pregnancy was associated with marked double strand DNA break damage to the syncytiotrophoblast. We suggest smoking cessation is important to prevent additional DNA damage and to facilitate DNA repair. Future studies are aimed at investigating DNA damage as a cause of other low birth weights.